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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Cell. Infect. Microbiol.</journal-id>
<journal-title>Frontiers in Cellular and Infection Microbiology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Cell. Infect. Microbiol.</abbrev-journal-title>
<issn pub-type="epub">2235-2988</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fcimb.2024.1359432</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Cellular and Infection Microbiology</subject>
<subj-group>
<subject>Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Gut microbiota microbial metabolites in diabetic nephropathy patients: far to go</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Yu</surname>
<given-names>Jian-Xiu</given-names>
</name>
<uri xlink:href="https://loop.frontiersin.org/people/2609044"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chen</surname>
<given-names>Xin</given-names>
</name>
<uri xlink:href="https://loop.frontiersin.org/people/2366391"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zang</surname>
<given-names>Su-Gang</given-names>
</name>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chen</surname>
<given-names>Xi</given-names>
</name>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wu</surname>
<given-names>Yan-Yan</given-names>
</name>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Wu</surname>
<given-names>Li-Pei</given-names>
</name>
<xref ref-type="author-notes" rid="fn001">
<sup>*</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Xuan</surname>
<given-names>Shi-Hai</given-names>
</name>
<xref ref-type="author-notes" rid="fn001">
<sup>*</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
</contrib-group>
<aff id="aff1">
<institution>Medical Laboratory Department, Affiliated Dongtai Hospital of Nantong University</institution>, <addr-line>Dongtai, Jiangsu</addr-line>, <country>China</country>
</aff>
<author-notes>
<fn fn-type="edited-by">
<p>Edited by: Federico Biscetti, Agostino Gemelli University Polyclinic (IRCCS), Italy</p>
</fn>
<fn fn-type="edited-by">
<p>Reviewed by: Mithun Rudrapal, Technology and Research, India</p>
<p>Cosmin Mihai Vesa, University of Oradea, Romania</p>
<p>Junjun Li, Northwest A&amp;F University, China</p>
</fn>
<fn fn-type="corresp" id="fn001">
<p>*Correspondence: Shi-Hai Xuan, <email xlink:href="mailto:xsh.jyk@163.com">xsh.jyk@163.com</email>; Li-Pei Wu, <email xlink:href="mailto:wlp828414@163.com">wlp828414@163.com</email>
</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>08</day>
<month>05</month>
<year>2024</year>
</pub-date>
<pub-date pub-type="collection">
<year>2024</year>
</pub-date>
<volume>14</volume>
<elocation-id>1359432</elocation-id>
<history>
<date date-type="received">
<day>21</day>
<month>12</month>
<year>2023</year>
</date>
<date date-type="accepted">
<day>23</day>
<month>04</month>
<year>2024</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2024 Yu, Chen, Zang, Chen, Wu, Wu and Xuan</copyright-statement>
<copyright-year>2024</copyright-year>
<copyright-holder>Yu, Chen, Zang, Chen, Wu, Wu and Xuan</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<p>Diabetic nephropathy (DN) is one of the main complications of diabetes and a major cause of end-stage renal disease, which has a severe impact on the quality of life of patients. Strict control of blood sugar and blood pressure, including the use of renin&#x2013;angiotensin&#x2013;aldosterone system inhibitors, can delay the progression of diabetic nephropathy but cannot prevent it from eventually developing into end-stage renal disease. In recent years, many studies have shown a close relationship between gut microbiota imbalance and the occurrence and development of DN. This review discusses the latest research findings on the correlation between gut microbiota and microbial metabolites in DN, including the manifestations of the gut microbiota and microbial metabolites in DN patients, the application of the gut microbiota and microbial metabolites in the diagnosis of DN, their role in disease progression, and so on, to elucidate the role of the gut microbiota and microbial metabolites in the occurrence and prevention of DN and provide a theoretical basis and methods for clinical diagnosis and treatment.</p>
</abstract>
<kwd-group>
<kwd>diabetic nephropathy</kwd>
<kwd>gut microbiota</kwd>
<kwd>microbial metabolites</kwd>
<kwd>diagnosis and treatment</kwd>
<kwd>therapeutic strategies</kwd>
</kwd-group>
<counts>
<fig-count count="3"/>
<table-count count="2"/>
<equation-count count="0"/>
<ref-count count="96"/>
<page-count count="11"/>
<word-count count="5239"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-in-acceptance</meta-name>
<meta-value>Intestinal Microbiome</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec id="s1" sec-type="intro">
<label>1</label>
<title>Introduction</title>
<p>Diabetes is one of the most common chronic diseases worldwide, with prevalence and incidence rates increasing annually (<xref ref-type="bibr" rid="B500">Liu et&#xa0;al., 2021</xref>). It is estimated that by 2045, the absolute number of diabetes patients will increase by 46% (<xref ref-type="bibr" rid="B72">Sun H. et&#xa0;al., 2022</xref>). Diabetes can cause various serious and some life-threatening complications (<xref ref-type="bibr" rid="B56">Popoviciu et&#xa0;al., 2023</xref>). Diabetic nephropathy (DN) is one of the common microvascular complications, characterized by structural and functional damage to the kidneys (<xref ref-type="bibr" rid="B84">Wu and Huang, 2023</xref>). Clinical manifestations include massive proteinuria, hypertension, and edema, and it is one of the main causes of end-stage renal disease (ESRD) (<xref ref-type="bibr" rid="B83">Wu et&#xa0;al., 2023</xref>). At present, the diagnosis of DN depends on a decreased glomerular filtration rate (GFR) or increased urinary albumin excretion (UAE), but these changes are not unique to DN, and the diagnostic sensitivity and specificity in the preclinical stage of diabetic kidney damage are also limited (<xref ref-type="bibr" rid="B52">Oshima et&#xa0;al., 2021</xref>). At present, the treatment of DN mainly involves lifestyle guidance, metabolic therapy, and hypoglycemic and antihypertensive drugs to help patients slow down disease progression, thereby improving their quality of life (<xref ref-type="bibr" rid="B39">Liu P. et&#xa0;al., 2023</xref>). However, due to the complex pathogenesis of DN, no breakthrough progress has been made in the treatment of DN. Therefore, there is an urgency to search for new biomarkers generated by the pathogenesis of this disease to assist in its diagnosis, follow-up, treatment, and prognosis.</p>
<p>The human intestine harbors a variety of microorganisms, such as bacteria, fungi, and viruses, that are involved in the digestion of food, synthesis of essential vitamins and amino acids, elimination of pathogens, and clearance of toxins (<xref ref-type="bibr" rid="B15">Fernandes et&#xa0;al., 2022</xref>; <xref ref-type="bibr" rid="B85">Xiang et&#xa0;al., 2023</xref>). Through metagenomic sequencing analysis of human fecal samples, intestinal flora such as Bacteroidetes, Firmicutes, Proteobacteria, Actinobacteria, Verrucomicrobia, Cyanobacteria, and Spirochaetes have been identified (<xref ref-type="bibr" rid="B11">de Vos et&#xa0;al., 2022</xref>; <xref ref-type="bibr" rid="B7">Chen et&#xa0;al., 2023</xref>). Many studies have shown that changes in the abundance, diversity, and colonization location of the gut microbiota and alterations in serum metabolites can lead to DN, diabetic retinopathy, diabetic cardiovascular disease, and other complications (<xref ref-type="bibr" rid="B47">Lv et&#xa0;al., 2022</xref>; <xref ref-type="bibr" rid="B86">Xu et&#xa0;al., 2022</xref>). However, the specific role of the gut microbiota in DN is not yet fully understood. The recent emergence of the gut&#x2013;kidney axis theory has gradually revealed the correlation between gut microbiota and kidney diseases (<xref ref-type="bibr" rid="B53">Paul et&#xa0;al., 2022</xref>). The gut microbiota of DN patients is significantly different from that of healthy individuals, with a decrease in beneficial bacteria, such as <italic>Bifidobacterium</italic> and <italic>Lactobacillus</italic>, and an increase in the number of pathogenic bacteria, such as <italic>Enterobacter</italic> (<xref ref-type="bibr" rid="B23">Hu et&#xa0;al., 2020</xref>; <xref ref-type="bibr" rid="B5">Castillo-Rodriguez et&#xa0;al., 2018</xref>). An imbalance of the gut microbiota can lead to intestinal barrier damage, increased intestinal permeability, and accelerated transfer of microbial metabolites (such as indoxyl sulfate and p-cresyl sulfate) into the bloodstream, exacerbating kidney damage (<xref ref-type="bibr" rid="B7">Chen et&#xa0;al., 2023</xref>). Imbalance of the gut microbiota leads to metabolic endotoxemia, which induces chronic inflammation, short-chain fatty acid (SCFA) metabolism, oxidative stress, and other factors that affect the development of DN (<xref ref-type="bibr" rid="B32">Li J. et&#xa0;al., 2022</xref>). Correcting the imbalance of the gut microbiota may be a new target for treating DN.</p>
<p>We summarize the characteristics of the gut microbiota and metabolism in DN patients and discuss the application of gut microbiota and metabolism as biomarkers in DN, the role of the gut microbiota and metabolism in disease occurrence and development, and the application of microbial targeted therapy in DN.</p>
</sec>
<sec id="s2">
<label>2</label>
<title>Gut microbiota in DN patients</title>
<sec id="s2_1">
<label>2.1</label>
<title>Alteration of gut microbiota in DN Patients</title>
<p>The stability of the gut microbiota is closely related to host health and disease (<xref ref-type="bibr" rid="B20">Gebrayel et&#xa0;al., 2022</xref>). Normal gut microbiota contains a large number of bacteria such as <italic>Bacteroides</italic>, <italic>Bifidobacterium</italic>, and <italic>Lactobacillus</italic>. DN patients have imbalances in gut microbial composition, abundance, and diversity (<xref ref-type="bibr" rid="B27">Kikuchi et&#xa0;al., 2019</xref>). In 20 patients with type 2 diabetes (T2DM) and chronic kidney disease (CKD), the gut microbiota showed significantly higher levels of Proteobacteria, Verrucomicrobia, and Fusobacteria, which can produce lipopolysaccharides (LPS), compared with a health control group (<xref ref-type="bibr" rid="B61">Salguero et&#xa0;al., 2019</xref>). <xref ref-type="bibr" rid="B75">Tao et&#xa0;al. (2019)</xref> also found a high abundance of Proteobacteria in 14 confirmed cases of DN. <xref ref-type="bibr" rid="B4">Cai et&#xa0;al. (2022)</xref> also found high abundance of Proteobacteria in nondialysis-dependent DN patients. In addition, compared with healthy controls, the relative abundance of Ruminococcaceae, <italic>Butyricicoccus</italic>, and Lachnospiraceae, which produce SCFAs, was reduced in 31 nondialysis-dependent patients. <xref ref-type="bibr" rid="B63">Shang et&#xa0;al. (2022)</xref> found that the gut microbiota of 180 DN patients was enriched in Proteobacteria, Actinobacteriota, Synergistota, Euryarchaeota, Patescibacteria, Verrucomicrobiota, and Cyanobacteria, compared with healthy controls, while Bacteroidota and Bacteria unclassified were depleted. Compared with healthy controls, there was a decrease in the abundance of Firmicutes in 20 patients with DN, while Corynebacteriales and <italic>Eisenbergiella</italic>, as well as <italic>Ralstonia</italic>, were enriched (<xref ref-type="bibr" rid="B68">Song et&#xa0;al., 2021</xref>). In a study involving 60 patients with DN, there was no significant difference in the relative abundance of Actinobacteria and Firmicutes between the DN and healthy control group (<xref ref-type="bibr" rid="B9">Chen et&#xa0;al., 2021</xref>). That study confirmed that <italic>Alistipes</italic>, <italic>Bacteroides</italic>, <italic>Subdoligranulum</italic>, <italic>Lachnoclostridium</italic>, and <italic>Ruminococcus torques</italic> were detrimental factors in the development of DN (<xref ref-type="bibr" rid="B9">Chen et&#xa0;al., 2021</xref>). Compared with healthy controls, the gut microbiota of 43 patients diagnosed with stage 3 or 4 DN was enriched in <italic>Haemophilus</italic>, <italic>Escherichia&#x2013;Shigella</italic>, <italic>Megalococcus</italic>, <italic>Veillonella</italic>, and <italic>Anaerostipes</italic> (<xref ref-type="bibr" rid="B12">Du et&#xa0;al., 2021</xref>). Butyrate-producing bacteria (<italic>Clostridium</italic>, <italic>Ruminococcus</italic>, and <italic>Eubacterium</italic>) and potential probiotics (<italic>Lactobacillus</italic> and <italic>Bifidobacterium</italic>) were significantly reduced in T2DM and DN patients (<xref ref-type="bibr" rid="B89">Zhang L. et&#xa0;al., 2022</xref>). Compared with T2DM patients without kidney damage for &gt;10 years, 35 confirmed cases of DN showed a significant increase in the abundance of <italic>Christensenella</italic>, <italic>Clostridium-XIVa</italic>, <italic>Eisenbergiella</italic>, <italic>Flavonifractor</italic>, and <italic>Clostridium-XVIII</italic>, while the abundance of butyrate-producing bacteria, <italic>Bacillus</italic>, <italic>Enterobacter</italic>, <italic>Trichospira</italic>, and <italic>Roseburia</italic> was significantly reduced (<xref ref-type="bibr" rid="B44">Lu et&#xa0;al., 2023</xref>). Whole-genome analysis showed enrichment of seven bacterial species in the feces of 15 DN patients, including <italic>Alistipes shahii</italic>, <italic>Alistipes communis</italic>, <italic>Alistipes onderdonkii</italic>, <italic>Bacteroides intestinalis</italic>, <italic>Ruminococcus</italic> sp. <italic>strain JE7A12</italic>, and <italic>Odoribacter splanchnicus</italic> (<xref ref-type="bibr" rid="B28">Kim et&#xa0;al., 2023</xref>). However, whole-genome analysis of European women showed that <italic>A. shahii</italic> was higher in the healthy control group than in the diabetes group (<xref ref-type="bibr" rid="B13">Dwiyanto et&#xa0;al., 2021</xref>), which may be due to racial, dietary, and geographical differences (<xref ref-type="bibr" rid="B19">Gaulke and Sharpton, 2018</xref>). Differences in lifestyle, diet, race, and medical conditions may be the main factors leading to differences in gut microbiota expression in DN (<xref ref-type="bibr" rid="B13">Dwiyanto et&#xa0;al., 2021</xref>). Therefore, long-term, multicenter research is still needed to help us better understand the relationship between the gut microbiota and DN (<xref ref-type="table" rid="T1">
<bold>Table&#xa0;1</bold>
</xref>).</p>
<table-wrap id="T1" position="float">
<label>Table&#xa0;1</label>
<caption>
<p>Alteration of gut microbiota in DN.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="middle" align="left">Studies</th>
<th valign="middle" align="left">Subjects</th>
<th valign="middle" align="left">The variety of Gut microbiota</th>
<th valign="middle" align="left">Research method</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="middle" align="left">
<xref ref-type="bibr" rid="B68">Song et&#xa0;al. (2021)</xref>
</td>
<td valign="top" align="left">DN patients</td>
<td valign="middle" align="left">
<bold>Increased:</bold>
<break/>
<bold>At the genus level:</bold> <italic>Eisenbergiella</italic>, <italic>Ralstonia</italic>, <italic>Intestinimonas</italic>, <italic>Eubacterium_fissicatena_group</italic>
<break/>
<bold>Decreased:</bold>
<break/>
<bold>At the phylum levels:</bold> Firmicutes</td>
<td valign="top" align="left">High-throughput sequencing</td>
</tr>
<tr>
<td valign="middle" align="left">
<xref ref-type="bibr" rid="B9">Chen et&#xa0;al. (2021)</xref>
</td>
<td valign="top" align="left">DN patients</td>
<td valign="middle" align="left">
<bold>Increased:</bold>
<break/>
<bold>At the genus level:</bold> <italic>Alistipes</italic>, <italic>Bacteroides</italic>, <italic>Subdoligranulum</italic>, <italic>Lachnoclostridium</italic>, <italic>Parabacteroides</italic>
<break/>
<bold>Decreased:</bold> <italic>Klebsiella</italic>
</td>
<td valign="top" align="left">High-throughput sequencing</td>
</tr>
