Abstract
The gut microbiota critically influences patient responses to chemoradiotherapy through bidirectional interactions with host physiology, modulating both therapeutic efficacy and toxicity. Radiotherapy and chemotherapy disrupt microbial homeostasis, exacerbating intestinal damage, systemic inflammation, and immune dysfunction, while specific commensals and metabolites enhance treatment response via metabolic reprogramming, DNA repair regulation, and immune activation. Key mechanisms include microbiota-mediated TLR/NF-κB signaling, SCFA-dependent epigenetic modifications, and microbial enhancement of immune checkpoint inhibitors. Clinical interventions such as probiotics, fecal microbiota transplantation, and targeted antibiotics demonstrate potential to mitigate toxicity and overcome resistance. This review summarizes emerging evidence on how microbial dysbiosis induced by radiotherapy and chemotherapy exacerbates intestinal damage, systemic inflammation, and immune dysfunction, while specific commensals and metabolites enhance chemoradiotherapy response via metabolic reprogramming, DNA repair modulation, and immune activation. These findings underscore the gut microbiota as a critical determinant of chemoradiotherapy precision, offering actionable targets for microbiome-guided therapeutic optimization.
1 Introduction
The gut microbiota profoundly influences host responses to chemoradiotherapy by modulating immune pathways, DNA repair, and metabolic activity (, ). Anticancer treatments often induce dysbiosis—marked by reduced Bifidobacterium and Lactobacillus and expansion of pathogens like enterotoxigenic Bacteroides fragilis—which exacerbates mucosal damage, inflammation, and therapeutic toxicity (). In contrast, specific microbes enhance treatment efficacy (). For instance, Bacteroides vulgatus promotes DNA repair in tumor cells, impacting chemoradiation outcomes, while Lactobacillus rhamnosus improves radioprotection via the TLR2–ROS–Nrf2 axis (–). Microbial metabolites such as short-chain fatty acids (SCFAs) regulate histone deacetylase activity and enhance immune activation, thereby potentiating antitumor responses (, ).
Mechanistically, microbial signaling through TLR/NF-κB pathways, epigenetic modifications, and metabolic reprogramming affects both tumor biology and treatment response (). Certain Gammaproteobacteria expressing cytidine deaminase inactivate gemcitabine, inducing resistance (), while Lactobacillus acidophilus enhances oxaliplatin efficacy by stimulating macrophage ROS production (). Furthermore, Bifidobacterium species increase CD8+ T cell infiltration and synergize with PD-L1 inhibitors, whereas Bacteroides fragilis supports CTLA-4 blockade via Th1 polarization (, ). Interventions such as probiotics, fecal microbiota transplantation (FMT), and targeted antibiotics offer potential to restore microbial balance, mitigate toxicity, and enhance therapeutic precision (). This review summarizes the microbiome–therapy interactions and their translational implications in oncology, with a focus on molecular pathways governed by microbial metabolites, to inform microbiome-targeted strategies for optimizing cancer treatment outcomes.
2 Gut microbiota in tumor progression
Advanced culture-independent techniques, including metagenomic and 16S rRNA sequencing, facilitate comprehensive microbial characterization (). Germ-free animal and FMT studies underscore the microbiota’s dual roles: symbiotic strains restrain tumorigenesis, whereas dysbiosis fosters oncogenic progression (). Reduced bacterial diversity heightens breast cancer susceptibility, with antibiotic exposure disrupting estrogen homeostasis and amplifying HER-2/neu-driven tumorigenesis (). Clinically, elevated fecal Blautia abundance associates with advanced histopathological stages (). Probiotic administration mitigates Th17 responses, enhances regulatory T cell (Treg) activity, and inhibits hepatocellular carcinoma via IL-6 and TNF-α suppression (, ). The SCFAs butyrate mediates antitumor activity by inhibiting histone deacetylases (HDACs) and stimulating GPR109A signaling (, ). Integrated multi-omics, especially metabolomics, reshape understanding of microbiota–cancer interactions (). Metatranscriptomics reveals stress-responsive microbial genes governing DNA repair and immunometabolic adaptation during therapy (), while metabolomics identifies bioactive metabolites influencing epithelial barrier integrity (). Together, these approaches provide high-resolution insight into host–microbiome–therapy dynamics, advancing predictive biomarker discovery and precision-targeted interventions.
Microbial ligands such as lipopolysaccharides (LPS), peptidoglycan, and bacterial CpG-DNA serve as MAMPs that engage PRRs like Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD) proteins (, ). For instance, LPS derived from Gram-negative bacteria binds TLR4 on dendritic cells, triggering MyD88-dependent signaling cascades that activate NF-κB, leading to transcription of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α (, ). Simultaneously, IL-6 and IL-23 promote STAT3 phosphorylation in T cells, favoring differentiation into Th17 cells over Tregs (). In contrast, certain symbionts like Bacteroides fragilis produce polysaccharide A, which activates TLR2 and promotes IL-10–secreting regulatory T cells, suggesting that microbial pathway engagement can have dual outcomes depending on context and composition (). Disrupted crosstalk between microbial components and pattern recognition receptors (PRRs) is a pivotal driver of malignant transformation (). Microbial-associated molecular patterns (MAMPs) engage Toll-like receptors (TLRs), activating Ca²+/calcineurin-NFAT signaling to stimulate cellular proliferation (). Aberrant TLR4 expression promotes oncogenesis in pulmonary, hepatic, and colorectal cancers, whereas TLR2 upregulation contributes to gastric carcinogenesis (–). Cooperative NF-κB/STAT3 signaling suppresses apoptosis via NF-κB while promoting angiogenesis and immune evasion through STAT3-dependent VEGF and PD-L1 expression (–), underscoring the microbiota’s dual regulatory role in tumor–immune modulation.
