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

IntroductionIn 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...

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Main Authors: Hao Qiu, Yuhang Wen, Yadan Luo, Shuya Lv, Jingrong Huang, Baoting Chen, Ruilin Lu, Lvqin He, Qian Yang, Jianhong Han, Xuefeng Yan, Manli He, Mingde Zhao, Xiaoxia Zou, Congwei Gu
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Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1606669/full
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author Hao Qiu
Hao Qiu
Yuhang Wen
Yuhang Wen
Yadan Luo
Yadan Luo
Shuya Lv
Shuya Lv
Jingrong Huang
Jingrong Huang
Baoting Chen
Baoting Chen
Ruilin Lu
Ruilin Lu
Lvqin He
Lvqin He
Qian Yang
Qian Yang
Jianhong Han
Jianhong Han
Xuefeng Yan
Xuefeng Yan
Manli He
Manli He
Mingde Zhao
Mingde Zhao
Xiaoxia Zou
Xiaoxia Zou
Congwei Gu
Congwei Gu
Congwei Gu
author_facet Hao Qiu
Hao Qiu
Yuhang Wen
Yuhang Wen
Yadan Luo
Yadan Luo
Shuya Lv
Shuya Lv
Jingrong Huang
Jingrong Huang
Baoting Chen
Baoting Chen
Ruilin Lu
Ruilin Lu
Lvqin He
Lvqin He
Qian Yang
Qian Yang
Jianhong Han
Jianhong Han
Xuefeng Yan
Xuefeng Yan
Manli He
Manli He
Mingde Zhao
Mingde Zhao
Xiaoxia Zou
Xiaoxia Zou
Congwei Gu
Congwei Gu
Congwei Gu
author_sort Hao Qiu
collection DOAJ
description IntroductionIn 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. However, it is unclear whether these changes influenced the disease process through serum metabolites.MethodsWe 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.ResultsThe 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 content, 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.DiscussionThese results suggest that serum metabolites are influenced by gut microbiota and their metabolites. The variations in serum metabolites provide valuable insights into the relationship between gut microbiota and their metabolites in the context of nonalcoholic fatty liver disease.
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spelling doaj-art-445fa04f8b6a4a7ebbeadbd76da6380a2025-08-20T03:12:38ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-07-011610.3389/fendo.2025.16066691606669Gut microbiota regulates serum metabolites in mice with nonalcoholic fatty liver disease via gut metabolites: mechanisms involving branched-chain amino acids and unsaturated fatty acidsHao Qiu0Hao Qiu1Yuhang Wen2Yuhang Wen3Yadan Luo4Yadan Luo5Shuya Lv6Shuya Lv7Jingrong Huang8Jingrong Huang9Baoting Chen10Baoting Chen11Ruilin Lu12Ruilin Lu13Lvqin He14Lvqin He15Qian Yang16Qian Yang17Jianhong Han18Jianhong Han19Xuefeng Yan20Xuefeng Yan21Manli He22Manli He23Mingde Zhao24Mingde Zhao25Xiaoxia Zou26Xiaoxia Zou27Congwei Gu28Congwei Gu29Congwei Gu30Laboratory Animal Center, Southwest Medical University, Luzhou, ChinaModel Animal and Human Disease Research of Luzhou Key Laboratory, Southwest Medical University, Luzhou, ChinaLaboratory Animal Center, Southwest Medical University, Luzhou, ChinaModel Animal and Human Disease Research of Luzhou Key Laboratory, Southwest Medical University, Luzhou, ChinaLaboratory Animal Center, Southwest Medical University, Luzhou, ChinaModel Animal and Human Disease Research of Luzhou Key Laboratory, Southwest Medical University, Luzhou, ChinaLaboratory Animal Center, Southwest Medical University, Luzhou, ChinaModel Animal and Human Disease Research of Luzhou Key Laboratory, Southwest Medical University, Luzhou, ChinaLaboratory Animal Center, Southwest Medical University, Luzhou, ChinaModel Animal and Human Disease Research of Luzhou Key Laboratory, Southwest Medical University, Luzhou, ChinaLaboratory Animal Center, Southwest Medical University, Luzhou, ChinaModel Animal and Human Disease Research of Luzhou Key Laboratory, Southwest Medical University, Luzhou, ChinaLaboratory Animal Center, Southwest Medical University, Luzhou, ChinaModel Animal and Human Disease Research of Luzhou Key Laboratory, Southwest Medical University, Luzhou, ChinaLaboratory Animal Center, Southwest Medical University, Luzhou, ChinaModel Animal and Human Disease Research of Luzhou Key Laboratory, Southwest Medical University, Luzhou, ChinaLaboratory Animal Center, Southwest Medical University, Luzhou, ChinaModel Animal and Human Disease Research of Luzhou Key Laboratory, Southwest Medical University, Luzhou, ChinaLaboratory Animal Center, Southwest Medical University, Luzhou, ChinaModel Animal and Human Disease Research of Luzhou Key Laboratory, Southwest Medical University, Luzhou, ChinaLaboratory Animal Center, Southwest Medical University, Luzhou, ChinaModel Animal and Human Disease Research of Luzhou Key Laboratory, Southwest Medical University, Luzhou, ChinaLaboratory Animal Center, Southwest Medical University, Luzhou, ChinaModel Animal and Human Disease Research of Luzhou Key Laboratory, Southwest Medical University, Luzhou, ChinaLaboratory Animal Center, Southwest Medical University, Luzhou, ChinaModel Animal and Human Disease Research of Luzhou Key Laboratory, Southwest Medical University, Luzhou, ChinaLaboratory Animal Center, Southwest Medical University, Luzhou, ChinaModel Animal and Human Disease Research of Luzhou Key Laboratory, Southwest Medical University, Luzhou, ChinaLaboratory Animal Center, Southwest Medical University, Luzhou, ChinaModel Animal and Human Disease Research of Luzhou Key Laboratory, Southwest Medical University, Luzhou, ChinaDepartment of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, ChinaIntroductionIn 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. However, it is unclear whether these changes influenced the disease process through serum metabolites.MethodsWe 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.ResultsThe 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 content, 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.DiscussionThese results suggest that serum metabolites are influenced by gut microbiota and their metabolites. The variations in serum metabolites provide valuable insights into the relationship between gut microbiota and their metabolites in the context of nonalcoholic fatty liver disease.https://www.frontiersin.org/articles/10.3389/fendo.2025.1606669/fullnonalcoholic fatty liver diseaseserum metabolitesgut microbiotagut metabolitesmetabonomicsMetOrigin
spellingShingle Hao Qiu
Hao Qiu
Yuhang Wen
Yuhang Wen
Yadan Luo
Yadan Luo
Shuya Lv
Shuya Lv
Jingrong Huang
Jingrong Huang
Baoting Chen
Baoting Chen
Ruilin Lu
Ruilin Lu
Lvqin He
Lvqin He
Qian Yang
Qian Yang
Jianhong Han
Jianhong Han
Xuefeng Yan
Xuefeng Yan
Manli He
Manli He
Mingde Zhao
Mingde Zhao
Xiaoxia Zou
Xiaoxia Zou
Congwei Gu
Congwei Gu
Congwei Gu
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
Frontiers in Endocrinology
nonalcoholic fatty liver disease
serum metabolites
gut microbiota
gut metabolites
metabonomics
MetOrigin
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic nonalcoholic fatty liver disease
serum metabolites
gut microbiota
gut metabolites
metabonomics
MetOrigin
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1606669/full
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