<tr>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B61">Salguero et&#xa0;al. (2019)</xref>
</td>
<td valign="top" align="left">DN patients</td>
<td valign="middle" align="left">I<bold>ncreased:</bold>
<break/>
<bold>At the phylum levels:</bold> Proteobacteria, Verrucomicrobi, Fusobacteria<break/>
<bold>Decreased:</bold>
<break/>
<bold>At the phylum levels:</bold> Firmicutes</td>
<td valign="top" align="left">16sRNA</td>
</tr>
<tr>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B75">Tao et&#xa0;al. (2019)</xref>
</td>
<td valign="top" align="left">DN patients</td>
<td valign="middle" align="left">
<bold>Increased:</bold>
<break/>
<bold>At the phylum levels:</bold> Proteobacteria<break/>
<bold>At the genus level:</bold> <italic>Coriobacteriaceae</italic>, <italic>Escherichia-Shigella</italic>
<break/>
<bold>Decreased:</bold>
<break/>
<bold>At the genus level:</bold> <italic>Prevotella_9</italic>
</td>
<td valign="top" align="left">16sRNA</td>
</tr>
<tr>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B12">Du et&#xa0;al. (2021)</xref>
</td>
<td valign="top" align="left">DN patients</td>
<td valign="middle" align="left">
<bold>Increased:</bold>
<break/>
<bold>At the phylum levels:</bold> Actinobacteria<break/>
<bold>At the class levels:</bold> Actinobacteria, Bacilli, Coriobacteriia, Negativicutes<break/>
<bold>At the order levels:</bold> Betaproteobacteriales, Bifidobacteriales, Coriobacteriales, Lactobacillales, Selenomonadales<break/>
<bold>At the family level:</bold>Atopobiaceae, Bifidobacteriaceae,<break/>Burkholderiaceae, Lactobacillaceae, Streptococcaceae, Tannerellaceae, Veillonellaceae<break/>
<bold>At the genus level:</bold>
<italic>Acidaminococcus</italic>,Lactobacillus, <italic>Megasphaera, Mitsuokella, Olsenella, Prevotella_7, Sutterella</italic>
<break/>
<bold>Decreased</bold>:<break/>
<bold>At the class levels:</bold> Alphaproteobacteria, Clostridia<break/>
<bold>At the order levels:</bold> Chitinophagales, Clostridiales,<break/>Rhizobiales, Xanthomonadales<break/>
<bold>At the family level:</bold>Chitinophagaceae, Lachnospiraceae, Rhodanobacteraceae<break/>
<bold>At the genus level:</bold>
<italic>Lachnoclostridium, Roseburia, Tyzzerella_3</italic>
</td>
<td valign="top" align="left">16S rDNA</td>
</tr>
<tr>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B89">Zhang L. et&#xa0;al. (2022)</xref>
</td>
<td valign="top" align="left">DN patients</td>
<td valign="top" align="left">
<bold>Increased:</bold>
<break/>
<bold>At the genus level:</bold>
<italic>Bacteroides, Bacteroides stercoris, Prevotella</italic> sp. <italic>MSX73, Barnesiella, Alistipes ihumii, Bacteroides stercoris CAG_120, Tannerella</italic> sp. <italic>CAG_51, Parabacteroides</italic> sp. <italic>20_3</italic>
<break/>
<bold>At the species level</bold>:<italic>Bacteroides stercoris, Bacteroides_eggerthii</italic>
<break/>
<bold>Decreased:</bold>
<break/>
<bold>At the genus level:</bold>
<italic>Prevotella, Lachnospira, oseburia intestinalis, Bacteroides plebeius CAG_211, Clostridium</italic> sp. <italic>CAG_768, Fusobacterium varium, Clostridium</italic> sp. <italic>26_22, Eubacterium</italic> sp. <italic>AF22_9, Roseburia</italic> sp. <italic>AM23_20</italic>
<break/>
<bold>At the species level</bold>:<italic>Bacteroides fragilis</italic>
</td>
<td valign="top" align="left">Metagenomic sequencing</td>
</tr>
<tr>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B44">Lu et&#xa0;al. (2023)</xref>
</td>
<td valign="top" align="left">DN patients</td>
<td valign="top" align="left">
<bold>Increased:</bold>
<break/>
<bold>At the genus level</bold>:<italic>Christensenella</italic>, <italic>Clostridium-XIVa</italic>, <italic>Eisenbergiella</italic>, <italic>Flavonifractor</italic>, <italic>Clostridium-XVIII</italic>
<break/>
<bold>Decreased:</bold>
<break/>
<bold>At the genus leve</bold>l:<italic>butyric-producing bacteria</italic>, <italic>Bacillus</italic>, <italic>Enterobacter</italic>, <italic>Trichospir</italic>a, <italic>Rosacella</italic>
</td>
<td valign="top" align="left">16S rDNA</td>
</tr>
<tr>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B28">Kim et&#xa0;al. (2023)</xref>
</td>
<td valign="top" align="left">DN patients</td>
<td valign="top" align="left">
<bold>Increased:</bold>
<break/>
<bold>At the species level</bold>:<italic>Alistipes onderdonkii</italic>, <italic>Alistipes shahii</italic>, <italic>Alistipes communis</italic>, <italic>Ruminococcus</italic> sp. strain JE7A12, <italic>Bacteroides intestinalis</italic>, and <italic>Odoribacter splanchnicus</italic>
</td>
<td valign="top" align="left">Metagenomic sequencing</td>
</tr>
<tr>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B4">Cai et&#xa0;al. (2022)</xref>
</td>
<td valign="top" align="left">DN patients</td>
<td valign="top" align="left">
<bold>Increased:</bold>
<break/>
<bold>At the phylum levels:</bold> Proteobacteria<break/>
<bold>At the class levels:</bold> &#x3b4;-proteobacteria, &#x3b3;-probacteria,<break/>
<bold>At the order levels:</bold> Pseudomonadales, Desulfovibrionales<break/>
<bold>At the family levels:</bold> Moraxellaceae, Desulfovibrionaceae<break/>
<bold>At the genus levels:</bold> <italic>Acinetobacter</italic>, <italic>Desulfovibrio</italic>,<break/>
<italic>Erysipelatoclostridium</italic>, <italic>Hungatella</italic>,<break/>
<bold>Decreased:</bold>
<break/>
<bold>At the phylum levels:</bold> Firmicutes<break/>
<bold>At the class levels:</bold> Clostridia<break/>
<bold>At the order levels:</bold> Clostridiales<break/>
<bold>At the family levels:</bold> Ruminococcaceae, Lachnospiraceae<break/>
<bold>At the genus levels:</bold> <italic>Ruminococcaceae_UCG_013</italic>, <italic>Lachnospira</italic>, <italic>Ruminococcaceae_UCG_014</italic>, <italic>Ruminococcaceae_UCG_003</italic>, <italic>Butyricicoccus</italic>, <italic>Lachnospiraceae_NK4A136_group</italic>, <italic>Eubacterium</italic>
</td>
<td valign="top" align="left">16S rDNA</td>
</tr>
<tr>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B87">Zhang B. et&#xa0;al. (2022)</xref>
</td>
<td valign="top" align="left">DN rats</td>
<td valign="top" align="left">
<bold>Increased:</bold>
<break/>
<bold>At the phylum levels:</bold> Actinobacteriota<break/>
<bold>At the class levels:</bold> Bacilli, Bacteroidia<break/>
<bold>At the order levels:</bold> Lactobacillales, Erysipelotrichales<break/>
<bold>At the family levels:</bold> <italic>Lactobacillaceae</italic>
<break/>
<bold>At the genus levels:</bold> <italic>NK4A214_group</italic>
<break/>
<bold>Decreased:</bold>
<break/>
<bold>At the phylum levels:</bold> Firmicutes<break/>
<bold>At the class levels:</bold> Clostridia<break/>
<bold>At the order levels:</bold> Clostridiales, Clostridia UCG-014<break/>
<bold>At the genus levels:</bold> <italic>Lachnospiraceae_NK4A136_group</italic>, <italic>Romboutsia</italic>
</td>
<td valign="top" align="left">16S rRNA</td>
</tr>
<tr>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B82">Wu et&#xa0;al. (2022)</xref>
</td>
<td valign="top" align="left">DN rats</td>
<td valign="top" align="left">
<bold>Increased:</bold>
<break/>
<bold>At the genus levels:</bold> <italic>Negativibacillus</italic>, <italic>Rikenella</italic>
<break/>
<bold>Decreased:</bold>
<break/>
<bold>At the genus levels:</bold> <italic>Akkermansia</italic>, <italic>Candidatus</italic>,<break/>
<italic>Erysipelatoclostridium</italic>, <italic>Ileibacterium</italic>
</td>
<td valign="top" align="left">16s rDNA</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="s2_2">
<label>2.2</label>
<title>The diagnostic and early warning value of microbiota in DN patients</title>
<p>The gut microbiota composition in DN patients undergoes significant changes, which can serve as biomarkers to differentiate clinical diagnosis or confirm DN through biopsy. For patients who are contraindicated for renal biopsy, gut microbiota testing may be a crucial alternative solution (<xref ref-type="bibr" rid="B64">Shang et&#xa0;al., 2020</xref>). Among the 14 DN patients confirmed by biopsy in Sichuan, China, the genus <italic>Prevotella_9</italic> accurately distinguished DM patients from healthy controls, with an area under the receiver operating characteristic curve (AUC) of 0.900. <italic>Escherichia&#x2013;Shigella</italic> and <italic>Prevotella_9</italic> also accurately differentiated DN patients confirmed by biopsy from DM patients, with an AUC of 0.860, which aided in the diagnosis of DN (<xref ref-type="bibr" rid="B75">Tao et&#xa0;al., 2019</xref>). However, Lu et&#xa0;al. found different results in 35 cases of DN confirmed by biopsy in Shanxi, China, where <italic>Flavonifractor</italic> (AUC=0.909) or <italic>Eisenbergiella</italic> (AUC=0.886) accurately identified DN and DM patients (<xref ref-type="bibr" rid="B44">Lu et&#xa0;al., 2023</xref>), which may be related to differences in northern and southern regions and dietary habits. <italic>Clostridium</italic> sp. CAG_768 (AUC=0.941), <italic>Bacteroides propionicifaciens</italic> (AUC=0.905), and <italic>Clostridium</italic> sp. CAG_715 (AUC=0.908) effectively differentiated DN patients from the healthy control group. Multiple linear regression analysis showed that the combined detection of <italic>Fusobacterium varium</italic>, Pseudomonadales, and <italic>Prevotella</italic> sp. MSX73 (AUC=0.889) distinguished T2DM from DN, and the AUC of bacterial biomarkers for T2DM and DN was higher than urinary albumin to creatinine ratio (ACR), albumin, and urinary creatinine ratio (<xref ref-type="bibr" rid="B89">Zhang L. et&#xa0;al., 2022</xref>). A random forest model constructed from the 25 least correlated microbial genera had an AUC of 0.972, indicating a high predictive ability of gut microbiota for DN (<xref ref-type="bibr" rid="B12">Du et&#xa0;al., 2021</xref>). These results suggest that the gut microbiota may be promising candidates for diagnosing DN. However, current research shows that the biomarkers of gut microbiota used for diagnosing DN vary among regions and races (<xref ref-type="bibr" rid="B19">Gaulke and Sharpton, 2018</xref>). Therefore, more clinical research is needed to explore the value of gut microbiota in DN diseases.</p>
</sec>
<sec id="s2_3">
<label>2.3</label>
<title>Gut microbiota associated with occurrence and development of DN</title>
<p>Many studies have shown significant changes in the gut microbiota of patients with DN. Dysbiosis of the gut microbiota in DN patients is associated with endotoxemia, inflammation (<xref ref-type="bibr" rid="B88">Zhang et&#xa0;al., 2021</xref>), intestinal barrier dysfunction (<xref ref-type="bibr" rid="B501">Xiong et&#xa0;al., 2019</xref>; <xref ref-type="bibr" rid="B73">Sun X. et&#xa0;al., 2022</xref>; <xref ref-type="bibr" rid="B86">Xu et&#xa0;al., 2022</xref>), and a decrease in beneficial bacteria that produce SCFAs (<xref ref-type="bibr" rid="B60">Sabatino et&#xa0;al., 2017</xref>). Pathogenic bacteria, such as <italic>Clostridium</italic>, <italic>Bacteroides</italic>, and <italic>Prevotella</italic>, can increase intestinal barrier permeability by producing toxins (<xref ref-type="bibr" rid="B10">Das et&#xa0;al., 2021</xref>). Increased intestinal permeability promotes the reabsorption of ammonia, and toxins produced by microbial metabolism (such as indoxyl sulfate and p-cresyl sulfate) are transferred into the blood, exacerbating kidney damage (<xref ref-type="bibr" rid="B47">Lv et&#xa0;al., 2022</xref>). Microbial dysbiosis, mainly characterized by an overgrowth of <italic>Proteus</italic>, is associated with increased inflammation in DN patients and a decrease in SCFA-producing bacteria, which is a key factor in the pathogenesis of DN (<xref ref-type="bibr" rid="B61">Salguero et&#xa0;al., 2019</xref>; <xref ref-type="bibr" rid="B70">Stavropoulou et&#xa0;al., 2021</xref>). In a DM rat model, excess acetate produced by dysbiosis of the gut microbiota induced early kidney damage by activating the renal renin&#x2013;angiotensin system (<xref ref-type="bibr" rid="B42">Lu et&#xa0;al., 2020</xref>). In experimental models of diabetes, microbiota-derived phenyl sulfate (PS) is associated with the progression of albuminuria (<xref ref-type="bibr" rid="B27">Kikuchi et&#xa0;al., 2019</xref>). Several recent studies have shown that regulating gut microbiota dysbiosis and improving intestinal barrier function can effectively reduce uremic toxin levels and serum proinflammatory mediators [such as tumor necrosis factor-&#x3b1;, interleukin (IL)-1&#x3b2;, and IL-18], thereby delaying the progression of DN (<xref ref-type="bibr" rid="B22">Han et&#xa0;al., 2023</xref>; <xref ref-type="bibr" rid="B65">Shi et&#xa0;al., 2023</xref>; <xref ref-type="bibr" rid="B77">Wang et&#xa0;al., 2023</xref>; <xref ref-type="bibr" rid="B83">Wu et&#xa0;al., 2023</xref>). These studies indicate that gut microbiota disorders play an essential role in the development of DN, and further exploration is needed to diagnose or treat DN by targeting the composition of gut microbiota (<xref ref-type="fig" rid="f1">
<bold>Figure&#xa0;1</bold>
</xref>).</p>
<fig id="f1" position="float">
<label>Figure&#xa0;1</label>
<caption>
<p>Gut microbiota associated with development of DN. (By Figdraw).</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fcimb-14-1359432-g001.tif"/>
</fig>
</sec>
</sec>
<sec id="s3">
<label>3</label>
<title>Microbial metabolites in DN patients</title>
<sec id="s3_1">
<label>3.1</label>
<title>Alteration of metabolites in DN patients</title>
<p>The interaction between gut microbiota and the host is mainly achieved through the production of metabolites, which play a key role in the pathogenesis of DN by producing a large number of metabolites (<xref ref-type="bibr" rid="B87">Zhang B. et&#xa0;al., 2022</xref>). <xref ref-type="bibr" rid="B91">Zhu et&#xa0;al. (2022)</xref> have shown that amino acid metabolism may play an important role in the progression of DM and DN. N-Acetylaspartic acid, L-valine, betaine, isoleucine, asparagine, and L-methionine are upregulated in patients with T2DM and DN, with a more significant increase in the latter. High levels of L-leucine and isoleucine are significantly correlated with rapid estimated GFR decline. Compared with healthy controls, DN patients have elevated levels of stearic acid, glutaric acid, 2-Amino-3-methylimidazo(4,5-f) quinoline, and L-proline, and decreased levels of 1,3,7-trimethyluric acid, homocarnosine, epinephrine, N-acetylputrescine, linoleic acid, and ephedrine (<xref ref-type="bibr" rid="B7">Chen et&#xa0;al., 2023</xref>). In addition, the abundance of SCFA metabolites, valerate, and caproate, are significantly decreased in the serum of DN patients (<xref ref-type="bibr" rid="B90">Zhong et&#xa0;al., 2022</xref>). Compared with healthy controls, 11 DN patients had significantly higher levels of leucine, isoleucine, methionine, valeric acid, and phenylacetate, and lower levels of acetate (<xref ref-type="bibr" rid="B28">Kim et&#xa0;al., 2023</xref>). <xref ref-type="bibr" rid="B35">Li Y. et&#xa0;al. (2022)</xref> have also found decreased levels of acetate in DN patients. Acetate is one of the main components of SCFAs, and the levels of other SCFAs components, propionate, and butyrate, are lower in DN patients compared with DM patients and healthy controls. This may be related to the decrease in SCFA-producing bacteria such as Ruminococcaceae, Lachnospiraceae, and Bacteroidaceae in the gut microbiota of DN patients (<xref ref-type="bibr" rid="B8">Chen T. et&#xa0;al., 2022</xref>). However, the construction of DN rat models showed that serum acetate levels increase in DM rats, accompanied by increased proteinuria, and <italic>in vitro</italic> experiments have confirmed that excessive acetate can cause tubulointerstitial damage (<xref ref-type="bibr" rid="B23">Hu X. et&#xa0;al., 2020</xref>; <xref ref-type="bibr" rid="B42">Lu et&#xa0;al., 2020</xref>). This difference may be related to different research subjects and diseases, and multicenter and cross-racial studies are needed to confirm the role of SCFAs in DN. Gut microbiota metabolites, such as PS and trimethylamine-N-oxide, are typical uremic toxins associated with podocyte injury (<xref ref-type="bibr" rid="B16">Fernandes et&#xa0;al., 2019</xref>) (<xref ref-type="table" rid="T2">