3 Interplay between intestinal microbiota and radiotherapy
3.1 Gut microbiota in radiotherapy response
Radiotherapy disrupts gut microbiota by damaging epithelial DNA, reducing stem cells, and impairing mucus barriers, leading to decreased diversity (Bacteroidetes/Firmicutes imbalance), pathogenic overgrowth (Enterobacteriaceae), and loss of beneficial taxa (Bifidobacterium) (). These alterations exacerbate radiation-induced toxicity. Specifically, diminished SCFA production impairs metabolism, while immune dysfunction emerges through elevated IL-1β/TNF-α and a Th17/Treg imbalance (–). Moreover, microbial composition has predictive value. Patients with richer microbiota profiles respond better to lower radiation doses. In contrast, individuals with dysbiotic microbiota often require intensified regimens, highlighting the microbiome’s potential as a biomarker for personalized dosing (–). Clinical evidence further supports this. Fecal microbial gene signatures correlate with the severity of radiation-induced intestinal injury, enabling real-time stratification of patients undergoing pelvic irradiation (). Notably, pelvic radiotherapy elevates Blautia levels, which associates with compromised gut barrier function, electrolyte dysregulation, and diarrhea. Interventions such as probiotic supplementation (Lactobacillus/Bifidobacterium) mitigate enteritis by reinforcing tight junctions and suppressing TLR4-NF-κB signaling (, ). FMT has also demonstrated efficacy in reestablishing microbial equilibrium, promoting mucosal healing, and overcoming radioresistance (). Mechanistically, specific strains such as Lactobacillus rhamnosus enhance radiotherapy efficacy by activating the TLR2-ROS-Nrf2 pathway. This augments antioxidant responses and facilitates CD8+ T cell recruitment to the tumor site (). Together, these insights elucidate the molecular mechanisms governing microbiota-radiotherapy interactions, providing a foundation for microbiome-informed precision radiation oncology.
3.2 Microbial dysbiosis and barrier dysfunction in radiotherapy
Radiation therapy profoundly perturbs gastrointestinal microbial homeostasis through direct DNA damage to crypt stem cells induced by ionizing radiation. This triggers p53-mediated apoptosis, compromises barrier integrity (), and initiates a pathological cascade. Reduced Paneth cell secretion of antimicrobial peptides weakens mucosal defense, allowing expansion of opportunistic taxa (Bacteroidaceae, Lactobacillaceae) while depleting Clostridiaceae, a key source of SCFAs (). The ensuing dysbiosis activates dendritic cells via TLR4–NF-κB signaling, driving excessive release of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and reinforcing a cycle of radiation-induced epithelial injury, microbial imbalance, and inflammation (). In Wistar rats, whole-body irradiation elicited dose-dependent microbiota shifts, with increased Bacteroidaceae and Lactobacillaceae 16S rRNA alongside Clostridiaceae depletion, suggesting this signature as a potential biomarker of radiation exposure (). Overgrowth of pathobionts further compromises epithelial permeability, enabling bacterial translocation and systemic inflammation that underlie post-radiotherapy complications such as diarrhea and electrolyte imbalance (). Notably, dysbiosis and barrier dysfunction act bidirectionally: reduced SCFAs impair epithelial regeneration, while persistent injury exacerbates microbial disruption, establishing a vicious cycle of sustained tissue damage (). These findings highlight microbial modulation as a promising therapeutic approach for radiation enteritis, with strategies targeting Clostridiaceae restoration and TLR4-NF-κB pathway inhibition emerging as critical interventions ().
3.3 Radiation-triggered systemic antitumor immunity shaped by gut microbiota
The abscopal phenomenon in radiotherapy depends on radiation-induced antigen exposure, cross-priming by dendritic cells, and subsequent systemic T-cell activation (). In TSA breast carcinoma and MCA38 colon adenocarcinoma models, the combined fractionated radiation and CTLA-4 inhibition synergistically enhance systemic antitumor immunity, emphasizing the critical role of adaptive immune responses (). The intestinal microbiome significantly influences immune function through gut-associated lymphoid tissue (GALT). Studies in axenic mice reveal underdeveloped Peyer’s patches containing diminished CD4+ T lymphocyte populations and decreased IgA-secreting B cells, resulting in compromised tumor surveillance (, , ). In contrast, colonization with segmented filamentous bacteria (SFB) potentiates antigen presentation through TLR4 stimulation and modified bile acid metabolism (). Secondary bile acids, such as deoxycholic acid and lithocholic acid, act through the farnesoid X receptor (FXR) and G-protein-coupled bile acid receptor 1 (TGR5) to modulate intestinal immunity and regulate inflammation, impacting systemic T cell activation and radiosensitivity. Microbial metabolites, particularly short-chain fatty acids (SCFAs), mediate the conversion of regulatory T cells into tumoricidal CD8+ T lymphocytes, amplifying intratumoral immune cell infiltration following radiation treatment (, ). Inosine, a purine nucleoside produced by Bifidobacterium pseudolongum, enhances T cell-mediated killing via activation of A2A receptors, particularly under conditions of low glucose availability within the tumor microenvironment, thereby synergizing with radiotherapy. Clinical observations demonstrate significant associations between microbial community richness and abscopal response rates, with specific metabolites such as indole-3-propionic acid augmenting CD8+ T cell cytotoxicity through aryl hydrocarbon receptor (AhR)-dependent pathways ().
3.4 Engineering gut microbes for radiation benefits
The intestinal microbiota critically shapes radiation therapy outcomes by reprogramming metabolic networks and fine-tuning immune responses. Targeted interventions like probiotics, prebiotics, and fecal microbiota transplantation restore microbial balance, thereby augmenting tumor control while mitigating adverse effects (). At the molecular level, fasting-induced adipose factor (FIAF), an epithelial protein regulated by microbes, activates PPARγ signaling to enhance DNA repair in the intestinal epithelium, with radioprotective effects observed in microbiota-depleted animal models (). Specific microbial populations demonstrate distinct protective capacities: short-chain fatty acid-producing species (Enterococcus faecalis, Clostridium perfringens) attenuate radiation-induced oxidative damage through FIAF induction, whereas Bacteroides and Escherichia coli facilitate epithelial renewal via PPARγ-mediated mitochondrial proliferation (, ). Clinically, probiotic supplementation with Streptococcus, Lactobacillus, and Bifidobacterium augments FIAF expression through histone acetylation, synergizing with radiation to promote malignant cell apoptosis while reducing gastrointestinal toxicity (, ). The antibiotic vancomycin, with selective activity against Gram-positive bacteria, reshapes host–microbiome–immune dynamics to potentiate radiation-mediated tumor control. In B16-OVA melanoma and TC-1 carcinoma models, vancomycin reduces Clostridiales abundance, enhances MHC class I expression on dendritic cells, and augments IFN-γ-driven tumor clearance while modulating PD-L1 and CTLA-4 checkpoint pathways (). Antibiotic-induced dysbiosis further activates TLR2–MyD88 signaling, reprogramming Tregs into Th1 cells within gut-associated lymphoid tissues, which enhances antigen-presenting cell migration to tumor-draining lymph nodes and establishes durable systemic immunity (, ). Microbiota also influence local Treg dynamics during radiotherapy: Bacteroides-derived tryptophan catabolites stabilize Tregs via AhR activation, whereas microbial disruption impairs radiation-induced immunogenic cell death () (Figure 1).
