ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Gut Endocrinology
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1606669
Gut Microbiota Regulates Serum Metabolites in Mice with Nonalcoholic Fatty Liver Disease via Gut Metabolites: Mechanisms Involving Branched-Chain Amino Acids and Unsaturated Fatty Acids
Provisionally accepted
Hao Qiu1,2
Yuhang Wen1,2
Yadan Luo1,2
Shuya Lv1,2
Huang Jingrong1,2Baoting Chen1,2
瑞林 鲁1,2Lvqin He1,2Qian Yang1,2Jianhong Han1,2Xuefeng Yan1,2Manli He1,2Mingde Zhao1,2*Xiaoxia Zou1,2*
Congwei Gu1,2,3*- 1Laboratory Animal Center, Southwest Medical University, Luzhou, China
- 2Model Animal and Human Disease Research of Luzhou Key Laboratory, Luzhou, Sichuan Province, China
- 3Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, Sichuan Province, China
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In recent years, nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease globally. Studies indicate that the gut-liver axis plays an important role in the occurrence and development of this disease. Our previous studies showed that the gut microbiota and gut metabolites in mice with NAFLD changed significantly, but it is unclear whether these changes influenced the disease process through serum metabolites. We conducted a non-targeted metabolome analysis on serum metabolites and systematically investigated the correlations between serum metabolites, gut microbiota, gut metabolites, and phenotypic index. Additionally, we traced the potential origins of serum metabolites and analyzed host-microbial interactions to elucidate the underlying mechanisms linking changes in serum metabolites with gut microbiota and gut metabolites. The findings suggest that the imbalance of gut pathogenic microbiota, specifically Blautia and Helicobacter, and beneficial microbiota such as Allobaculum, in mice with nonalcoholic fatty liver disease may be an important cause of gut metabolic disorders. This disorder results in a reduction of unsaturated fatty acid contend, particularly a decrease in Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA), and an accumulation of branched fatty acids in the serum.Consequently, there is a significant elevation in liver injury indices, potentially exacerbating the progression of nonalcoholic fatty liver disease and obesity in mice. These results suggest that serum metabolites are influenced by gut microbiota and their metabolites, and the variations in serum
Keywords: nonalcoholic fatty liver disease, Serum metabolites, Gut Microbiota, gut metabolites, Metabonomics, MetOrigin
Received: 06 Apr 2025; Accepted: 30 Jun 2025.
Copyright: © 2025 Qiu, Wen, Luo, Lv, Jingrong, Chen, 鲁, He, Yang, Han, Yan, He, Zhao, Zou and Gu. 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) or licensor 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:
Mingde Zhao, Laboratory Animal Center, Southwest Medical University, Luzhou, China
Xiaoxia Zou, Model Animal and Human Disease Research of Luzhou Key Laboratory, Luzhou, Sichuan Province, China
Congwei Gu, Laboratory Animal Center, Southwest Medical University, Luzhou, China
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