<bold>Table&#xa0;2</bold>
</xref>).</p>
<table-wrap id="T2" position="float">
<label>Table&#xa0;2</label>
<caption>
<p>Alteration of metabolic Changes in DN.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="middle" align="left">Studies</th>
<th valign="middle" align="left">Subjects</th>
<th valign="middle" align="left">The variety of Gut microbiota</th>
<th valign="middle" align="left">Research method</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B90">Zhong et&#xa0;al. (2022)</xref>
</td>
<td valign="top" align="left">DN patients</td>
<td valign="top" align="left">
<bold>Decreased:</bold> valerate, caproate</td>
<td valign="top" align="left">GC&#x2013;MS</td>
</tr>
<tr>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B1">Balint et&#xa0;al. (2023)</xref>
</td>
<td valign="top" align="left">DN patients</td>
<td valign="top" align="left">
<bold>Increased:</bold> indoxyl sulfate, Butenoylcarnitine, Sorbitol, Dimethyl Arginine<break/>
<bold>Decreased:</bold> arginine, hippuric acid</td>
<td valign="top" align="left">UHPLC-QTOF-ESI-MS Analysis</td>
</tr>
<tr>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B7">Chen et&#xa0;al. (2023)</xref>
</td>
<td valign="top" align="left">DN patients</td>
<td valign="top" align="left">
<bold>Increased:</bold> Stearic acid, Glutaric acid, 2-Amino-3-methylimidazo[4,5-f]quinoline, L-Proline<break/>
<bold>Decreased:</bold> 1,3,7-Trimethyluric acid, Homocarnosine, Epinephrine, N-Acetylputrescine, Linoleic acid, Ephedrine</td>
<td valign="top" align="left">UPLC-MS/MS</td>
</tr>
<tr>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B54">Peng et&#xa0;al. (2022)</xref>
</td>
<td valign="top" align="left">DN patients</td>
<td valign="top" align="left">
<bold>Increased:</bold> L-homocys, 3-sulfinylpyruvate, 2,3-Diketo-5-methythiopentyl-1-phosphate, dehydroalanine, L-cysteine, s-adenosyl-L-methionine, s-methyl-5-thio-D-ribose 1-phosphate, sn-Met-Cys-Ser, Asn-Cys-Pro-Pro<break/>
<bold>Decreased:</bold> Mercaptopyruvate,</td>
<td valign="top" align="left">untargeted LC/MS</td>
</tr>
<tr>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B28">Kim et&#xa0;al. (2023)</xref>
</td>
<td valign="top" align="left">DN patients</td>
<td valign="top" align="left">
<bold>Increased:</bold> valine, isoleucine, methionine, valerate, phenylacetate<break/>
<bold>Decreased:</bold> acetate</td>
<td valign="top" align="left">NMR spectroscopy</td>
</tr>
<tr>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B65">Shi et&#xa0;al. (2023)</xref>
</td>
<td valign="top" align="left">DN patients</td>
<td valign="top" align="left">
<bold>Increased:</bold> urinary metabolites propionic acid, oxoadipic acid, leucine, isovaleric acid, isobutyric acid, and indole-3-carboxylic acid</td>
<td valign="top" align="left">UPLC-MS/MS</td>
</tr>
<tr>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B87">Zhang B. et&#xa0;al. (2022)</xref>
</td>
<td valign="top" align="left">DN rats</td>
<td valign="top" align="left">
<bold>Increased:</bold> isomaltose, D-mannose, galactonic acid, citramalic acid, prostaglandin B2<break/>
<bold>Decreased:</bold> 3-(2-Hydroxyethyl) indole, 3-methylindole, indoleacrylic acid</td>
<td valign="top" align="left">UHPLC-QE-MS</td>
</tr>
<tr>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B76">Trifonova et&#xa0;al. (2022)</xref>
</td>
<td valign="top" align="left">DN patients</td>
<td valign="top" align="left">
<bold>Increased:</bold> L-arginine, L-proline, L-cysteine, citrulline, 4-guanidinobutanamide, N2-succinyl-L-ornithine, creatinine, citrulline, phosphoglycolic, 2-oxo-3-hydroxy-4-phosphobutanoic acids<break/>
<bold>Decreased:</bold> creatine, thiosulfate, thiocysteine, 3-sulfinylpyruvic acid</td>
<td valign="top" align="left">MS/MS</td>
</tr>
<tr>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B91">Zhu et&#xa0;al. (2022)</xref>
</td>
<td valign="top" align="left">DN patients</td>
<td valign="top" align="left">
<bold>Increased:</bold> N-acetylaspartic acid, L-valine, isoleucine, asparagine, betaine, L-methionine</td>
<td valign="top" align="left">LC&#x2013;MS</td>
</tr>
<tr>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B81">Winther et&#xa0;al. (2020)</xref>
</td>
<td valign="top" align="left">DN patients</td>
<td valign="top" align="left">
<bold>Increased:</bold> indoxyl sulphate, L-citrulline. Homocitrulline, L-kynurenine<break/>
<bold>Decreased:</bold> tryptophan</td>
<td valign="top" align="left">HPLC MS/MS</td>
</tr>
<tr>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B82">Wu et&#xa0;al. (2022)</xref>
</td>
<td valign="top" align="left">DN rats</td>
<td valign="top" align="left">
<bold>Increased:</bold> D-arabinose 5-phosphate, estrone 3-sulfate, L-theanine, 3&#x2032;-aenylic acid, adenosine 5&#x2032;-monophosphat<break/>
<bold>Decreased:</bold> aurohyocholic acid sodium salt, calcium phosphorylcholine chloride, tauro-alpha-muricholic, sodium salt, galactinol, phosphocholine</td>
<td valign="top" align="left">LC-MS</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="s3_2">
<label>3.2</label>
<title>The diagnostic and early warning value of metabolites in DN patients</title>
<p>Enrichment analysis has confirmed the involvement of the urea cycle, TCA cycle, glycolysis, and amino acid metabolism in the pathogenesis of DN. Meta-analysis of existing studies on DN identified lactate, hippuric acid, urea (in urine), and glutamine (in blood) as the most important noninvasive early diagnostic biomarkers (<xref ref-type="bibr" rid="B58">Roointan et&#xa0;al., 2021</xref>). Random forest model analysis showed that methionine and branched-chain amino acids (AUC=0.832) were among the most significant features, second only to estimated GFR and proteinuria, for distinguishing between DN patients and healthy controls (<xref ref-type="bibr" rid="B28">Kim et&#xa0;al., 2023</xref>). <xref ref-type="bibr" rid="B91">Zhu et&#xa0;al. (2022)</xref> confirmed that high levels of L-leucine (AUC=0.834) and isoleucine (AUC=0.932) have high diagnostic ability in distinguishing between DN and T2DM. Two oligopeptides, Asn-Met-Cys-Ser and Asn-Cys-Pro-Pro, were correlated with the severity of proteinuria, with AUC values of 0.8857 and 0.9963, respectively, making them potential biomarkers for differentiating the severity of DN (<xref ref-type="bibr" rid="B54">Peng et&#xa0;al., 2022</xref>). Through UHPLC-QTOF-ESI-MS analysis of serum and urine from 90 DN patients, arginine (AUC=0.500), L-acetylcarnitine (AUC=0.600), hippuric acid (AUC=0.700), indoxyl sulfate (AUC=0.600), butenoyl carnitine (AUC=0.600), and sorbitol (AUC=0.500) in serum, and p-cresylsulfate (AUC=0.800) in urine may serve as biomarkers for early DN (<xref ref-type="bibr" rid="B1">Balint et&#xa0;al., 2023</xref>). In the rat diabetic model constructed by <xref ref-type="bibr" rid="B27">Kikuchi et&#xa0;al. (2019)</xref>, high levels of phenyl PS were correlated with the severity of glomerular lesions, and a significant correlation between PS levels and ACR was subsequently demonstrated in human plasma. Receiver operating characteristic curve analysis showed that the combined use of PS with known factors increased the AUC from 0.713 to 0.751. These results indicate that the detection of metabolites is helpful for the early diagnosis of DN and assessment of disease severity, and can be used as a disease marker of DN and a target for future treatment.</p>
</sec>
<sec id="s3_3">
<label>3.3</label>
<title>Metabolism associated with occurrence and development of DN</title>
<p>Disturbance of the gut microbiota in DN patients can disrupt intestinal epithelial function, reduce beneficial SCFA production, and release gut-derived toxins (indoxyl sulfate) and inflammatory factors that can damage the kidneys (<xref ref-type="bibr" rid="B49">Meijers and Evenepoel, 2011</xref>). <xref ref-type="bibr" rid="B90">Zhong et&#xa0;al. (2022)</xref> confirmed that the decreased levels of gut microbiota metabolites valerate and caproate in DN patients are independently related to the progression of DN and can predict the progression of DN to ESRD (<xref ref-type="bibr" rid="B90">Zhong et&#xa0;al., 2022</xref>). Urinary metabolomics analysis revealed an increase in urinary myo-inositol concentration with progression of DN. It showed an additive effect in predicting the progression of ESRD in terms of serum creatinine and urinary protein-to-creatinine ratio (<xref ref-type="bibr" rid="B31">Kwon et&#xa0;al., 2023</xref>). In the pathways of cysteine and methionine metabolism, serum L-homocysteine and 3-sulfinyl pyruvic acid, as well as 2,3-diketomethylthiobutyryl-1-phosphate, were elevated in the DN group and increased with the progression of DN proteinuria, while mercapto-pyruvate was decreased in the DN group and further decreased in the heavy proteinuria group (<xref ref-type="bibr" rid="B54">Peng et&#xa0;al., 2022</xref>). The level of butyrate was decreased in DN patients, and supplementation with sodium butyrate increased autophagy by activating the AMPK/mTOR pathway in DN rats and improving kidney injury (<xref ref-type="bibr" rid="B4">Cai et&#xa0;al., 2022</xref>) (<xref ref-type="fig" rid="f2">
<bold>Figure&#xa0;2</bold>
</xref>). <xref ref-type="bibr" rid="B74">Tang et&#xa0;al. (2022)</xref> also found a decrease in butyrate levels in DN patients. In db/db mice, supplementation with butyrate can improve intestinal barrier function, activate the PI3K/Akt/mTOR pathway, suppress oxidative stress, and improve muscle atrophy caused by DN. However, some SCFAs have damaging effects on the kidneys. <xref ref-type="bibr" rid="B42">Lu et&#xa0;al. (2020)</xref> demonstrated that acetate derived from the gut microbiota activated G-protein-coupled receptor 43, which inhibits AMPK&#x3b1; activity, leading to dysregulation of cholesterol homeostasis and insulin signaling, and progression of DN. <xref ref-type="bibr" rid="B24">Hu Z. et&#xa0;al. (2020)</xref> also reached similar conclusions. These results indicate that the metabolites produced by DN patients in different metabolic pathways and different sample types will have different changes, and the role of various types of SCFAs in DN is still controversial. Therefore, more clinical and animal trials are needed to confirm the mechanism of metabolites in DN.</p>
<fig id="f2" position="float">
<label>Figure&#xa0;2</label>
<caption>
<p>Metabolism associated with development of DN. (By Figdraw).</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fcimb-14-1359432-g002.tif"/>
</fig>
</sec>
</sec>
<sec id="s4">
<label>4</label>
<title>Gut microbiota and microbial metabolites as therapeutic strategies in treatment of DN</title>
<sec id="s4_1">
<label>4.1</label>
<title>FMT</title>
<p>FMT is the transfer of gut microbiota from healthy individuals to patients with gut microbiota disorders, achieving the goal of rebuilding the homeostasis and diversity of the gut microbiota (<xref ref-type="bibr" rid="B2">Bian et&#xa0;al., 2022</xref>). In recent years, FMT has shown specific therapeutic effects in diseases such as migraine (<xref ref-type="bibr" rid="B26">Kapp&#xe9;ter et&#xa0;al., 2023</xref>), CKD (<xref ref-type="bibr" rid="B40">Liu et&#xa0;al., 2022</xref>), and <italic>Clostridium difficile</italic> infection (<xref ref-type="bibr" rid="B80">Wei et&#xa0;al., 2022</xref>). After FMT, DN mice showed significant relief of glomerulosclerosis and fibrosis, glomerular injury, basement membrane thickening, and mesangial proliferation, indicating that reconstruction of normal gut microbiota can alleviate DN. In addition, the levels of microbial-derived uremic solutes such as hippuric acid and cholic acid significantly decreased after FMT, indicating that FMT can affect the metabolism of DN mice by regulating microorganisms (<xref ref-type="bibr" rid="B63">Shang et&#xa0;al., 2022</xref>). FMT can reduce the destruction of cholesterol homeostasis, thereby improving the damage of renal tubulointerstitium in diabetic rats, suggesting that FMT may be a new strategy for the prevention and treatment of DN (<xref ref-type="bibr" rid="B24">Hu Z. et&#xa0;al., 2020</xref>). Another study showed that FMT improved the glomerular injury of streptozotocin (STZ)-induced diabetes in rats (<xref ref-type="bibr" rid="B43">Lu et&#xa0;al., 2021</xref>). In a T2DM mouse model, FMT reduced blood sugar, improved glucose tolerance and insulin resistance, and alleviated pancreatic island damage (<xref ref-type="bibr" rid="B78">Wang et&#xa0;al., 2020</xref>). These results indicate that FMT may be a new strategy for preventing and treating DN. Although FMT has some potential in the treatment of DN, it is mostly used in animal research, and more clinical trials are needed to confirm its therapeutic efficacy in DN patients, as well as the potential risks.</p>
</sec>
<sec id="s4_2">
<label>4.2</label>
<title>Diet</title>
<p>A high-fiber diet contributes to the reconstruction of intestinal microorganisms. After the induction of diabetes by a high-fiber diet and STZ, mice had reduced intestinal Firmicutes, increased Bacteroides, and increased Prevotella and Bifidobacterium, which produce SCFAs. This led to increase in concentration of SCFAs in serum and feces, preventing DN through the key pathways and genes involved in innate immunity, inflammation, and macrophage recruitment (<xref ref-type="bibr" rid="B34">Li et&#xa0;al., 2020</xref>). It also caused the generation of probiotics and a significant increase in <italic>Akkermansia muciniphila</italic>. A low carbohydrate diet can cause an increase in the abundance of SCFA-producing bacteria (<italic>Roseburis</italic>) and <italic>Ruminococcus</italic> (<xref ref-type="bibr" rid="B38">Liu K. et&#xa0;al., 2023</xref>). Intermittent fasting can improve metabolic diseases such as diabetes and cardiovascular disease by improving the composition of gut microbiota (<xref ref-type="bibr" rid="B41">Liu et&#xa0;al., 2020</xref>). Dietary polyphenols can stimulate the secretion of glucagon like peptide-1 (GLP-1) by intestinal L cells to improve glucose homeostasis (<xref ref-type="bibr" rid="B79">Wang et&#xa0;al., 2021</xref>). Dietary fiber can promote the production of SCFAs by intestinal bacteria, thereby enhancing insulin sensitivity and GLP-1 secretion (<xref ref-type="bibr" rid="B48">Mazhar et&#xa0;al., 2023</xref>). These results indicate that adjusting diet can prevent or delay DN by improving gut microbiota and related metabolites, which is worth further exploration.</p>
</sec>
<sec id="s4_3">
<label>4.3</label>
<title>Probiotics and postbiotics</title>
<p>Probiotics can promote human health by improving intestinal inflammation, regulating gut microbiota homeostasis, repairing cell damage, and regulating immunity, which is important in treating and preventing diseases (<xref ref-type="bibr" rid="B69">Staniszewski and Kordowska-Wiater, 2021</xref>; <xref ref-type="bibr" rid="B1000">Wolfe et&#xa0;al., 2023</xref>). A randomized, double-blind, placebo-controlled trial showed that the intake of probiotics can reduce symptomatic factors by producing SCFAs in the intestine and reducing the production of hydrogen peroxide free radicals, thereby reducing kidney inflammation and fibrosis (<xref ref-type="bibr" rid="B59">Ross, 2022</xref>). <italic>Lactobacillus reuteri</italic> GMNL&#x2010;263 can reduce hemoglobin A1c and blood glucose levels in rats with STZ-induced diabetes, and inhibit renal fibrosis caused by hyperglycemia (<xref ref-type="bibr" rid="B45">Lu et&#xa0;al., 2010</xref>). In a randomized controlled clinical trial, DN patients who consumed soy milk containing <italic>Lactobacillus plantarum</italic> A7 for 8 weeks showed significantly lower levels of cystatin C and inflammatory adipokine progranulin than in the soy milk group (<xref ref-type="bibr" rid="B51">Miraghajani et&#xa0;al., 2019</xref>). Supplementing probiotic <italic>Lactobacillus casei</italic> Zhang can improve SCFAs and nicotinamide metabolism, reduce renal injury, and delay renal function decline (<xref ref-type="bibr" rid="B92">Zhu et&#xa0;al., 2021</xref>). New compound probiotics (<italic>L. plantarum</italic> and <italic>Lactobacillus delbrueckii</italic> subsp. <italic>bulgaricus</italic>) can serve as adjuncts for metformin by increasing the production of butyrate, enhancing glucose metabolism in patients (<xref ref-type="bibr" rid="B36">Liang et&#xa0;al., 2023</xref>). In a mouse model of chronic renal failure induced by hyperglycemia, supplementing probiotics (including TYCA06, BLI-02, and VDD088) can alleviate deterioration of renal function in mice (<xref ref-type="bibr" rid="B30">Kuo et&#xa0;al., 2023</xref>). These studies suggest that probiotic supplementation is a potential therapy to improve kidney disease caused by diabetes-related metabolism.</p>