Figure 1
4 Gut microbiota in chemotherapy responses
4.1 Intestinal microbiota in platinum drug efficacy
Platinum-derived chemotherapeutics exert cytotoxicity by inducing DNA crosslinks, mitochondrial dysfunction, and oxidative injury, with reactive oxygen species (ROS) as central mediators. Emerging evidence reveals that the gut microbiota potentiates platinum efficacy through ROS regulation. Lactobacillus acidophilus enhances oxaliplatin-induced DNA lesions by activating macrophage NADPH oxidase while impairing non-homologous end joining repair (). Conversely, antibiotic-driven microbial depletion attenuates oxidative stress and weakens drug response (). Additionally, Lactobacillus promotes CD8+ T cell infiltration into tumors via TLR2–MyD88 signaling, synergizing with cisplatin to strengthen cytotoxicity and remodel immunoregulatory niches, thereby extending survival in murine lung cancer models (). Clinically, antibiotic-associated microbial diversity loss correlates with diminished cisplatin efficacy, whereas probiotic supplementation with L. acidophilus restores responsiveness by reactivating TNF-α/IL-6–mediated inflammatory cascades. This recovery involves microbial short-chain fatty acids, notably butyrate, which epigenetically upregulate apoptotic genes (BAX, CASP3) through chromatin remodeling (, ).
4.2 Microbiota-driven modulation of cyclophosphamide efficacy
The alkylating agent cyclophosphamide (CTX) mediates antitumor efficacy through immunogenic cell death pathways that critically depend on microbial modulation of host immunity. CTX induces marked remodeling of the intestinal microbiota, characterized by reduced Bacteroidetes and enrichment of Firmicutes, including Bacteroides acidifaciens and Alistipes, which correlate with improved therapeutic response (). CTX promotes translocation of Gram-positive bacterial components (Lactobacillus spp.) into secondary lymphoid tissues, where TLR4-dependent dendritic cell activation drives Th17 polarization and strengthens memory Th1 responses, leading to increased intratumoral IFN-γ–producing cytotoxic T cells (). In axenic or vancomycin-treated mice, this immune axis is disrupted, while microbial reconstitution restores CTX efficacy, underscoring the indispensable role of commensals in therapy responsiveness (). Additionally, CTX-driven microbial shifts suppress indoleamine 2,3-dioxygenase (IDO) activity, lowering kynurenine levels and diminishing Treg-mediated immunosuppression (, ), revealing potential microbial targets for enhancing chemotherapy response. The efficacy of gemcitabine, a nucleoside analog, is undermined not only by tumor-intrinsic resistance but also by microbial enzymatic degradation. Gammaproteobacteria, including Escherichia coli and Pseudomonas aeruginosa, secrete cytidine deaminase (CDD), which converts gemcitabine into its inactive metabolite 2′, 2′-difluorodeoxyuridine, a phenomenon especially prominent in pancreatic tumor microenvironments (). Crucially, the bacterial CDD long isoform drives this inactivation: coculture experiments show that Mycoplasma hyorhinis strains expressing CDD confer complete resistance even at gemcitabine levels tenfold higher than therapeutic doses. In contrast, targeted depletion of intratumoral bacteria or pharmacological inhibition of CDD restores chemosensitivity (). The identification of these mechanisms supports the development of microbiome-informed precision approaches to overcome chemoresistance.
4.3 Microbiome in irinotecan-induced gastrointestinal toxicity
The gastrointestinal toxicity of irinotecan arises from enterohepatic cycling and microbial enzymatic reactivation. After hepatic carboxylesterase-mediated conversion to the active metabolite SN-38, subsequent glucuronidation produces the inactive conjugate SN-38-G, which is secreted into the intestinal lumen (). Commensal bacteria, particularly Enterobacteriaceae and Clostridium species, expressing β-glucuronidase, hydrolyze SN-38-G back to its active form, thereby disrupting epithelial integrity and provoking severe diarrhea (). At the molecular level, β-glucuronidase-producing strains, exemplified by Escherichia coli K-12, amplify intestinal inflammation via TLR4–MAPK signaling, with their abundance correlating with clinical diarrhea severity. Interventions that inhibit β-glucuronidase or reshape microbial communities through probiotics (Lactobacillus) significantly reduce luminal SN-38 levels, alleviating chemotherapy-induced diarrhea (). Microbiome profiling reveals that the relative abundance of Firmicutes versus Bacteroidetes, along with overall microbial diversity, serves as predictive biomarkers for irinotecan-related enterotoxicity risk. Patients exhibiting diminished microbial richness show increased susceptibility to severe gastrointestinal complications, highlighting the potential of microbiota characterization for optimizing individualized treatment protocols to minimize adverse effects (Supplementary Table S1).
4.4 TLR9 agonists and microbiota in antitumor response
The immunostimulatory potential of TLR9 is mediated by recognition of bacterial CpG motifs, whereby synthetic CpG oligodeoxynucleotides (CpG-ODNs) engage TLR9 on antigen-presenting cells, triggering tumor necrosis factor (TNF) release, immunogenic apoptosis, and hemorrhagic tumor destruction (). Antibiotic-induced depletion of Gram-negative bacteria reduces LPS availability, suppressing TNF, IL-1α, and IL-12β production by tumor-infiltrating myeloid cells and abolishing CpG-ODN efficacy in colorectal carcinoma. Restoration of TLR4 signaling through exogenous LPS reactivates MyD88/TRIF-dependent cascades, reversing antibiotic-mediated immunosuppression and confirming microbial regulation of antitumor responses via TLR4 pathways (). At the molecular level, the gut commensal Alistipes shahii potentiates CpG-ODN activity through sphingolipid-mediated NLRP3 inflammasome activation in dendritic cells, driving IL-1β-mediated lymphocyte recruitment and tumor microenvironment modification (, ). Together, these findings underscore microbial–TLR crosstalk as a critical determinant of immunotherapeutic success, supporting microbiome-informed strategies that integrate TLR agonists with targeted microbial modulation.
