The role of microbiota in nonalcoholic fatty liver disease: mechanism of action and treatment strategy

Non-alcoholic fatty liver disease (NAFLD) is now the most prevalent chronic liver disease worldwide, ranging from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma. It poses a significant public health challenge. Growing evidence indicates that the gut mic...

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Main Authors: Siwen Shen, Yao Liu, Nuoya Wang, Zhenhe Huang, Guifang Deng
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2025.1621583/full
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author Siwen Shen
Yao Liu
Nuoya Wang
Zhenhe Huang
Guifang Deng
author_facet Siwen Shen
Yao Liu
Nuoya Wang
Zhenhe Huang
Guifang Deng
author_sort Siwen Shen
collection DOAJ
description Non-alcoholic fatty liver disease (NAFLD) is now the most prevalent chronic liver disease worldwide, ranging from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma. It poses a significant public health challenge. Growing evidence indicates that the gut microbiota plays a key role in the development and progression of NAFLD. Advances in sequencing technologies, microbiome and metabolomics have helped identify characteristic microbial patterns and microbial-derived metabolites associated with NAFLD. The gut-liver axis has emerged as a central pathway linking intestinal microbes to liver function. Microbiota-derived metabolites, such as short-chain fatty acids, bile acids (BAs), and trimethylamine N-oxide (TMAO), have dual roles in hepatic lipid accumulation, inflammation, and insulin resistance, providing new insight into NAFLD pathogenesis. This review summarizes the mechanisms by which disruptions in the gut-liver axis contribute to NAFLD progression. It also outlines the therapeutic effects and mechanisms of current probiotics, with particular emphasis on next-generation probiotics like Akkermansia muciniphila and the potential benefits of its inactivated forms. Furthermore, we explore the role of prebiotics, plant-derived compounds, and synthetic agents in modulating gut microbiota and liver health. The review highlights key associations between specific bacterial species, microbial metabolites, and NAFLD, offering a theoretical basis for microbiota-targeted precision interventions and new therapeutic directions.
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spelling doaj-art-9457a2c3f86b4af9939eeccae228cb5d2025-08-20T02:48:01ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-07-011610.3389/fmicb.2025.16215831621583The role of microbiota in nonalcoholic fatty liver disease: mechanism of action and treatment strategySiwen Shen0Yao Liu1Nuoya Wang2Zhenhe Huang3Guifang Deng4Department of Clinical Nutrition, Shenzhen Nanshan People’s Hospital, Shenzhen, ChinaDepartment of Clinical Nutrition, Shenzhen Nanshan People’s Hospital, Shenzhen, ChinaDepartment of Clinical Nutrition, Shenzhen Nanshan People’s Hospital, Shenzhen, ChinaDepartment of Geriatric Medicine, Shenzhen Nanshan People’s Hospital, Shenzhen, ChinaDepartment of Clinical Nutrition, Shenzhen Nanshan People’s Hospital, Shenzhen, ChinaNon-alcoholic fatty liver disease (NAFLD) is now the most prevalent chronic liver disease worldwide, ranging from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma. It poses a significant public health challenge. Growing evidence indicates that the gut microbiota plays a key role in the development and progression of NAFLD. Advances in sequencing technologies, microbiome and metabolomics have helped identify characteristic microbial patterns and microbial-derived metabolites associated with NAFLD. The gut-liver axis has emerged as a central pathway linking intestinal microbes to liver function. Microbiota-derived metabolites, such as short-chain fatty acids, bile acids (BAs), and trimethylamine N-oxide (TMAO), have dual roles in hepatic lipid accumulation, inflammation, and insulin resistance, providing new insight into NAFLD pathogenesis. This review summarizes the mechanisms by which disruptions in the gut-liver axis contribute to NAFLD progression. It also outlines the therapeutic effects and mechanisms of current probiotics, with particular emphasis on next-generation probiotics like Akkermansia muciniphila and the potential benefits of its inactivated forms. Furthermore, we explore the role of prebiotics, plant-derived compounds, and synthetic agents in modulating gut microbiota and liver health. The review highlights key associations between specific bacterial species, microbial metabolites, and NAFLD, offering a theoretical basis for microbiota-targeted precision interventions and new therapeutic directions.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1621583/fullNAFLD (non-alcoholic fatty liver disease)metabolic associated fatty liver disease (MAFLD)prebiotics and probioticsgut-liver axisbile acid
spellingShingle Siwen Shen
Yao Liu
Nuoya Wang
Zhenhe Huang
Guifang Deng
The role of microbiota in nonalcoholic fatty liver disease: mechanism of action and treatment strategy
Frontiers in Microbiology
NAFLD (non-alcoholic fatty liver disease)
metabolic associated fatty liver disease (MAFLD)
prebiotics and probiotics
gut-liver axis
bile acid
title The role of microbiota in nonalcoholic fatty liver disease: mechanism of action and treatment strategy
title_full The role of microbiota in nonalcoholic fatty liver disease: mechanism of action and treatment strategy
title_fullStr The role of microbiota in nonalcoholic fatty liver disease: mechanism of action and treatment strategy
title_full_unstemmed The role of microbiota in nonalcoholic fatty liver disease: mechanism of action and treatment strategy
title_short The role of microbiota in nonalcoholic fatty liver disease: mechanism of action and treatment strategy
title_sort role of microbiota in nonalcoholic fatty liver disease mechanism of action and treatment strategy
topic NAFLD (non-alcoholic fatty liver disease)
metabolic associated fatty liver disease (MAFLD)
prebiotics and probiotics
gut-liver axis
bile acid
url https://www.frontiersin.org/articles/10.3389/fmicb.2025.1621583/full
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