<p>Postbiotics come from metabolites or fragments of microorganisms (such as vitamins, lipids, secondary bile acids, bacteriocins, enzymes, extracellular polysaccharides, and SCFAs), and can also regulate gut microbiota without living microorganisms, resulting in lower intake risk (<xref ref-type="bibr" rid="B17">Gao J. et&#xa0;al., 2019</xref>; <xref ref-type="bibr" rid="B93">&#x17b;&#xf3;&#x142;kiewicz et&#xa0;al., 2020</xref>). <italic>Bifidobacterium longum</italic> 35624 can produce an extracellular polysaccharide, which prevents bacterial inflammation and promotes barrier function (<xref ref-type="bibr" rid="B62">Schiavi et&#xa0;al., 2016</xref>). When there is a sufficient amount of SCFAs in postbiotic formulations, it can improve epithelial barrier function and protect the body from damage induced by lipopolysaccharides (<xref ref-type="bibr" rid="B14">Feng et&#xa0;al., 2018</xref>). In a T2DM rat model treated with postbiotics, heat-inactivated <italic>Streptococcus thermophilus</italic> reduced fasting blood glucose levels, glucose tolerance, and insulin resistance, and increased the abundance of beneficial bacteria such as Ruminococcaceae and <italic>Veillonella</italic> (<xref ref-type="bibr" rid="B18">Gao X. et&#xa0;al., 2019</xref>). In a randomized double-blind parallel clinical trial, compared with the placebo group, oral pasteurization of <italic>Lactobacillus griffii</italic> CP2305 significantly increased the content of bifidobacteria in the intestines of the experimental group (<xref ref-type="bibr" rid="B71">Sugawara et&#xa0;al., 2016</xref>). The mechanism of action of postbiotics in intestinal diseases has not been fully elucidated, and more clinical trials are needed to verify their effectiveness.</p>
</sec>
<sec id="s4_4">
<label>4.4</label>
<title>Prebiotics and synbiotics</title>
<p>Prebiotics can regulate glucose metabolism by changing intestinal flora, thus slowing the progress of diabetic complications (<xref ref-type="bibr" rid="B3">Bock et&#xa0;al., 2021</xref>). Fructooligosaccharide (FOS) is a common prebiotic. FOS supplementation can improve the renal-related pathological changes caused by diabetes (<xref ref-type="bibr" rid="B55">Pengrattanachot et&#xa0;al., 2022</xref>). Similarly, FOS has a protective effect on the kidneys of rats with STZ-induced type 1 diabetes mellitus (T1DM) and improves diabetes-related metabolic abnormalities (<xref ref-type="bibr" rid="B21">Gobinath et&#xa0;al., 2010</xref>). Inulin type fructan regulates the gut microbiota of db/db mice, inducing bacterial enrichment that produces SCFAs, leading to an increase in acetate concentration that can improve glomerular injury and renal fibrosis (<xref ref-type="bibr" rid="B46">Luo et&#xa0;al., 2022</xref>). Prebiotic supplements can significantly reduce the concentration of uremic toxin cresol sulfate in patients with CKD (<xref ref-type="bibr" rid="B6">Chen L. et&#xa0;al., 2022</xref>), increase the level of SCFAs, improve intestinal permeability, and alleviate inflammation (<xref ref-type="bibr" rid="B66">Snelson et&#xa0;al., 2021</xref>). Resistant starch (RS) is a prebiotic that promotes the proliferation of beneficial bacteria, such as bifidobacteria and lactobacilli, leading to an increase in SCFA production and a decrease in uremic solutes produced by the microbial community (<xref ref-type="bibr" rid="B67">Snelson et&#xa0;al., 2019</xref>). In addition, RS can also alleviate polyuria symptoms and disruption of vitamin D homeostasis in rats with STZ-treated T1DM (<xref ref-type="bibr" rid="B29">Koh et&#xa0;al., 2014</xref>).</p>
<p>Synbiotics are a combination of prebiotics and probiotics. Supplementing synbiotics can improve the composition of intestinal microorganisms and delay the progression of diabetic complications (<xref ref-type="bibr" rid="B25">Jiang et&#xa0;al., 2022</xref>). Oral administration of synbiotics (containing <italic>Bifidobacterium lactis</italic> HN019, <italic>Lactobacillus rhamnosus HN001</italic>, and oligofructose) can increase the abundance of beneficial bacteria in the intestine, such as <italic>Clostridium sensu stricto 1</italic>, <italic>Bifidobacterium</italic>, <italic>Lactobacillus</italic>, and <italic>Collinsella</italic> (<xref ref-type="bibr" rid="B33">Li et&#xa0;al., 2023</xref>), as well as inhibitory effects on pathogens, increased production of SCFAs, and optimized colon function (<xref ref-type="bibr" rid="B57">Rinninella et&#xa0;al., 2019</xref>). In a T2DM model, an increase in SCFA-producing bacteria was observed in rats treated with synbiotics (Mangiferin and <italic>L. reuteri</italic> 1-12) (<xref ref-type="bibr" rid="B50">Meng et&#xa0;al., 2023</xref>). However, <xref ref-type="bibr" rid="B37">Liu F. et&#xa0;al. (2023)</xref> found that synbiotics cannot reduce serum creatinine levels in nondialysis patients, which may be related to different research subjects and pathogenic factors of kidney disease. At present, there is limited research on synbiotics in DN, and a large number of clinical studies are still needed to confirm their effects (<xref ref-type="fig" rid="f3">
<bold>Figure&#xa0;3</bold>
</xref>).</p>
<fig id="f3" position="float">
<label>Figure&#xa0;3</label>
<caption>
<p>The management and therapeutic strategies of DN based on gut microbiota. (By Figdraw).</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fcimb-14-1359432-g003.tif"/>
</fig>
</sec>
</sec>
<sec id="s5" sec-type="conclusions">
<label>5</label>
<title>Conclusion and prospects</title>
<p>In conclusion, we have summarized the composition of gut microbiota and serum and urine metabolites in patients with DN, elucidating the application of microbiota and microbial metabolites in diagnosing DN and their role in disease progression. Kidney damage in DN patients can lead to dysbiosis of the gut microbiota, and disruption of the microbiota can further impair kidney function by producing numerous metabolites, even causing irreversible lesions. Improving the stability of gut microbiota, enhancing glucose metabolism, and reducing the production of uremic toxins by adjusting the structure of the diet, FMT, and oral intake of probiotics/prebiotics can delay the progression of DN.</p>
<p>Despite numerous studies, our understanding of the relationship between DN and gut microbiota and metabolism is still in its early stages. Gut microbiota and microbial metabolites show different patterns in different stages of DN, and the underlying mechanisms are poorly understood. Currently, large-scale clinical studies are not conducted in multiple centers, both domestically and internationally. Evaluating gut microbiota and microbial metabolites as therapeutic strategies in the treatment of DN still requires extensive clinical research for validation. Future research should clarify the specific targets of the impact of gut microbiota and related metabolites on DN, providing new insights for diagnosing and treating DN.</p>
</sec>
<sec id="s6" sec-type="author-contributions">
<title>Author contributions</title>
<p>J-XY: Writing &#x2013; original draft. XinC: Writing &#x2013; original draft. S-GZ: Writing &#x2013; original draft. XiC: Writing &#x2013; original draft. Y-YW: Writing &#x2013; original draft. L-PW: Writing &#x2013; review &amp; editing. S-HX: Writing &#x2013; review &amp; editing.</p>
</sec>
</body>
<back>
<sec id="s7" sec-type="funding-information">
<title>Funding</title>
<p>The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by Yancheng Health Commission (Grant No.YK2023130).</p>
</sec>
<sec id="s8" sec-type="COI-statement">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="s9" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<fn-group>
<title>Abbreviations</title>
<fn fn-type="abbr">
<p>DN, diabetic nephropathy; FMT, Fecal microbiota transplantation; ESRD, end-stage renal disease; GFR, glomerular filtration rate; UAE, urinary albumin excretion; T2DM, type 2 diabetes; CKD, chronic kidney disease; LPS, lipopolysaccharides; HC, health control; SCFAs, short-chain fatty acids; AUC, the receiver operating characteristic curve; PS, phenyl sulfate; DM, diabetes mellitus; ACR, Urinary Albumin To Creatinine Ratio; STZ, streptozotocin; GLP-1, glucagon like peptide-1; FOS, Fructooligosaccharide; T1DM, type 1 diabetes mellitus; RS, Resistant starch; IL, interleukin.</p>
</fn>
</fn-group>
<ref-list>
<title>References</title>
<ref id="B93">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>&#x17b;&#xf3;&#x142;kiewicz</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Marzec</surname> <given-names>A.</given-names>
</name>
<name>
<surname>Ruszczy&#x144;ski</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Feleszko</surname> <given-names>W.</given-names>
</name>
</person-group> (<year>2020</year>). <article-title>Postbiotics-A step beyond pre-and probiotics</article-title>. <source>Nutrients</source> <volume>12</volume>, <elocation-id>2189</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3390/nu12082189</pub-id>
</citation>
</ref>
<ref id="B1">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Balint</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Socaciu</surname> <given-names>C.</given-names>
</name>
<name>
<surname>Socaciu</surname> <given-names>A. I.</given-names>
</name>
<name>
<surname>Vlad</surname> <given-names>A.</given-names>
</name>
<name>
<surname>Gadalean</surname> <given-names>F.</given-names>
</name>
<name>
<surname>Bob</surname> <given-names>F.</given-names>
</name>
<etal/>
</person-group>. (<year>2023</year>). <article-title>Quantitative, targeted analysis of gut microbiota derived metabolites provides novel biomarkers of early diabetic kidney disease in type 2 diabetes mellitus patients</article-title>. <source>Biomolecules</source> <volume>13</volume>, <elocation-id>1086</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3390/biom13071086</pub-id>
</citation>
</ref>
<ref id="B2">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Bian</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Liebert</surname> <given-names>A.</given-names>
</name>
<name>
<surname>Bicknell</surname> <given-names>B.</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>X. M.</given-names>
</name>
<name>
<surname>Huang</surname> <given-names>C.</given-names>
</name>
<name>
<surname>Pollock</surname> <given-names>C. A.</given-names>
</name>
</person-group> (<year>2022</year>). <article-title>Faecal microbiota transplantation and chronic kidney disease</article-title>. <source>Nutrients</source> <volume>14</volume>, <elocation-id>2528</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3390/nu14122528</pub-id>
</citation>
</ref>
<ref id="B3">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Bock</surname> <given-names>P. M.</given-names>
</name>
<name>
<surname>Telo</surname> <given-names>G. H.</given-names>
</name>
<name>
<surname>Ramalho</surname> <given-names>R.</given-names>
</name>
<name>
<surname>Sbaraini</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Leivas</surname> <given-names>G.</given-names>
</name>
<name>
<surname>Martins</surname> <given-names>A. F.</given-names>
</name>
<etal/>
</person-group>. (<year>2021</year>). <article-title>The effect of probiotics, prebiotics or synbiotics on metabolic outcomes in individuals with diabetes: a systematic review and meta-analysis</article-title>. <source>Diabetologia</source> <volume>64</volume>, <fpage>26</fpage>&#x2013;<lpage>41</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1007/s00125-020-05295-1</pub-id>
</citation>
</ref>
<ref id="B4">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Cai</surname> <given-names>K.</given-names>
</name>
<name>
<surname>Ma</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Cai</surname> <given-names>F.</given-names>
</name>
<name>
<surname>Huang</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Xiao</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Zhong</surname> <given-names>C.</given-names>
</name>
<etal/>
</person-group>. (<year>2022</year>). <article-title>Changes of intestinal microbiota in diabetic nephropathy and its effect on the progression of kidney injury</article-title>. <source>Endocrine</source> <volume>76</volume>, <fpage>294</fpage>&#x2013;<lpage>303</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1007/s12020-022-03002-1</pub-id>
</citation>
</ref>
<ref id="B5">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Castillo-Rodriguez</surname> <given-names>E.</given-names>
</name>
<name>
<surname>Fernandez-Prado</surname> <given-names>R.</given-names>
</name>
<name>
<surname>Esteras</surname> <given-names>R.</given-names>
</name>
<name>
<surname>Perez-Gomez</surname> <given-names>M. V.</given-names>
</name>
<name>
<surname>Gracia-Iguacel</surname> <given-names>C.</given-names>
</name>
<name>
<surname>Fernandez-Fernandez</surname> <given-names>B.</given-names>
</name>
<etal/>
</person-group>. (<year>2018</year>). <article-title>Impact of altered intestinal microbiota on Chronic Kidney Disease Progression</article-title>. <source>Toxins</source> <volume>10</volume>, <elocation-id>300</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3390/toxins10070300</pub-id>
</citation>
</ref>
<ref id="B7">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Chen</surname> <given-names>T. H.</given-names>
</name>
<name>
<surname>Cheng</surname> <given-names>C. Y.</given-names>
</name>
<name>
<surname>Huang</surname> <given-names>C. K.</given-names>
</name>
<name>
<surname>Ho</surname> <given-names>Y. H.</given-names>
</name>
<name>
<surname>Lin</surname> <given-names>J. C.</given-names>
</name>
</person-group> (<year>2023</year>). <article-title>Exploring the relevance between gut microbiota-metabolites profile and chronic kidney disease with distinct pathogenic factor</article-title>. <source>Microbiol. Spectr.</source> <volume>11</volume>, <elocation-id>e0280522</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.1128/spectrum.02805-22</pub-id>
</citation>
</ref>
<ref id="B8">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Chen</surname> <given-names>T.</given-names>
</name>
<name>
<surname>Shen</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Yu</surname> <given-names>Q.</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Wen</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Lu</surname> <given-names>H.</given-names>
</name>
<etal/>
</person-group>. (<year>2022</year>). <article-title>Purple red rice anthocyanins alleviate intestinal damage in cyclophosphamide-induced mice associated with modulation of intestinal barrier function and gut microbiota</article-title>. <source>Food. Chem.</source> <volume>397</volume>, <elocation-id>133768</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.foodchem.2022.133768</pub-id>
</citation>
</ref>
<ref id="B6">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Chen</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Shi</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Ma</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Shi</surname> <given-names>D.</given-names>
</name>
<name>
<surname>Qu</surname> <given-names>H.</given-names>
</name>
</person-group> (<year>2022</year>). <article-title>Effects of microbiota-driven therapy on circulating indoxyl sulfate and P-cresyl sulfate in patients with chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials</article-title>. <source>Adv. Nutr.</source> <volume>13</volume>, <fpage>1267</fpage>&#x2013;<lpage>1278</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1093/advances/nmab149</pub-id>
</citation>
</ref>