5 Microbiome regulation of immune checkpoint inhibitor efficacy
The therapeutic activity of immune checkpoint inhibitors (ICIs) targeting CTLA-4 and PD-1/PD-L1 pathways is fundamentally regulated by intestinal microbiome-mediated immune modulation (–). CTLA-4 blockade induces Treg depletion while promoting cytotoxic T lymphocyte (CTL) accumulation, whereas PD-L1 inhibition reverses T cell dysfunction by downregulating inhibitory receptors (TIM-3, LAG-3) (). Specific bacterial species demonstrate immunostimulatory effects: Bacteroides thetaiotaomicron and B. fragilis potentiate CTLA-4 inhibitor responses through dendritic cell activation via TLR4/MyD88-dependent mechanisms, elevating IL-12 production and Th1 polarization (). Likewise, Bifidobacterium species potentiate PD-L1 blockade by modulating indole-3-propionic acid metabolism, thereby improving mitochondrial oxidative fitness in CD8+ T cells (). Clinically, antibiotic-induced disruption of B. fragilis impairs CTLA-4 inhibitor responses, an effect reversible by bacterial reconstitution (). Besides, microbial community diversity influences tumor progression kinetics, with FMT or Bifidobacterium supplementation restoring dendritic cell cross-priming and CD8+ infiltration, yielding antitumor effects comparable to PD-L1 blockade and complete responses in combination. These findings delineate a sophisticated microbiome-immune-metabolism network that critically determines ICI responsiveness, offering new avenues for microbial-based therapeutic interventions.
6 Microbiota-mediated protection in chemotherapy and radiotherapy
Beneficial microorganisms exert therapeutic effects against chemotherapy-induced intestinal injury by reprogramming host–microbiome interactions, primarily through suppression of ROS and modulation of pattern recognition receptor pathways (, ). Probiotic consortia containing Lactobacillus acidophilus and Bifidobacterium spp. reduce cisplatin-associated mucosal inflammation and preserve epithelial barrier integrity in preclinical colorectal cancer models via inhibition of NADPH oxidase–driven oxidative stress (). The pathophysiology of methotrexate-related intestinal damage involves TLR4-MyD88/TRIF signaling activation, whereby cytotoxic agents induce Gram-negative bacterial cell wall disintegration and subsequent LPS liberation, initiating pro-inflammatory TLR4-mediated responses. Probiotic administration counteracts this process through competitive exclusion of pathogenic organisms, consequently limiting LPS-mediated enterocyte programmed cell death and junctional protein breakdown (). Notably, certain isolates such as Lactobacillus rhamnosus GG secrete extracellular polysaccharides that regulate NLRP6 inflammasome function (), establishing a protective microbiota–gut–liver axis and offering innovative avenues for mitigating chemotherapy-related complications.
Radiotherapy-induced cytotoxicity in intestinal crypt cells disrupts mucosal integrity, driving microbial imbalance (Bacteroidetes/Firmicutes ratio) and increased gut permeability, which underlie sequelae such as radiation enteritis and oral mucositis (, ). Probiotic administration with Lactobacillus acidophilus, Bifidobacterium, and Lactobacillus casei mitigates oxidative stress via Nrf2–ARE activation, significantly reducing severe (grade ≥3) enteritis while preserving barrier integrity through maintenance of tight junction complexes (). At the molecular level, these commensals modulate host immunity by engaging TLR2/NF-κB signaling with microbial-derived SCFAs, thereby suppressing radiation-induced cytokine cascades (IL-6, TNF-α). Clinical studies in head and neck cancer further demonstrate that Lactobacillus-based interventions reduce radiation-associated oral mucositis by 42.7%, mediated through enhanced salivary EGF secretion and upregulated MUC2 glycoprotein synthesis, ultimately improving adherence to therapy (). Collectively, these findings define the microbiota–immune interface as a critical determinant of radiotherapy tolerance and provide a translational rationale for microbiota-targeted strategies in mitigating treatment-related complications.
7 Conclusion
Accumulating evidence identifies the gut microbiota as a key regulator of chemoradiotherapy efficacy through modulation of immune activation, epithelial repair, and DNA damage responses. Commensal species such as Bifidobacterium and Lactobacillus enhance antitumor immunity by increasing CD8+ T cell infiltration and promoting the effectiveness of immune checkpoint blockade. In parallel, microbial metabolites including SCFAs, bile acids, inosine, and polyamines influence histone acetylation, redox balance, and cytotoxic T cell function, offering new avenues for therapeutic enhancement. Microbial enzymatic activity can also shape drug metabolism and resistance, exemplified by gemcitabine inactivation via bacterial cytidine deaminase.
Nevertheless, substantial barriers hinder clinical translation. Interindividual variability in microbial composition driven by genetics, diet, and environment poses a challenge for standardizing interventions such as probiotics or fecal microbiota transplantation. Safety concerns must also be considered, including the risk of bacteremia, off-target immune modulation, and unintended dysbiosis in vulnerable patients. Moreover, a lack of validated microbial biomarkers and prospective clinical trials limits the predictive utility of microbiome-based strategies. Future research should focus on personalized microbial profiling, rational microbial consortia design, and rigorous mechanistic validation to enable safe and effective microbiota-informed oncology care.
Statements
Author contributions
LZ: Writing – original draft. BL: Writing – original draft. JR: Writing – original draft. SW: Writing – original draft, Writing – review & editing. JW: Writing – original draft, Writing – review & editing.
Funding
The author(s) declare that no financial support was received for the research and/or publication of this article.
Conflict of interest
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.
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Supplementary material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fonc.2025.1659467/full#supplementary-material
References
1
TengHWangYSuiXFanJLiSLeiXet al. Gut microbiota-mediated nucleotide synthesis attenuates the response to neoadjuvant chemoradiotherapy in rectal cancer. Cancer Cell. (2023) 41:124–138.e126. doi: 10.1016/j.ccell.2022.11.013
2
RoeselRStratiFBassoCEpistolioSSpinaPDjordjevicJet al. Combined tumor-associated microbiome and immune gene expression profiling predict response to neoadjuvant chemo-radiotherapy in locally advanced rectal cancer. Oncoimmunology. (2025) 14:2465015. doi:Â 10.1080/2162402X.2025.2465015
3
VendrellJACabello-AguilarSSenalRHeckendornEHenrySGodreuilSet al. Dysbiosis in human urinary microbiota may differentiate patients with a bladder cancer. Int J Mol Sci. (2024) 25:10159. doi:Â 10.3390/ijms251810159
4
GilesEDCookKLJenschkeRMCorletoKALandrockDMahmoodTNet al. Metabolic and transcriptional effects of bazedoxifene/conjugated estrogens in a model of obesity-associated breast cancer risk. JCI Insight. (2025) 10:e182694. doi:Â 10.1172/jci.insight.182694
5
MaerzJKSteimleALangeABenderAFehrenbacherBFrickJS. Outer membrane vesicles blebbing contributes to B. vulgatus mpk-mediated immune response silencing. Gut Microbes. (2018) 9:1–12. doi: 10.1080/19490976.2017.1344810
6
ChengCYChenYHThuy Tien VoTChui HongYWangCSCanh VoQet al. CORM-2 prevents human gingival fibroblasts from lipoteichoic acid-induced VCAM-1 and ICAM-1 expression by inhibiting TLR2/MyD88/TRAF6/PI3K/Akt/ROS/NF-κB signaling pathway. Biochem Pharmacol. (2022) 201:115099. doi: 10.1016/j.bcp.2022.115099
7
ZhengJAhmadAAYangYLiangZShenWFengMet al. Lactobacillus rhamnosus CY12 enhances intestinal barrier function by regulating tight junction protein expression, oxidative stress, and inflammation response in lipopolysaccharide-induced caco-2 cells. Int J Mol Sci. (2022) 23:11162. doi:Â 10.3390/ijms231911162
8
KimMQieYParkJKimCH. Gut microbial metabolites fuel host antibody responses. Cell Host Microbe. (2016) 20:202–14. doi: 10.1016/j.chom.2016.07.001
9
HouHChenDZhangKZhangWLiuTWangSet al. Gut microbiota-derived short-chain fatty acids and colorectal cancer: Ready for clinical translation? Current Pharmaceutical Analysis. (2022) 526:225–35. doi: 10.1016/j.canlet.2021.11.027
10
ZhangSZhaoTWangYMiJLiuJFanXet al. Intestinal microbiota regulates colonic inflammation in fluorosis mice by TLR/NF-κB pathway through short-chain fatty acids. Food Chem Toxicol. (2023) 178:113866. doi: 10.1016/j.fct.2023.113866
11
LiaoKWenJLiuZZhangBZhangXFuYet al. The role of intratumoral microbiome in the occurrence, proliferation, metastasis of colorectal cancer and its underlying therapeutic strategies. Ageing Res Rev. (2025) 111:102820. doi:Â 10.1016/j.arr.2025.102820
12
Stefanowicz-HajdukJGraczykPHeringAGucwaMNowakAHałasaR. An in vitro study on the cytotoxic, antioxidant, and antimicrobial properties of yamogenin-A plant steroidal saponin and evaluation of its mechanism of action in gastric cancer cells. Int J Mol Sci. (2024) 25:4627. doi: 10.3390/ijms25094627
13
NanKZhongZYueYShenYZhangHWangZet al. Fasting-mimicking diet-enriched Bifidobacterium pseudolongum suppresses colorectal cancer by inducing memory CD8(+) T cells. Gut. (2025) 74:775–86. doi: 10.1136/gutjnl-2024-333020
14
Vargas-CastellanosERincón-RiverosA. Microsatellite instability in the tumor microenvironment: the role of inflammation and the microbiome. Cancer Med. (2025) 14:e70603. doi: 10.1002/cam4.70603
15
XiaoHWCuiMLiYDongJLZhangSQZhuCCet al. Gut microbiota-derived indole 3-propionic acid protects against radiation toxicity via retaining acyl-CoA-binding protein. Microbiome. (2020) 8:69. doi:Â 10.1186/s40168-020-00845-6
16
MedeirosMCTheSBellileERussoNSchmitdLDanellaEet al. : Salivary microbiome changes distinguish response to chemoradiotherapy in patients with oral cancer. Microbiome. (2023) 11:268. doi:Â 10.1186/s40168-023-01677-w
17
ZhangHFuLLeiliangXQuCWuWWenRet al. Beyond the Gut: The intratumoral microbiome’s influence on tumorigenesis and treatment response. Cancer Commun (Lond). (2024) 44:1130–67. doi: 10.1002/cac2.12597
18
RossiniARumioCSfondriniLTagliabueEMorelliDMiceliRet al. Influence of antibiotic treatment on breast carcinoma development in proto-neu transgenic mice. Cancer Res. (2006) 66:6219–24. doi: 10.1158/0008-5472.CAN-05-4592
19
YangZMaJHanJLiALiuGSunYet al. Gut microbiome model predicts response to neoadjuvant immunotherapy plus chemoradiotherapy in rectal cancer. Med. (2024) 5:1293–1306.e1294. doi: 10.1016/j.medj.2024.07.002
20
PanBYaoYWuHYeDZhangZZhangXet al. N-glycosylated LTβR increases the Th17/Treg cell ratio in liver cancer by blocking RORC ubiquitination and FOXP3 transcription. Cell Death Dis. (2025) 16:421. doi: 10.1038/s41419-025-07738-2
21
JinYPanZZhouJWangKZhuPWangYet al. Hedgehog signaling pathway regulates Th17 cell differentiation in asthma via IL-6/STAT3 signaling. Int Immunopharmacol. (2024) 139:112771. doi:Â 10.1016/j.intimp.2024.112771
22