<ref id="B9">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Chen</surname> <given-names>W.</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Guo</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>Z.</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>Q.</given-names>
</name>
<name>
<surname>Yan</surname> <given-names>R.</given-names>
</name>
<etal/>
</person-group>. (<year>2021</year>). <article-title>The profile and function of gut microbiota in diabetic nephropathy</article-title>. <source>Diab. Metab. Syndr. Obes.</source> <volume>14</volume>, <fpage>4283</fpage>&#x2013;<lpage>4296</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.2147/DMSO.S320169</pub-id>
</citation>
</ref>
<ref id="B10">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Das</surname> <given-names>T.</given-names>
</name>
<name>
<surname>Jayasudha</surname> <given-names>R.</given-names>
</name>
<name>
<surname>Chakravarthy</surname> <given-names>S.</given-names>
</name>
<name>
<surname>Prashanthi</surname> <given-names>G. S.</given-names>
</name>
<name>
<surname>Bhargava</surname> <given-names>A.</given-names>
</name>
<name>
<surname>Tyagi</surname> <given-names>M.</given-names>
</name>
<etal/>
</person-group>. (<year>2021</year>). <article-title>Alterations in the gut bacterial microbiome in people with type 2 diabetes mellitus and diabetic retinopathy</article-title>. <source>Sci. Rep.</source> <volume>11</volume>, <fpage>2738</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41598-021-82538-0</pub-id>
</citation>
</ref>
<ref id="B11">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>de Vos</surname> <given-names>W. M.</given-names>
</name>
<name>
<surname>Tilg</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Van Hul</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Cani</surname> <given-names>P. D.</given-names>
</name>
</person-group> (<year>2022</year>). <article-title>Gut microbiome and health: mechanistic insights</article-title>. <source>Gut</source> <volume>71</volume>, <fpage>1020</fpage>&#x2013;<lpage>1032</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1136/gutjnl-2021-326789</pub-id>
</citation>
</ref>
<ref id="B12">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Du</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Xue</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Kong</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Lv</surname> <given-names>C.</given-names>
</name>
<name>
<surname>Li</surname> <given-names>Z.</given-names>
</name>
<etal/>
</person-group>. (<year>2021</year>). <article-title>Alteration of gut microbial profile in patients with diabetic nephropathy</article-title>. <source>Endocrine</source> <volume>73</volume>, <fpage>71</fpage>&#x2013;<lpage>84</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1007/s12020-021-02721-1</pub-id>
</citation>
</ref>
<ref id="B13">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Dwiyanto</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Hussain</surname> <given-names>M. H.</given-names>
</name>
<name>
<surname>Reidpath</surname> <given-names>D.</given-names>
</name>
<name>
<surname>Ong</surname> <given-names>K. S.</given-names>
</name>
<name>
<surname>Qasim</surname> <given-names>A.</given-names>
</name>
<name>
<surname>Lee</surname> <given-names>S. W. H.</given-names>
</name>
<etal/>
</person-group>. (<year>2021</year>). <article-title>Ethnicity influences the gut microbiota of individuals sharing a geographical location: a cross-sectional study from a middle-income country</article-title>. <source>Sci. Rep.</source> <volume>11</volume>, <fpage>2618</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41598-021-82311-3</pub-id>
</citation>
</ref>
<ref id="B14">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Feng</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>P.</given-names>
</name>
<name>
<surname>Huang</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>F.</given-names>
</name>
</person-group> (<year>2018</year>). <article-title>Short-chain fatty acids manifest stimulative and protective effects on intestinal barrier function through the inhibition of NLRP3 inflammasome and autophagy</article-title>. <source>Cell. Physiol. Biochem.</source> <volume>49</volume>, <fpage>190</fpage>&#x2013;<lpage>205</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1159/000492853</pub-id>
</citation>
</ref>
<ref id="B15">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Fernandes</surname> <given-names>M. R.</given-names>
</name>
<name>
<surname>Aggarwal</surname> <given-names>P.</given-names>
</name>
<name>
<surname>Costa</surname> <given-names>R. G. F.</given-names>
</name>
<name>
<surname>Cole</surname> <given-names>A. M.</given-names>
</name>
<name>
<surname>Trinchieri</surname> <given-names>G.</given-names>
</name>
</person-group> (<year>2022</year>). <article-title>Targeting the gut microbiota for cancer therapy</article-title>. <source>Nat. Rev. Cancer.</source> <volume>22</volume>, <fpage>703</fpage>&#x2013;<lpage>722</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41568-022-00513-x</pub-id>
</citation>
</ref>
<ref id="B16">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Fernandes</surname> <given-names>R.</given-names>
</name>
<name>
<surname>Viana</surname> <given-names>S. D.</given-names>
</name>
<name>
<surname>Nunes</surname> <given-names>S.</given-names>
</name>
<name>
<surname>Reis</surname> <given-names>F.</given-names>
</name>
</person-group> (<year>2019</year>). <article-title>Diabetic gut microbiota dysbiosis as an inflammaging and immunosenescence condition that fosters progression of retinopathy and nephropathy</article-title>. <source>Biochim. Biophys. Acta Mol. Basis. Dis.</source> <volume>1865</volume>, <fpage>1876</fpage>&#x2013;<lpage>1897</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.bbadis.2018.09.032</pub-id>
</citation>
</ref>
<ref id="B17">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Gao</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Li</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Wan</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Hu</surname> <given-names>T.</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Yang</surname> <given-names>S.</given-names>
</name>
<etal/>
</person-group>. (<year>2019</year>). <article-title>A novel postbiotic from <italic>lactobacillus rhamnosus</italic> GG with a beneficial effect on intestinal barrier function</article-title>. <source>Front. Microbiol.</source> <volume>10</volume>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fmicb.2019.00477</pub-id>
</citation>
</ref>
<ref id="B18">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Gao</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>F.</given-names>
</name>
<name>
<surname>Zhao</surname> <given-names>P.</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>R.</given-names>
</name>
<name>
<surname>Zeng</surname> <given-names>Q.</given-names>
</name>
</person-group> (<year>2019</year>). <article-title>Effect of heat-killed <italic>Streptococcus thermophilus</italic> on type 2 diabetes rats</article-title>. <source>Peer J.</source> <volume>7</volume>, <elocation-id>e7117</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.7717/peerj.7117</pub-id>
</citation>
</ref>
<ref id="B19">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Gaulke</surname> <given-names>C. A.</given-names>
</name>
<name>
<surname>Sharpton</surname> <given-names>T. J.</given-names>
</name>
</person-group> (<year>2018</year>). <article-title>The influence of ethnicity and geography on human gut microbiome composition</article-title>. <source>Nat. Med.</source> <volume>24</volume>, <fpage>1495</fpage>&#x2013;<lpage>1496</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41591-018-0210-8</pub-id>
</citation>
</ref>
<ref id="B20">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Gebrayel</surname> <given-names>P.</given-names>
</name>
<name>
<surname>Nicco</surname> <given-names>C.</given-names>
</name>
<name>
<surname>Al Khodor</surname> <given-names>S.</given-names>
</name>
<name>
<surname>Bilinski</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Caselli</surname> <given-names>E.</given-names>
</name>
<name>
<surname>Comelli</surname> <given-names>E. M.</given-names>
</name>
<etal/>
</person-group>. (<year>2022</year>). <article-title>Microbiota medicine: towards clinical revolution</article-title>. <source>J. Transl. Med.</source> <volume>20</volume>, <fpage>111</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1186/s12967-022-03296-9</pub-id>
</citation>
</ref>
<ref id="B21">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Gobinath</surname> <given-names>D.</given-names>
</name>
<name>
<surname>Madhu</surname> <given-names>A. N.</given-names>
</name>
<name>
<surname>Prashant</surname> <given-names>G.</given-names>
</name>
<name>
<surname>Srinivasan</surname> <given-names>K.</given-names>
</name>
<name>
<surname>Prapulla</surname> <given-names>S. G.</given-names>
</name>
</person-group> (<year>2010</year>). <article-title>Beneficial effect of xylo-oligosaccharides and fructo-oligosaccharides in streptozotocin-induced diabetic rats</article-title>. <source>Br. J. Nutr.</source> <volume>104</volume>, <fpage>40</fpage>&#x2013;<lpage>47</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1017/S0007114510000243</pub-id>
</citation>
</ref>
<ref id="B22">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Han</surname> <given-names>C.</given-names>
</name>
<name>
<surname>Shen</surname> <given-names>Z.</given-names>
</name>
<name>
<surname>Cui</surname> <given-names>T.</given-names>
</name>
<name>
<surname>Ai</surname> <given-names>S. S.</given-names>
</name>
<name>
<surname>Gao</surname> <given-names>R. R.</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>Y.</given-names>
</name>
<etal/>
</person-group>. (<year>2023</year>). <article-title>Yi-Shen-Hua-Shi granule ameliorates diabetic kidney disease by the &#x201c;gut-kidney axis&#x201d;</article-title>. <source>J. Ethnopharmacol.</source> <volume>307</volume>, <elocation-id>116257</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.jep.2023.116257</pub-id>
</citation>
</ref>
<ref id="B24">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Hu</surname> <given-names>Z. B.</given-names>
</name>
<name>
<surname>Lu</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>P. P.</given-names>
</name>
<name>
<surname>Lu</surname> <given-names>C. C.</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>J. X.</given-names>
</name>
<name>
<surname>Li</surname> <given-names>X. Q.</given-names>
</name>
<etal/>
</person-group>. (<year>2020</year>). <article-title>Dysbiosis of intestinal microbiota mediates tubulointerstitial injury in diabetic nephropathy via the disruption of cholesterol homeostasis</article-title>. <source>Theranostics</source> <volume>10</volume>, <fpage>2803</fpage>&#x2013;<lpage>2816</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.7150/thno.40571</pub-id>
</citation>
</ref>
<ref id="B23">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Hu</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Ouyang</surname> <given-names>S.</given-names>
</name>
<name>
<surname>Xie</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Gong</surname> <given-names>Z.</given-names>
</name>
<name>
<surname>Du</surname> <given-names>J.</given-names>
</name>
</person-group> (<year>2020</year>). <article-title>Characterizing the gut microbiota in patients with chronic kidney disease</article-title>. <source>Postgrad. Med.</source> <volume>132</volume>, <fpage>495</fpage>&#x2013;<lpage>505</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1080/00325481.2020.1744335</pub-id>
</citation>
</ref>
<ref id="B25">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Jiang</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Cai</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Shen</surname> <given-names>B.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>Q.</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>T.</given-names>
</name>
<name>
<surname>Zhou</surname> <given-names>X.</given-names>
</name>
</person-group> (<year>2022</year>). <article-title>Synbiotics and gut microbiota: new perspectives in the treatment of type 2 diabetes mellitus</article-title>. <source>Foods</source> <volume>11</volume>, <elocation-id>2438</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3390/foods11162438</pub-id>
</citation>
</ref>
<ref id="B26">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Kapp&#xe9;ter</surname> <given-names>&#xc1;.</given-names>
</name>
<name>
<surname>Sipos</surname> <given-names>D.</given-names>
</name>
<name>
<surname>Varga</surname> <given-names>A.</given-names>
</name>
<name>
<surname>Vigv&#xe1;ri</surname> <given-names>S.</given-names>
</name>
<name>
<surname>Halda-Kiss</surname> <given-names>B.</given-names>
</name>
<name>
<surname>P&#xe9;terfi</surname> <given-names>Z.</given-names>
</name>
</person-group> (<year>2023</year>). <article-title>Migraine as a disease associated with dysbiosis and possible therapy with fecal microbiota transplantation</article-title>. <source>Microorganisms</source> <volume>11</volume>, <elocation-id>2083</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3390/microorganisms11082083</pub-id>
</citation>
</ref>
<ref id="B27">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Kikuchi</surname> <given-names>K.</given-names>
</name>
<name>
<surname>Saigusa</surname> <given-names>D.</given-names>
</name>
<name>
<surname>Kanemitsu</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Matsumoto</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Thanai</surname> <given-names>P.</given-names>
</name>
<name>
<surname>Suzuki</surname> <given-names>N.</given-names>
</name>
<etal/>
</person-group>. (<year>2019</year>). <article-title>Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease</article-title>. <source>Nat. Commun.</source> <volume>10</volume>, <fpage>1835</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41467-019-09735-4</pub-id>
</citation>
</ref>
<ref id="B28">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Kim</surname> <given-names>J. E.</given-names>
</name>
<name>
<surname>Nam</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Park</surname> <given-names>J. I.</given-names>
</name>
<name>
<surname>Cho</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Lee</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Kim</surname> <given-names>H. E.</given-names>
</name>
<etal/>
</person-group>. (<year>2023</year>). <article-title>Gut microbial genes and metabolism for methionine and branched-chain amino acids in diabetic nephropathy</article-title>. <source>Microbiol. Spectr.</source> <volume>11</volume>, <elocation-id>e0234422</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.1128/spectrum.02344-22</pub-id>
</citation>
</ref>
<ref id="B29">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Koh</surname> <given-names>G. Y.</given-names>
</name>
<name>
<surname>Whitley</surname> <given-names>E. M.</given-names>
</name>
<name>
<surname>Mancosky</surname> <given-names>K.</given-names>
</name>
<name>
<surname>Loo</surname> <given-names>Y. T.</given-names>
</name>
<name>
<surname>Grapentine</surname> <given-names>K.</given-names>
</name>
<name>
<surname>Bowers</surname> <given-names>E.</given-names>
</name>
<etal/>
</person-group>. (<year>2014</year>). <article-title>Dietary resistant starch prevents urinary excretion of vitamin D metabolites and maintains circulating 25-hydroxycholecalciferol concentrations in Zucker diabetic fatty rats</article-title>. <source>J. Nutr.</source> <volume>144</volume>, <fpage>1667</fpage>&#x2013;<lpage>1673</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.3945/jn.114.198200</pub-id>
</citation>
</ref>
<ref id="B30">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Kuo</surname> <given-names>Y. W.</given-names>
</name>
<name>
<surname>Huang</surname> <given-names>Y. Y.</given-names>
</name>
<name>
<surname>Tsai</surname> <given-names>S. Y.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>J. Y.</given-names>
</name>
<name>
<surname>Lin</surname> <given-names>J. H.</given-names>
</name>
<name>
<surname>Syu</surname> <given-names>Z. J.</given-names>