MowatCDhattJBhattiIHamieABakerK. Short chain fatty acids prime colorectal cancer cells to activate antitumor immunity. Front Immunol. (2023) 14:1190810. doi:Â 10.3389/fimmu.2023.1190810
23
MengDKongWChengSLiuHHuangC. Gut-brain-liver axis in growth hormone deficiency: role of microbiota-derived short-chain fatty acids in ethnic variability and therapeutic development. Front Public Health. (2025) 13:1541654. doi:Â 10.3389/fpubh.2025.1541654
24
LouFYanLLuoSDongYXuJKangNet al. Dysbiotic oral microbiota-derived kynurenine, induced by chronic restraint stress, promotes head and neck squamous cell carcinoma by enhancing CD8(+) T cell exhaustion. Gut. (2025) 74:935–47. doi: 10.1136/gutjnl-2024-333479
25
JovelJNimagaAJordanTO’KeefeSPattersonJThiesenAet al. Metagenomics versus metatranscriptomics of the murine gut microbiome for assessing microbial metabolism during inflammation. Front Microbiol. (2022) 13:829378. doi: 10.3389/fmicb.2022.829378
26
GaoYZhangQSunJLiangYZhangMZhaoMet al. Extracellular vesicles derived from PM2.5-exposed alveolar epithelial cells mediate endothelial adhesion and atherosclerosis in ApoE(-/-) mice. FASEB J. (2022) 36:e22161. doi:Â 10.1096/fj.202100927RR
27
KearnsR. Gut modulation to regulate NF-κB in colorectal and gastric cancer therapy and inflammation. Cancer Immunol Immunother. (2025) 74:264. doi: 10.1007/s00262-025-04118-9
28
BaruahNAhamadNHalderPKoleyHKattiDS. Facile synthesis of multi-faceted, biomimetic and cross-protective nanoparticle-based vaccines for drug-resistant Shigella: a flexible platform technology. J Nanobiotechnology. (2023) 21:34. doi:Â 10.1186/s12951-023-01780-y
29
LiuYMaPLiuDLiuYRanZYangLet al. Gram-negative intratumoral bacteria mediate lymph node metastasis through LPS-TLR4/MAPK signaling pathway in cervical cancer. J Infect. (2025) 91:106532. doi:Â 10.1016/j.jinf.2025.106532
30
ZhangHHeZChenYChaoJChengXMaoJet al. Cordyceps polysaccharide improves polycystic ovary syndrome by inhibiting gut-derived LPS/TLR4 pathway to attenuates insulin resistance. Int J Biol Macromol. (2024) 280:135844. doi:Â 10.1016/j.ijbiomac.2024.135844
31
QinZWangRHouPZhangYYuanQWangYet al. TCR signaling induces STAT3 phosphorylation to promote TH17 cell differentiation. J Exp Med. (2024) 221:e20230683. doi:Â 10.1084/jem.20230683
32
KayamaHTakedaK. Polysaccharide A of Bacteroides fragilis: actions on dendritic cells and T cells. Mol Cell. (2014) 54:206–7. doi: 10.1016/j.molcel.2014.04.002
33
YuanMJiangZBiGNomuraKLiuMWangYet al. Pattern-recognition receptors are required for NLR-mediated plant immunity. Nature. (2021) 592:105–9. doi: 10.1038/s41586-021-03316-6
34
PeukerKMuffSWangJKünzelSBosseEZeissigYet al. Epithelial calcineurin controls microbiota-dependent intestinal tumor development. Nat Med. (2016) 22:506–15. doi: 10.1038/nm.4072
35
YangYWengWPengJHongLYangLToiyamaYet al. Fusobacterium nucleatum increases proliferation of colorectal cancer cells and tumor development in mice by activating toll-like receptor 4 signaling to nuclear factor-κB, and up-regulating expression of microRNA-21. Gastroenterology. (2017) 152:851–866.e824. doi: 10.1053/j.gastro.2016.11.018
36
AlvaradoAGThiagarajanPSMulkearns-HubertEESilverDJHaleJSAlbanTJet al. Glioblastoma cancer stem cells evade innate immune suppression of self-renewal through reduced TLR4 expression. Cell Stem Cell. (2017) 20:450–461.e454. doi: 10.1016/j.stem.2016.12.001
37
MaoQJiangFYinRWangJXiaWDongGet al. Interplay between the lung microbiome and lung cancer. Cancer Lett. (2018) 415:40–8. doi: 10.1016/j.canlet.2017.11.036
38
WangZZhaoYZhangLJCPA. Emerging trends and hot topics in the application of multi-omics in drug discovery: A bibliometric and visualized study. Curr Pharm Anal. (2024) 21:20–32. doi: 10.1016/j.cpan.2024.12.001
39
ParkJHSeoYHJangJHJeongCHLeeSParkB. Asiatic acid attenuates methamphetamine-induced neuroinflammation and neurotoxicity through blocking of NF-kB/STAT3/ERK and mitochondria-mediated apoptosis pathway. J Neuroinflamm. (2017) 14:240. doi:Â 10.1186/s12974-017-1009-0
40
YangYMaLXuYLiuYLiWCaiJet al. Enalapril overcomes chemoresistance and potentiates antitumor efficacy of 5-FU in colorectal cancer by suppressing proliferation, angiogenesis, and NF-κB/STAT3-regulated proteins. Cell Death Dis. (2020) 11:477. doi: 10.1038/s41419-020-2675-x
41
RuanZLiangMShangLLaiMDengXSuX. Shikonin-mediated PD-L1 degradation suppresses immune evasion in pancreatic cancer by inhibiting NF-κB/STAT3 and NF-κB/CSN5 signaling pathways. Pancreatology. (2021) 21:630–41. doi: 10.1016/j.pan.2021.01.023
42
SaeedAEshratFFUmarSSaeedA. The duplex interaction of microbiome with chemoradiation and immunotherapy: potential implications for colorectal cancer. Curr Colorectal Cancer Rep. (2019) 15:98–104. doi: 10.1007/s11888-019-00435-1
43
FrankMHennenbergEMEykingARünziMGerkenGScottPet al. TLR signaling modulates side effects of anticancer therapy in the small intestine. J Immunol. (2015) 194:1983–95. doi: 10.4049/jimmunol.1402481
44
ManichanhCVarelaEMartinezCAntolinMLlopisMDoréJet al. The gut microbiota predispose to the pathophysiology of acute postradiotherapy diarrhea. Am J Gastroenterol. (2008) 103:1754–61. doi: 10.1111/j.1572-0241.2008.01868.x