</name>
<etal/>
</person-group>. (<year>2023</year>). <article-title>Probiotic formula ameliorates renal dysfunction indicators, glycemic levels, and blood pressure in a diabetic nephropathy mouse model</article-title>. <source>Nutrients</source> <volume>15</volume>, <elocation-id>2803</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3390/nu15122803</pub-id>
</citation>
</ref>
<ref id="B31">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Kwon</surname> <given-names>S.</given-names>
</name>
<name>
<surname>Hyeon</surname> <given-names>J. S.</given-names>
</name>
<name>
<surname>Jung</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Li</surname> <given-names>L.</given-names>
</name>
<name>
<surname>An</surname> <given-names>J. N.</given-names>
</name>
<name>
<surname>Kim</surname> <given-names>Y. C.</given-names>
</name>
<etal/>
</person-group>. (<year>2023</year>). <article-title>Urine myo-inositol as a novel prognostic biomarker for diabetic kidney disease: a targeted metabolomics study using nuclear magnetic resonance</article-title>. <source>Kidney. Res. Clin. Pract.</source> <volume>42</volume>, <fpage>445</fpage>&#x2013;<lpage>459</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.23876/j.krcp.22.152</pub-id>
</citation>
</ref>
<ref id="B34">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Li</surname> <given-names>Y. J.</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Kwan</surname> <given-names>T. K.</given-names>
</name>
<name>
<surname>Loh</surname> <given-names>Y. W.</given-names>
</name>
<name>
<surname>Singer</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>Y.</given-names>
</name>
<etal/>
</person-group>. (<year>2020</year>). <article-title>Dietary Fiber Protects against Diabetic Nephropathy through Short-Chain Fatty Acid-Mediated Activation of G Protein-Coupled Receptors GPR43 and GPR109A</article-title>. <source>J. Am. Soc Nephrol.</source> <volume>31</volume>, <fpage>1267</fpage>&#x2013;<lpage>1281</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1681/ASN.2019101029</pub-id>
</citation>
</ref>
<ref id="B33">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Li</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Hu</surname> <given-names>S.</given-names>
</name>
<name>
<surname>Yin</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Peng</surname> <given-names>X.</given-names>
</name>
<name>
<surname>King</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Li</surname> <given-names>L.</given-names>
</name>
<etal/>
</person-group>. (<year>2023</year>). <article-title>Effect of synbiotic supplementation on immune parameters and gut microbiota in healthy adults: a double-blind randomized controlled trial</article-title>. <source>Gut. Microbes</source> <volume>15</volume>, <elocation-id>2247025</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.1080/19490976.2023.2247025</pub-id>
</citation>
</ref>
<ref id="B32">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Li</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Lv</surname> <given-names>J. L.</given-names>
</name>
<name>
<surname>Cao</surname> <given-names>X. Y.</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>H. P.</given-names>
</name>
<name>
<surname>Tan</surname> <given-names>Y. J.</given-names>
</name>
<name>
<surname>Chu</surname> <given-names>T.</given-names>
</name>
<etal/>
</person-group>. (<year>2022</year>). <article-title>Gut microbiota dysbiosis as an inflammaging condition that regulates obesity-related retinopathy and nephropathy</article-title>. <source>Front. Microbiol.</source> <volume>13</volume>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fmicb.2022.1040846</pub-id>
</citation>
</ref>
<ref id="B35">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Li</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Qin</surname> <given-names>G. Q.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>W. Y.</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Gao</surname> <given-names>X. Q.</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>J. H.</given-names>
</name>
<etal/>
</person-group>. (<year>2022</year>). <article-title>Short chain fatty acids for the risk of diabetic nephropathy in type 2 diabetes patients</article-title>. <source>Acta Diabetol.</source> <volume>59</volume>, <fpage>901</fpage>&#x2013;<lpage>909</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1007/s00592-022-01870-7</pub-id>
</citation>
</ref>
<ref id="B36">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Liang</surname> <given-names>Z. W.</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>Q.</given-names>
</name>
<name>
<surname>Jiang</surname> <given-names>Q. Y.</given-names>
</name>
</person-group> (<year>2023</year>). <article-title>Effect of a novel compound probiotic on metabolic markers of type 2 diabetes mellitus</article-title>. <source>Chin. J. Microecol.</source> <volume>35</volume>, <fpage>943</fpage>&#x2013;<lpage>949</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.13381/j.cnki.cjm.202308011</pub-id>
</citation>
</ref>
<ref id="B41">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Liu</surname> <given-names>Z.</given-names>
</name>
<name>
<surname>Dai</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Shi</surname> <given-names>R.</given-names>
</name>
<name>
<surname>Hui</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Jin</surname> <given-names>X.</given-names>
</name>
<etal/>
</person-group>. (<year>2020</year>). <article-title>Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment</article-title>. <source>Front. Microbiol.</source> <volume>11</volume>, <fpage>855</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41467-020-14676-4</pub-id>
</citation>
</ref>
<ref id="B500">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Liu</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Cheng</surname> <given-names>Y. W.</given-names>
</name>
<name>
<surname>Shao</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Sun</surname> <given-names>S. H.</given-names>
</name>
<name>
<surname>Wu</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Song</surname> <given-names>Q. H.</given-names>
</name>
<etal/>
</person-group>. (<year>2021</year>). <article-title>Gut microbiota dysbiosis in Chinese children with type 1 diabetes mellitus: An observational study</article-title>. <source>World journal of gastroenterology</source> <volume>27</volume> (<issue>19</issue>), <page-range>2394&#x2013;2414</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.3748/wjg.v27.i19.2394</pub-id>
</citation>
</ref>
<ref id="B37">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Liu</surname> <given-names>F.</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Lv</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Lun</surname> <given-names>H.</given-names>
</name>
</person-group> (<year>2023</year>). <article-title>Effects of prebiotics, probiotics and synbiotics on serum creatinine in non-dialysis patients: a meta-analysis of randomized controlled trials</article-title>. <source>Ren. Fail.</source> <volume>45</volume>, <elocation-id>2152693</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.1080/0886022X.2022.2152693</pub-id>
</citation>
</ref>
<ref id="B38">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Liu</surname> <given-names>K.</given-names>
</name>
<name>
<surname>Xie</surname> <given-names>Z. Y.</given-names>
</name>
<name>
<surname>Huo</surname> <given-names>Y. J.</given-names>
</name>
<name>
<surname>Guo</surname> <given-names>R. R.</given-names>
</name>
<name>
<surname>Feng</surname> <given-names>P. H.</given-names>
</name>
<name>
<surname>Kang</surname> <given-names>Z. Q.</given-names>
</name>
</person-group> (<year>2023</year>). <article-title>Low-carbohydrate diet regulates intestinal microorganisms to improve glucose metabolism in patients with type 2 diabetes mellitus</article-title>. <source>Chin. J. Microecol.</source> <volume>35</volume>, <fpage>708</fpage>&#x2013;<lpage>712 + 716</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.13381/j.cnki.cjm.202306013</pub-id>
</citation>
</ref>
<ref id="B40">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Liu</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>P.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Li</surname> <given-names>Y.</given-names>
</name>
<etal/>
</person-group>. (<year>2022</year>). <article-title>Fecal microbiota transplantation restores normal fecal composition and delays Malignant development of mild chronic kidney disease in rats</article-title>. <source>Front. Microbiol.</source> <volume>13</volume>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fmicb.2022.1037257</pub-id>
</citation>
</ref>
<ref id="B39">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Liu</surname> <given-names>P.</given-names>
</name>
<name>
<surname>Zhu</surname> <given-names>W.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Ma</surname> <given-names>G.</given-names>
</name>
<name>
<surname>Zhao</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Li</surname> <given-names>P.</given-names>
</name>
</person-group> (<year>2023</year>). <article-title>Chinese herbal medicine and its active compounds in attenuating renal injury <italic>via</italic> regulating autophagy in diabetic kidney disease</article-title>. <source>Front. Endocrinol.</source> <volume>14</volume>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fendo.2023.1142805</pub-id>
</citation>
</ref>
<ref id="B43">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Lu</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>P. P.</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>J. X.</given-names>
</name>
<name>
<surname>Li</surname> <given-names>X. Q.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>G. H.</given-names>
</name>
<name>
<surname>Yuan</surname> <given-names>B. Y.</given-names>
</name>
<etal/>
</person-group>. (<year>2021</year>). <article-title>GPR43 deficiency protects against podocyte insulin resistance in diabetic nephropathy through the restoration of AMPK&#x3b1; activity</article-title>. <source>Theranostics</source> <volume>11</volume>, <fpage>4728</fpage>&#x2013;<lpage>4742</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.7150/thno.56598</pub-id>
</citation>
</ref>
<ref id="B42">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Lu</surname> <given-names>C. C.</given-names>
</name>
<name>
<surname>Hu</surname> <given-names>Z. B.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>R.</given-names>
</name>
<name>
<surname>Hong</surname> <given-names>Z. H.</given-names>
</name>
<name>
<surname>Lu</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>P. P.</given-names>
</name>
<etal/>
</person-group>. (<year>2020</year>). <article-title>Gut microbiota dysbiosis-induced activation of the intrarenal renin-angiotensin system is involved in kidney injuries in rat diabetic nephropathy</article-title>. <source>Acta Pharmacol. Sin.</source> <volume>41</volume>, <fpage>1111</fpage>&#x2013;<lpage>1118</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41401-019-0326-5</pub-id>
</citation>
</ref>
<ref id="B44">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Lu</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Ma</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Li</surname> <given-names>R.</given-names>
</name>
</person-group> (<year>2023</year>). <article-title>Alterations of gut microbiota in biopsy-proven diabetic nephropathy and a long history of diabetes without kidney damage</article-title>. <source>Sci. Rep.</source> <volume>13</volume>, <fpage>12150</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41598-023-39444-4</pub-id>
</citation>
</ref>
<ref id="B45">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Lu</surname> <given-names>Y. C.</given-names>
</name>
<name>
<surname>Yin</surname> <given-names>L. T.</given-names>
</name>
<name>
<surname>Chang</surname> <given-names>W. T.</given-names>
</name>
<name>
<surname>Huang</surname> <given-names>J. S.</given-names>
</name>
</person-group> (<year>2010</year>). <article-title>Effect of Lactobacillus reuteri GMNL-263 treatment on renal fibrosis in diabetic rats</article-title>. <source>J. Biosci. Bioeng.</source> <volume>110</volume>, <fpage>709</fpage>&#x2013;<lpage>715</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.jbiosc.2010.07.006</pub-id>
</citation>
</ref>
<ref id="B46">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Luo</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Luo</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Cai</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Fu</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Li</surname> <given-names>W.</given-names>
</name>
<name>
<surname>Shi</surname> <given-names>L.</given-names>
</name>
<etal/>
</person-group>. (<year>2022</year>). <article-title>Inulin-type fructans change the gut microbiota and prevent the development of diabetic nephropathy</article-title>. <source>Pharmacol. Res.</source> <volume>183</volume>, <elocation-id>106367</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.phrs.2022.106367</pub-id>
</citation>
</ref>
<ref id="B47">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Lv</surname> <given-names>Q.</given-names>
</name>
<name>
<surname>Li</surname> <given-names>Z.</given-names>
</name>
<name>
<surname>Sui</surname> <given-names>A.</given-names>
</name>
<name>
<surname>Yang</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Han</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Yao</surname> <given-names>R.</given-names>
</name>
</person-group> (<year>2022</year>). <article-title>The role and mechanisms of gut microbiota in diabetic nephropathy, diabetic retinopathy and cardiovascular diseases</article-title>. <source>Front. Microbiol.</source> <volume>13</volume>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fmicb.2022.977187</pub-id>
</citation>
</ref>
<ref id="B48">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Mazhar</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Zhu</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Qin</surname> <given-names>L.</given-names>
</name>
</person-group> (<year>2023</year>). <article-title>The Interplay of Dietary Fibers and intestinal microbiota afects Type 2 Diabetes by Generating Short-Chain Fatty Acids</article-title>. <source>Foods</source> <volume>12</volume>, <elocation-id>1023</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3390/foods12051023</pub-id>
</citation>
</ref>
<ref id="B49">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Meijers</surname> <given-names>B. K.</given-names>
</name>
<name>
<surname>Evenepoel</surname> <given-names>P.</given-names>
</name>
</person-group> (<year>2011</year>). <article-title>The gut-kidney axis: indoxyl sulfate, p-cresyl sulfate and CKD progression</article-title>. <source>Nephrol. Dial. Transpl.</source> <volume>26</volume>, <fpage>759</fpage>&#x2013;<lpage>761</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1093/ndt/gfq818</pub-id>
</citation>
</ref>
<ref id="B50">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Meng</surname> <given-names>F.</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>F.</given-names>
</name>
<name>
<surname>Meng</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>Q.</given-names>
</name>
<name>
<surname>Yang</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>W.</given-names>
</name>
<etal/>
</person-group>. (<year>2023</year>). <article-title>Effects of the synbiotic composed of mangiferin and <italic>Lactobacillus reuteri</italic> 1-12 on type 2 diabetes mellitus rats</article-title>. <source>Front. Microbiol.</source> <volume>14</volume>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fmicb.2023.1158652</pub-id>
</citation>
</ref>
<ref id="B51">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Miraghajani</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Zaghian</surname> <given-names>N.</given-names>
</name>
<name>
<surname>Dehkohneh</surname> <given-names>A.</given-names>
</name>
<name>
<surname>Mirlohi</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Ghiasvand</surname> <given-names>R.</given-names>
</name>
</person-group> (<year>2019</year>). <article-title>Probiotic soy milk consumption and renal function among type 2 diabetic patients with nephropathy: a randomized controlled clinical trial</article-title>. <source>Probio. Antimicrob. Proteins.</source> <volume>11</volume>, <fpage>124</fpage>&#x2013;<lpage>132</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1007/s12602-017-9325-3</pub-id>
</citation>
</ref>
<ref id="B52">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Oshima</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Shimizu</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Yamanouchi</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Toyama</surname> <given-names>T.</given-names>
</name>
<name>
<surname>Hara</surname> <given-names>A.</given-names>
</name>
<name>
<surname>Furuichi</surname> <given-names>K.</given-names>
</name>
<etal/>
</person-group>. (<year>2021</year>). <article-title>Trajectories of kidney function in diabetes: a clinicopathological update</article-title>. <source>Nat. Rev. Nephrol.</source> <volume>17</volume>, <fpage>740</fpage>&#x2013;<lpage>750</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41581-021-00462-y</pub-id>
</citation>
</ref>
<ref id="B53">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Paul</surname> <given-names>P.</given-names>
</name>
<name>
<surname>Kaul</surname> <given-names>R.</given-names>
</name>
<name>
<surname>Chaari</surname> <given-names>A.</given-names>
</name>
</person-group> (<year>2022</year>). <article-title>Renal health improvement in diabetes through microbiome modulation of the gut-kidney axis with biotics: A systematic and narrative review of randomized controlled trials</article-title>. <source>Int. J. Mol. Sci.</source> <volume>23</volume>, <elocation-id>14838</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3390/ijms232314838</pub-id>
</citation>
</ref>
<ref id="B54">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Peng</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Shao</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Feng</surname> <given-names>S.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>C.</given-names>
</name>
<etal/>
</person-group>. (<year>2022</year>). <article-title>Serum metabolomics benefits discrimination kidney disease development in type 2 diabetes patients</article-title>. <source>Front. Med.</source> <volume>9</volume>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fmed.2022.819311</pub-id>
</citation>
</ref>
<ref id="B55">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Pengrattanachot</surname> <given-names>N.</given-names>
</name>
<name>
<surname>Thongnak</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Lungkaphin</surname> <given-names>A.</given-names>
</name>
</person-group> (<year>2022</year>). <article-title>The impact of prebiotic fructooligosaccharides on gut dysbiosis and inflammation in obesity and diabetes related kidney disease</article-title>. <source>Food. Funct.</source> <volume>13</volume>, <fpage>5925</fpage>&#x2013;<lpage>5945</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1039/D1FO04428A</pub-id>
</citation>
</ref>
<ref id="B56">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Popoviciu</surname> <given-names>M. S.</given-names>
</name>
<name>
<surname>Paduraru</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Nutas</surname> <given-names>R. M.</given-names>
</name>
<name>
<surname>Ujoc</surname> <given-names>A. M.</given-names>
</name>
<name>
<surname>Yahya</surname> <given-names>G.</given-names>
</name>
<name>
<surname>Metwally</surname> <given-names>K.</given-names>
</name>
<etal/>
</person-group>. (<year>2023</year>). <article-title>Diabetes mellitus secondary to endocrine diseases: an update of diagnostic and treatment particularities</article-title>. <source>Int. J. Mol. Sci.</source> <volume>16</volume>, <elocation-id>12676</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3390/ijms241612676</pub-id>
</citation>
</ref>
<ref id="B57">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Rinninella</surname> <given-names>E.</given-names>
</name>
<name>
<surname>Raoul</surname> <given-names>P.</given-names>
</name>
<name>
<surname>Cintoni</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Franceschi</surname> <given-names>F.</given-names>
</name>
<name>
<surname>Miggiano</surname> <given-names>G. A. D.</given-names>
</name>
<name>
<surname>Gasbarrini</surname> <given-names>A.</given-names>
</name>
<etal/>
</person-group>. (<year>2019</year>). <article-title>What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases</article-title>. <source>Microorganisms</source> <volume>7</volume>, <elocation-id>14</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3390/microorganisms7010014</pub-id>
</citation>
</ref>
<ref id="B58">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Roointan</surname> <given-names>A.</given-names>
</name>
<name>
<surname>Gheisari</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Hudkins</surname> <given-names>K. L.</given-names>
</name>
<name>
<surname>Gholaminejad</surname> <given-names>A.</given-names>
</name>
</person-group> (<year>2021</year>). <article-title>Non-invasive metabolic biomarkers for early diagnosis of diabetic nephropathy: Meta-analysis of profiling metabolomics studies</article-title>. <source>Nutr. Metab. Cardiovasc. Dis.</source> <volume>31</volume>, <fpage>2253</fpage>&#x2013;<lpage>2272</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.numecd.2021.04.021</pub-id>
</citation>
</ref>
<ref id="B59">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Ross</surname> <given-names>P.</given-names>
</name>
</person-group> (<year>2022</year>). <article-title>Expression of concern: Metabolic and genetic response to probiotics supplementation in patients with diabetic nephropathy: a randomized, double-blind, placebo-controlled trial</article-title>. <source>Food. Funct.</source> <volume>13</volume>, <fpage>4229</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1039/D2FO90024F</pub-id>
</citation>
</ref>
<ref id="B60">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Sabatino</surname> <given-names>A.</given-names>
</name>
<name>
<surname>Regolisti</surname> <given-names>G.</given-names>
</name>
<name>
<surname>Cosola</surname> <given-names>C.</given-names>
</name>
<name>
<surname>Gesualdo</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Fiaccadori</surname> <given-names>E.</given-names>
</name>
</person-group> (<year>2017</year>). <article-title>Intestinal microbiota in type 2 diabetes and chronic kidney disease</article-title>. <source>Curr. Diab. Rep.</source> <volume>17</volume>, <fpage>16</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1007/s11892-017-0841-z</pub-id>
</citation>
</ref>
<ref id="B61">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Salguero</surname> <given-names>M. V.</given-names>
</name>
<name>
<surname>Al-Obaide</surname> <given-names>M. A. I.</given-names>
</name>
<name>
<surname>Singh</surname> <given-names>R.</given-names>
</name>
<name>
<surname>Siepmann</surname> <given-names>T.</given-names>
</name>
<name>
<surname>Vasylyeva</surname> <given-names>T. L.</given-names>
</name>
</person-group> (<year>2019</year>). <article-title>Dysbiosis of Gram-negative gut microbiota and the associated serum lipopolysaccharide exacerbates inflammation in type 2 diabetic patients with chronic kidney disease</article-title>. <source>Exp. Ther. Med.</source> <volume>18</volume>, <fpage>3461</fpage>&#x2013;<lpage>3469</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.3892/etm.2019.7943</pub-id>
</citation>
</ref>
<ref id="B62">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Schiavi</surname> <given-names>E.</given-names>
</name>
<name>
<surname>Gleinser</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Molloy</surname> <given-names>E.</given-names>
</name>
<name>
<surname>Groeger</surname> <given-names>D.</given-names>
</name>
<name>
<surname>Frei</surname> <given-names>R.</given-names>
</name>
<name>
<surname>Ferstl</surname> <given-names>R.</given-names>
</name>
<etal/>
</person-group>. (<year>2016</year>). <article-title>The surface-associated exopolysaccharide of bifidobacterium longum 35624 plays an essential role in dampening host proinflammatory responses and repressing local TH17 responses</article-title>. <source>Appl. Environ. Microbiol.</source> <volume>82</volume>, <fpage>7185</fpage>&#x2013;<lpage>7196</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1128/AEM.02238-16</pub-id>
</citation>
</ref>
<ref id="B63">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Shang</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Cui</surname> <given-names>W.</given-names>
</name>
<name>
<surname>Guo</surname> <given-names>R.</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>P.</given-names>
</name>
<name>
<surname>Yu</surname> <given-names>W.</given-names>
</name>
<etal/>
</person-group>. (<year>2022</year>). <article-title>The harmful intestinal microbial community accumulates during DKD exacerbation and microbiome-metabolome combined validation in a mouse model</article-title>. <source>Front. Endocrinol.</source> <volume>13</volume>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fendo.2022.964389</pub-id>
</citation>
</ref>
<ref id="B64">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Shang</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Ren</surname> <given-names>Z. G.</given-names>
</name>
<name>
<surname>Guo</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>R. X.</given-names>
</name>
<name>
<surname>Ren</surname> <given-names>Y. D.</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>H. Y.</given-names>
</name>
<etal/>
</person-group>. (<year>2020</year>). <article-title>Predictive power of gut microbiome in the clinical or pathological diagnosis of diabetic kidney disease</article-title>. <source>SSRN. Electr. J</source>. doi:&#xa0;<pub-id pub-id-type="doi">10.2139/ssrn.3722057</pub-id>
</citation>
</ref>
<ref id="B65">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Shi</surname> <given-names>R.</given-names>
</name>
<name>
<surname>Tao</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Tang</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Wu</surname> <given-names>C.</given-names>
</name>
<name>
<surname>Fei</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Ge</surname> <given-names>H.</given-names>
</name>
<etal/>
</person-group>. (<year>2023</year>). <article-title>Abelmoschus Manihot ameliorates the levels of circulating metabolites in diabetic nephropathy by modulating gut microbiota in non-obese diabetes mice</article-title>. <source>Microb. Biotechnol.</source> <volume>16</volume>, <fpage>813</fpage>&#x2013;<lpage>826</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1111/1751-7915.14200</pub-id>
</citation>
</ref>
<ref id="B66">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Snelson</surname> <given-names>M.</given-names>
</name>
<name>
<surname>de Pasquale</surname> <given-names>C.</given-names>
</name>
<name>
<surname>Ekinci</surname> <given-names>E. I.</given-names>
</name>
<name>
<surname>Coughlan</surname> <given-names>M. T.</given-names>
</name>
</person-group> (<year>2021</year>). <article-title>Gut microbiome, prebiotics, intestinal permeability and diabetes complications</article-title>. <source>Best. Pract. Res. Clin. Endocrinol. Metab.</source> <volume>35</volume>, <elocation-id>101507</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.beem.2021.101507</pub-id>
</citation>
</ref>
<ref id="B67">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Snelson</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Kellow</surname> <given-names>N. J.</given-names>
</name>
<name>
<surname>Coughlan</surname> <given-names>M. T.</given-names>
</name>
</person-group> (<year>2019</year>). <article-title>Modulation of the gut microbiota by resistant starch as a treatment of chronic kidney diseases: evidence of efficacy and mechanistic insights</article-title>. <source>Adv. Nutr.</source> <volume>10</volume>, <fpage>303</fpage>&#x2013;<lpage>320</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1093/advances/nmy068</pub-id>
</citation>
</ref>
<ref id="B68">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Song</surname> <given-names>D.</given-names>
</name>
<name>
<surname>Mi</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>C.</given-names>
</name>
</person-group> (<year>2021</year>). <article-title>Patterns of intestinal flora imbalance in diabetic kidney disease and type 2 diabetes based upon high-throughput sequencing</article-title>. <source>J. Clin. Nephrol.</source> <volume>21</volume>, <fpage>887</fpage>&#x2013;<lpage>894</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.3969/j.issn.1671-2390.2021.11.002</pub-id>
</citation>
</ref>
<ref id="B69">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Staniszewski</surname> <given-names>A.</given-names>
</name>
<name>
<surname>Kordowska-Wiater</surname> <given-names>M.</given-names>
</name>
</person-group> (<year>2021</year>). <article-title>Probiotic and potentially probiotic yeasts-characteristics and food application</article-title>. <source>Foods</source> <volume>10</volume>, <elocation-id>1306</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3390/foods10061306</pub-id>
</citation>
</ref>
<ref id="B70">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Stavropoulou</surname> <given-names>E.</given-names>
</name>
<name>
<surname>Kantartzi</surname> <given-names>K.</given-names>
</name>
<name>
<surname>Tsigalou</surname> <given-names>C.</given-names>
</name>
<name>
<surname>Konstantinidis</surname> <given-names>T.</given-names>
</name>
<name>
<surname>Romanidou</surname> <given-names>G.</given-names>
</name>
<name>
<surname>Voidarou</surname> <given-names>C.</given-names>
</name>
<etal/>
</person-group>. (<year>2021</year>). <article-title>Focus on the gut-kidney axis in health and disease</article-title>. <source>Front. Med.</source> <volume>7</volume>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fmed.2020.620102</pub-id>
</citation>
</ref>
<ref id="B71">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Sugawara</surname> <given-names>T.</given-names>
</name>
<name>
<surname>Sawada</surname> <given-names>D.</given-names>
</name>
<name>
<surname>Ishida</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Aihara</surname> <given-names>K.</given-names>
</name>
<name>
<surname>Aoki</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Takehara</surname> <given-names>I.</given-names>
</name>
<etal/>
</person-group>. (<year>2016</year>). <article-title>Regulatory effect of paraprobiotic Lactobacillus gasseri CP2305 on gut environment and function</article-title>. <source>Microb. Ecol. Health Dis.</source> <volume>27</volume>, <elocation-id>30259</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3402/mehd.v27.30259</pub-id>
</citation>
</ref>
<ref id="B73">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Sun</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Huang</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Zhu</surname> <given-names>S.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>S.</given-names>
</name>
<name>
<surname>Xu</surname> <given-names>Z.</given-names>
</name>
<etal/>
</person-group>. (<year>2022</year>). <article-title>Yishen qingli heluo granule ameliorates renal dysfunction in 5/6 nephrectomized rats by targeting gut microbiota and intestinal barrier integrity</article-title>. <source>Front. Pharmacol.</source> <volume>13</volume>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fphar.2022.858881</pub-id>
</citation>
</ref>
<ref id="B72">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Sun</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Saeedi</surname> <given-names>P.</given-names>
</name>
<name>
<surname>Karuranga</surname> <given-names>S.</given-names>
</name>
<name>
<surname>Pinkepank</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Ogurtsova</surname> <given-names>K.</given-names>
</name>
<name>
<surname>Duncan</surname> <given-names>B. B.</given-names>
</name>
<etal/>