45
MitraAGrossman BiegertGWDelgadoAYKarpinetsTVSolleyTNMezzariMPet al. Microbial diversity and composition is associated with patient-reported toxicity during chemoradiation therapy for cervical cancer. Int J Radiat Oncol Biol Phys. (2020) 107:163–71. doi: 10.1016/j.ijrobp.2019.12.040
46
NamYDKimHJSeoJGKangSWBaeJW. Impact of pelvic radiotherapy on gut microbiota of gynecological cancer patients revealed by massive pyrosequencing. PloS One. (2013) 8:e82659. doi:Â 10.1371/journal.pone.0082659
47
WangALingZYangZKielaPRWangTWangCet al. Gut microbial dysbiosis may predict diarrhea and fatigue in patients undergoing pelvic cancer radiotherapy: a pilot study. PloS One. (2015) 10:e0126312. doi:Â 10.1371/journal.pone.0126312
48
AlexanderJLWilsonIDTeareJMarchesiJRNicholsonJKKinrossJM. Gut microbiota modulation of chemotherapy efficacy and toxicity. Nat Rev Gastroenterol Hepatol. (2017) 14:356–65. doi: 10.1038/nrgastro.2017.20
49
IidaNDzutsevAStewartCASmithLBouladouxNWeingartenRAet al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science. (2013) 342:967–70. doi: 10.1126/science.1240527
50
SivanACorralesLHubertNWilliamsJBAquino-MichaelsKEarleyZMet al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. (2015) 350:1084–9. doi: 10.1126/science.aac4255
51
VétizouMPittJMDaillèreRLepagePWaldschmittNFlamentCet al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. (2015) 350:1079–84. doi: 10.1126/science.aad1329
52
ViaudSSaccheriFMignotGYamazakiTDaillèreRHannaniDet al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science. (2013) 342:971–6. doi: 10.1126/science.1240537
53
YiYLuWShenLWuYZhangZ. The gut microbiota as a booster for radiotherapy: novel insights into radio-protection and radiation injury. Exp Hematol Oncol. (2023) 12:48. doi:Â 10.1186/s40164-023-00410-5
54
CuiMXiaoHLiYZhouLZhaoSLuoDet al. Faecal microbiota transplantation protects against radiation-induced toxicity. EMBO Mol Med. (2017) 9:448–61. doi: 10.15252/emmm.201606932
55
XueLLiZXueJWangHWuTLiuRet al. Lactobacillus acidophilus LA85 ameliorates cyclophosphamide-induced immunosuppression by modulating Notch and TLR4/NF-κB signal pathways and remodeling the gut microbiota. Food Funct. (2022) 13:8107–18. doi: 10.1039/D1FO04331E
56
DongJWangBXiaoYLiuJWangQXiaoHet al. Roseburia intestinalis sensitizes colorectal cancer to radiotherapy through the butyrate/OR51E1/RALB axis. Cell Rep. (2024) 43:113846. doi:Â 10.1016/j.celrep.2024.113846
57
LamVMoulderJESalzmanNHDubinskyEAAndersenGLBakerJE. Intestinal microbiota as novel biomarkers of prior radiation exposure. Radiat Res. (2012) 177:573–83. doi: 10.1667/RR2691.1
58
Hauer-JensenMDenhamJWAndreyevHJ. Radiation enteropathy–pathogenesis, treatment and prevention. Nat Rev Gastroenterol Hepatol. (2014) 11:470–9. doi: 10.1038/nrgastro.2014.46
59
DengLLiangHBurnetteBBeckettMDargaTWeichselbaumRRet al. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest. (2014) 124:687–95. doi: 10.1172/JCI67313
60
ParkBYeeCLeeKM. The effect of radiation on the immune response to cancers. Int J Mol Sci. (2014) 15:927–43. doi: 10.3390/ijms15010927
61
MatsonVFesslerJBaoRChongsuwatTZhaYAlegreMLet al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. (2018) 359:104–8. doi: 10.1126/science.aao3290
62
HooperLVLittmanDRMacphersonAJ. Interactions between the microbiota and the immune system. Science. (2012) 336:1268–73. doi: 10.1126/science.1223490
63
Uribe-HerranzMRafailSBeghiSGil-de-GómezLVerginadisIBittingerKet al. Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response. J Clin Invest. (2020) 130:466–79. doi: 10.1172/JCI124332
64
Uribe-HerranzMBittingerKRafailSGuedanSPieriniSTanesCet al. Gut microbiota modulates adoptive cell therapy via CD8α dendritic cells and IL-12. JCI Insight. (2018) 3:e94952. doi: 10.1172/jci.insight.94952
65
LiuJLiuCYueJ. Radiotherapy and the gut microbiome: facts and fiction. Radiat Oncol. (2021) 16:9. doi:Â 10.1186/s13014-020-01735-9
66
GrootaertCVan de WieleTVan RoosbroeckIPossemiersSVercoutter-EdouartASVerstraeteWet al. Bacterial monocultures, propionate, butyrate and H2O2 modulate the expression, secretion and structure of the fasting-induced adipose factor in gut epithelial cell lines. Environ Microbiol. (2011) 13:1778–89. doi: 10.1111/j.1462-2920.2011.02482.x
67
SchmuthMHaqqCMCairnsWJHolderJCDorsamSChangSet al. Peroxisome proliferator-activated receptor (PPAR)-beta/delta stimulates differentiation and lipid accumulation in keratinocytes. J Invest Dermatol. (2004) 122:971–83. doi: 10.1111/j.0022-202X.2004.22412.x
68
ChoudhuriRSowersALChandramouliGVRGamsonJKrishnaMCMitchellJBet al. The antioxidant tempol transforms gut microbiome to resist obesity in female C3H mice fed a high fat diet. Free Radic Biol Med. (2022) 178:380–90. doi: 10.1016/j.freeradbiomed.2021.12.006
69
IqbalMYuQTangJXiangJ. Unraveling the gut microbiota’s role in obesity: key metabolites, microbial species, and therapeutic insights. J Bacteriol. (2025) 207:e0047924. doi: 10.1128/jb.00479-24
70