</person-group>. (<year>2022</year>). <article-title>IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045</article-title>. <source>Diab. Res. Clin. Pract.</source> <volume>183</volume>, <elocation-id>109119</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.diabres.2021.109119</pub-id>
</citation>
</ref>
<ref id="B74">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Tang</surname> <given-names>G.</given-names>
</name>
<name>
<surname>Du</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Guan</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Jia</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Zhu</surname> <given-names>N.</given-names>
</name>
<name>
<surname>Shi</surname> <given-names>Y.</given-names>
</name>
<etal/>
</person-group>. (<year>2022</year>). <article-title>Butyrate ameliorates skeletal muscle atrophy in diabetic nephropathy by enhancing gut barrier function and FFA2-mediated PI3K/Akt/mTOR signals</article-title>. <source>Br. J. Pharmacol.</source> <volume>179</volume>, <fpage>159</fpage>&#x2013;<lpage>178</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1111/bph.15693</pub-id>
</citation>
</ref>
<ref id="B75">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Tao</surname> <given-names>S.</given-names>
</name>
<name>
<surname>Li</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Li</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Ren</surname> <given-names>Q.</given-names>
</name>
<name>
<surname>Shi</surname> <given-names>M.</given-names>
</name>
<etal/>
</person-group>. (<year>2019</year>). <article-title>Understanding the gut-kidney axis among biopsy-proven diabetic nephropathy, type 2 diabetes mellitus and healthy controls: an analysis of the gut microbiota composition</article-title>. <source>Acta Diabetol.</source> <volume>56</volume>, <fpage>581</fpage>&#x2013;<lpage>592</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1007/s00592-019-01316-7</pub-id>
</citation>
</ref>
<ref id="B76">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Trifonova</surname> <given-names>O. P.</given-names>
</name>
<name>
<surname>Maslov</surname> <given-names>D. L.</given-names>
</name>
<name>
<surname>Balashova</surname> <given-names>E. E.</given-names>
</name>
<name>
<surname>Lichtenberg</surname> <given-names>S.</given-names>
</name>
<name>
<surname>Lokhov</surname> <given-names>P. G.</given-names>
</name>
</person-group> (<year>2022</year>). <article-title>Potential plasma metabolite biomarkers of diabetic nephropathy: untargeted metabolomics study</article-title>. <source>J. Pers. Med.</source> <volume>12</volume>, <elocation-id>1889</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3390/jpm12111889</pub-id>
</citation>
</ref>
<ref id="B79">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wang</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Alkhalidy</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>D.</given-names>
</name>
</person-group> (<year>2021</year>). <article-title>The emerging role of polyphenols in the management of type 2 diabetes</article-title>. <source>Molecules</source> <volume>2</volume>, <elocation-id>703</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3390/molecules26030703</pub-id>
</citation>
</ref>
<ref id="B77">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wang</surname> <given-names>F.</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>C.</given-names>
</name>
<name>
<surname>Ren</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Li</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Yang</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Yu</surname> <given-names>Y.</given-names>
</name>
<etal/>
</person-group>. (<year>2023</year>). <article-title>Sanziguben polysaccharides improve diabetic nephropathy in mice by regulating gut microbiota to inhibit the TLR4/NF-&#x3ba;B/NLRP3 signalling pathway</article-title>. <source>Pharm. Biol.</source> <volume>61</volume>, <fpage>427</fpage>&#x2013;<lpage>436</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1080/13880209.2023.2174145</pub-id>
</citation>
</ref>
<ref id="B78">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wang</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Lu</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Yan</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Tian</surname> <given-names>S.</given-names>
</name>
<name>
<surname>Zheng</surname> <given-names>D.</given-names>
</name>
<name>
<surname>Leng</surname> <given-names>D.</given-names>
</name>
<etal/>
</person-group>. (<year>2020</year>). <article-title>Promising treatment for type 2 diabetes: fecal microbiota transplantation reverses insulin resistance and impaired islets</article-title>. <source>Front. Cell. Infect. Microbiol.</source> <volume>9</volume>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fcimb.2019.00455</pub-id>
</citation>
</ref>
<ref id="B80">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wei</surname> <given-names>S.</given-names>
</name>
<name>
<surname>Bahl</surname> <given-names>M. I.</given-names>
</name>
<name>
<surname>Baunwall</surname> <given-names>S. M. D.</given-names>
</name>
<name>
<surname>Dahlerup</surname> <given-names>J. F.</given-names>
</name>
<name>
<surname>Hvas</surname> <given-names>C. L.</given-names>
</name>
<name>
<surname>Licht</surname> <given-names>T. R.</given-names>
</name>
</person-group> (<year>2022</year>). <article-title>Gut microbiota differs between treatment outcomes early after fecal microbiota transplantation against recurrent <italic>Clostridioides difficile</italic> infection</article-title>. <source>Gut Microbes</source> <volume>14</volume>, <elocation-id>2084306</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.1080/19490976.2022.2084306</pub-id>
</citation>
</ref>
<ref id="B81">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Winther</surname> <given-names>S. A.</given-names>
</name>
<name>
<surname>Henriksen</surname> <given-names>P.</given-names>
</name>
<name>
<surname>Vogt</surname> <given-names>J. K.</given-names>
</name>
<name>
<surname>Hansen</surname> <given-names>T. H.</given-names>
</name>
<name>
<surname>Ahonen</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Suvitaival</surname> <given-names>T.</given-names>
</name>
<etal/>
</person-group>. (<year>2020</year>). <article-title>Gut microbiota profile and selected plasma metabolites in type 1 diabetes without and with stratification by albuminuria</article-title>. <source>Diabetologia</source> <volume>63</volume>, <fpage>2713</fpage>&#x2013;<lpage>2724</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1007/s00125-020-05260-y</pub-id>
</citation>
</ref>
<ref id="B1000">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wolfe</surname> <given-names>W.</given-names>
</name>
<name>
<surname>Xiang</surname> <given-names>Z.</given-names>
</name>
<name>
<surname>Yu</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Li</surname> <given-names>P.</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Yao</surname> <given-names>M.</given-names>
</name>
<etal/>
</person-group>. (<year>2023</year>). <article-title>The challenge of applications of probiotics in gastrointestinal diseases</article-title>. <source>Adv. Gut &amp; Microbiome Research.</source> <volume>2023</volume>, <fpage>10</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1155/2023/1984200</pub-id>
</citation>
</ref>
<ref id="B83">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wu</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Yang</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Gu</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Ni</surname> <given-names>Z.</given-names>
</name>
<name>
<surname>Mou</surname> <given-names>S.</given-names>
</name>
<etal/>
</person-group>. (<year>2023</year>). <article-title>Sodium glucose co-transporter 2 (SGLT2) inhibition via dapagliflozin improves diabetic kidney disease (DKD) over time associatied with increasing effect on the gut microbiota in db/db mice</article-title>. <source>Front. Endocrinol.</source> <volume>14</volume>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fendo.2023.1026040</pub-id>
</citation>
</ref>
<ref id="B82">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wu</surname> <given-names>C.</given-names>
</name>
<name>
<surname>Fei</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Xu</surname> <given-names>Q.</given-names>
</name>
<name>
<surname>Tao</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Zhou</surname> <given-names>Z.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>Y.</given-names>
</name>
<etal/>
</person-group>. (<year>2022</year>). <article-title>Interaction between plasma metabolomics and intestinal microbiome in db/db mouse, an animal model for study of type 2 diabetes and diabetic kidney disease</article-title>. <source>Metabolites</source> <volume>12</volume>, <elocation-id>775</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3390/metabo12090775</pub-id>
</citation>
</ref>
<ref id="B84">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wu</surname> <given-names>Q.</given-names>
</name>
<name>
<surname>Huang</surname> <given-names>F.</given-names>
</name>
</person-group> (<year>2023</year>). <article-title>LncRNA H19: a novel player in the regulation of diabetic kidney disease</article-title>. <source>Front. Endocrinol.</source> <volume>14</volume>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fendo.2023.1238981</pub-id>
</citation>
</ref>
<ref id="B85">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Xiang</surname> <given-names>Z.</given-names>
</name>
<name>
<surname>Wu</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Li</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Zheng</surname> <given-names>S.</given-names>
</name>
<name>
<surname>Wei</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Xu</surname> <given-names>X.</given-names>
</name>
</person-group> (<year>2023</year>). <article-title>Gut microbiota modulation: a viable strategy to address medical needs in hepatocellular carcinoma and liver transplantation</article-title>. <source>Engineering</source>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.eng.2022.12.012</pub-id>
</citation>
</ref>
<ref id="B501">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Xiong</surname> <given-names>C. Q.</given-names>
</name>
<name>
<surname>Zhou</surname> <given-names>H. C.</given-names>
</name>
<name>
<surname>Wu</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Guo</surname> <given-names>N. Z.</given-names>
</name>
</person-group> (<year>2019</year>). <article-title>The Protective Effects and the Involved Mechanisms of Tanshinone IIA on Sepsis-Induced Brain Damage in Mice</article-title>. <source>Inflammation</source>. <volume>42</volume> (<issue>1</issue>), <page-range>354&#x2013;364</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1007/s10753-018-0899-z</pub-id>
</citation>
</ref>
<ref id="B86">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Xu</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Ma</surname> <given-names>C.</given-names>
</name>
<name>
<surname>Hua</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Li</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Xiang</surname> <given-names>Z.</given-names>
</name>
<name>
<surname>Wu</surname> <given-names>J.</given-names>
</name>
</person-group> (<year>2022</year>). <article-title>CNS and CNS diseases in relation to their immune system</article-title>. <source>Front. Immunol.</source> <volume>13</volume>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fimmu.2022.1063928</pub-id>
</citation>
</ref>
<ref id="B88">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zhang</surname> <given-names>F.</given-names>
</name>
<name>
<surname>Qi</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Feng</surname> <given-names>Q.</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>B.</given-names>
</name>
<name>
<surname>Li</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>C.</given-names>
</name>
<etal/>
</person-group>. (<year>2021</year>). <article-title>HIPK2 phosphorylates HDAC3 for NF-&#x3ba;B acetylation to ameliorate colitis-associated colorectal carcinoma and sepsis</article-title>. <source>Proc. Natl. Acad. Sci. U.S.A.</source> <volume>118</volume>, <elocation-id>e2021798118</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.1073/pnas.2021798118</pub-id>
</citation>
</ref>
<ref id="B87">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zhang</surname> <given-names>B.</given-names>
</name>
<name>
<surname>Wan</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Zhou</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Zhao</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Ma</surname> <given-names>L.</given-names>
</name>
<etal/>
</person-group>. (<year>2022</year>). <article-title>Characteristics of serum metabolites and gut microbiota in diabetic kidney disease</article-title>. <source>Front. Pharmacol.</source> <volume>13</volume>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fphar.2022.872988</pub-id>
</citation>
</ref>
<ref id="B89">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zhang</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>Z.</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Zhao</surname> <given-names>L.</given-names>
</name>
<name>
<surname>Chu</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Li</surname> <given-names>H.</given-names>
</name>
<etal/>
</person-group>. (<year>2022</year>). <article-title>Alterations of the gut microbiota in patients with diabetic nephropathy</article-title>. <source>Microbiol. Spectr.</source> <volume>10</volume>, <elocation-id>e0032422</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.1128/spectrum.00324-22</pub-id>
</citation>
</ref>
<ref id="B90">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zhong</surname> <given-names>C.</given-names>
</name>
<name>
<surname>Bai</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>Q.</given-names>
</name>
<name>
<surname>Ma</surname> <given-names>Y.</given-names>
</name>
<name>
<surname>Li</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>J.</given-names>
</name>
<etal/>
</person-group>. (<year>2022</year>). <article-title>Gut microbial products valerate and caproate predict renal outcome among the patients with biopsy-confirmed diabetic nephropathy</article-title>. <source>Acta Diabetol.</source> <volume>59</volume>, <fpage>1469</fpage>&#x2013;<lpage>1477</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1007/s00592-022-01948-2</pub-id>
</citation>
</ref>
<ref id="B91">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zhu</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Bai</surname> <given-names>M.</given-names>
</name>
<name>
<surname>Xie</surname> <given-names>X.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>J.</given-names>
</name>
<name>
<surname>Weng</surname> <given-names>C.</given-names>
</name>
<name>
<surname>Dai</surname> <given-names>H.</given-names>
</name>
<etal/>
</person-group>. (<year>2022</year>). <article-title>Impaired amino acid metabolism and its correlation with diabetic kidney disease progression in type 2 diabetes mellitus</article-title>. <source>Nutrients</source> <volume>14</volume>, <elocation-id>3345</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3390/nu14163345</pub-id>
</citation>
</ref>
<ref id="B92">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zhu</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Cao</surname> <given-names>C.</given-names>
</name>
<name>
<surname>Wu</surname> <given-names>Z.</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>H.</given-names>
</name>
<name>
<surname>Sun</surname> <given-names>Z.</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>M.</given-names>
</name>
<etal/>
</person-group>. (<year>2021</year>). <article-title>The probiotic L. casei Zhang slows the progression of acute and chronic kidney disease</article-title>. <source>Cell. Metab.</source> <volume>33</volume>, <fpage>2091</fpage>&#x2013;<lpage>2093</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.cmet.2021.08.015</pub-id>
</citation>
</ref>
</ref-list>
</back>
</article>