AmabebeERobertFOAgbalalahTOrubuESF. Microbial dysbiosis-induced obesity: role of gut microbiota in homoeostasis of energy metabolism. Br J Nutr. (2020) 123:1127–37. doi: 10.1017/S0007114520000380
71
AtarashiKTanoueTOshimaKSudaWNaganoYNishikawaHet al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature. (2013) 500:232–6. doi: 10.1038/nature12331
72
IsaacSScherJUDjukovicAJiménezNLittmanDRAbramsonSBet al. Short- and long-term effects of oral vancomycin on the human intestinal microbiota. J Antimicrob Chemother. (2017) 72:128–36. doi: 10.1093/jac/dkw383
73
MuroyamaYNirschlTRKochelCMLopez-BujandaZTheodrosDMaoWet al. Stereotactic radiotherapy increases functionally suppressive regulatory T cells in the tumor microenvironment. Cancer Immunol Res. (2017) 5:992–1004. doi: 10.1158/2326-6066.CIR-17-0040
74
ZitvogelLMaYRaoultDKroemerGGajewskiTF. The microbiome in cancer immunotherapy: Diagnostic tools and therapeutic strategies. Science. (2018) 359:1366–70. doi: 10.1126/science.aar6918
75
GuiQFLuHFZhangCXXuZRYangYH. Well-balanced commensal microbiota contributes to anti-cancer response in a lung cancer mouse model. Genet Mol Res. (2015) 14:5642–51. doi: 10.4238/2015.May.25.16
76
XuXZhangX. Effects of cyclophosphamide on immune system and gut microbiota in mice. Microbiol Res. (2015) 171:97–106. doi: 10.1016/j.micres.2014.11.002
77
Perez-ChanonaETrinchieriG. The role of microbiota in cancer therapy. Curr Opin Immunol. (2016) 39:75–81. doi: 10.1016/j.coi.2016.01.003
78
GellerLTBarzily-RokniMDaninoTJonasOHShentalNNejmanDet al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science. (2017) 357:1156–60. doi: 10.1126/science.aah5043
79
RoySTrinchieriG. Microbiota: a key orchestrator of cancer therapy. Nat Rev Cancer. (2017) 17:271–85. doi: 10.1038/nrc.2017.13
80
GuiducciCVicariAPSangalettiSTrinchieriGColomboMP. Redirecting in vivo elicited tumor infiltrating macrophages and dendritic cells towards tumor rejection. Cancer Res. (2005) 65:3437–46. doi: 10.1158/0008-5472.CAN-04-4262
81
XiangZLuJRaoSFuCYaoYYiYet al. Programming peptide-oligonucleotide nano-assembly for engineering of neoantigen vaccine with potent immunogenicity. Theranostics. (2024) 14:2290–303. doi: 10.7150/thno.93395
82
KimSKParkKYChoeJY. Toll-like receptor 9 is involved in NLRP3 inflammasome activation and IL-1β Production through monosodium urate-induced mitochondrial DNA. Inflammation. (2020) 43:2301–11. doi: 10.1007/s10753-020-01299-6
83
SensiBAngelicoRTotiLConteLCoppolaATisoneGet al. Mechanism, potential, and concerns of immunotherapy for hepatocellular carcinoma and liver transplantation. Curr Mol Pharmacol. (2024) 17:e18761429310703. doi:Â 10.2174/0118761429310703240823045808
84
LinAJiangAHuangLLiYZhangCZhuLet al. From chaos to order: optimizing fecal microbiota transplantation for enhanced immune checkpoint inhibitors efficacy. Gut Microbes. (2025) 17:2452277. doi:Â 10.1080/19490976.2025.2452277
85
WangYWangJLiuJZhuH. Immune-related diagnostic markers for benign prostatic hyperplasia and their potential as drug targets. Front Immunol. (2024) 15:1516362. doi:Â 10.3389/fimmu.2024.1516362
86
SharmaPAllisonJP. The future of immune checkpoint therapy. Science. (2015) 348:56–61. doi: 10.1126/science.aaa8172
87
GuoSXingSWuZChenFPanXLiQet al. Leucine restriction sameliorates Fusobacterium nucleatum-driven Malignant progression and radioresistance in nasopharyngeal carcinoma. Cell Rep Med. (2024) 5:101753. doi:Â 10.1016/j.xcrm.2024.101753
88
XueQLaiHZhangHLiGPiFWuQet al. Selenium attenuates radiation colitis by regulating cGAS-STING signaling. Adv Sci (Weinh). (2024) 11:e2403918. doi:Â 10.1002/advs.202403918
89
WangYLuoXPanHHuangWWangXWenHet al. Pharmacological inhibition of NADPH oxidase protects against cisplatin induced nephrotoxicity in mice by two step mechanism. Food Chem Toxicol. (2015) 83:251–60. doi: 10.1016/j.fct.2015.05.007
90
YuJZhuYHYangGYZhangWZhouDSuJHet al. Anti-inflammatory capacity of Lactobacillus rhamnosus GG in monophasic variant Salmonella infected piglets is correlated with impeding NLRP6-mediated host inflammatory responses. Vet Microbiol. (2017) 210:91–100. doi: 10.1016/j.vetmic.2017.08.008
91
ChenJLinALuoPJCPA. Advancing pharmaceutical research: A comprehensive review of cutting-edge tools and technologies. Curr Pharm Anal. (2024) 21:1–19. doi: 10.1016/j.cpan.2024.11.001
Summary
Keywords
gut microbiota, chemoradiotherapy, immune checkpoint inhibitors, probiotics, microbial metabolites, dysbiosis
Citation
Zhou L, Li B, Ren J, Wang S and Wang J (2025) Microbiome-mediated regulation of chemoradiotherapy response. Front. Oncol. 15:1659467. doi: 10.3389/fonc.2025.1659467
Received
04 July 2025
Accepted
16 September 2025
Published
01 October 2025
Volume
15 - 2025
Edited by
Wei Wang, Nanjing Medical University, China
Reviewed by
Lisa Jia Tran, Ludwig Maximilian University of Munich, Germany
Updates
Copyright
© 2025 Zhou, Li, Ren, Wang and Wang.
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.
*Correspondence: Jun Wang, 1196433508@qq.com; Shoujin Wang, 490562382@qq.com
†These authors have contributed equally to this work
Disclaimer
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