Mechanisms of the effect of gut microbes on depression through the microbiota-gut-brain axis

Depression is a significant public health issue which exerts profound psychological and social impacts on both individuals and society. However, existing therapeutic strategies often exhibit limited efficacy. Accumulating evidence underscores the vital role of gut microbiota in the pathophysiology o...

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Main Authors: Xiangyan Zhou, Sixing Wang, Xiaohui Wang, Xinran Chen, Pei Zhou, Kai Ma, Peng Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Nutrition
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnut.2025.1634548/full
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author Xiangyan Zhou
Xiangyan Zhou
Sixing Wang
Sixing Wang
Xiaohui Wang
Xinran Chen
Pei Zhou
Kai Ma
Peng Zhang
author_facet Xiangyan Zhou
Xiangyan Zhou
Sixing Wang
Sixing Wang
Xiaohui Wang
Xinran Chen
Pei Zhou
Kai Ma
Peng Zhang
author_sort Xiangyan Zhou
collection DOAJ
description Depression is a significant public health issue which exerts profound psychological and social impacts on both individuals and society. However, existing therapeutic strategies often exhibit limited efficacy. Accumulating evidence underscores the vital role of gut microbiota in the pathophysiology of depression through the microbiota-gut-brain (MGB) axis. This involves multiple mechanisms, including short-chain fatty acid (SCFA) metabolism, communication via the vagal nerve, regulation of the hypothalamic-pituitary-adrenal (HPA) axis, and immune-inflammatory interactions. This review provides a comprehensive review of the mechanisms through which gut microbiota influences depression via the MGB axis. It synthesizes recent achievements in this field and evaluates the potential of microbiome-targeted therapies for depression treatment. Furthermore, it outlines future research directions to establish a theoretical framework for novel therapeutic approaches and to foster the development of this area.
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spelling doaj-art-376ea9b4b6b9458db7c09258ced20fe52025-08-20T03:39:32ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2025-08-011210.3389/fnut.2025.16345481634548Mechanisms of the effect of gut microbes on depression through the microbiota-gut-brain axisXiangyan Zhou0Xiangyan Zhou1Sixing Wang2Sixing Wang3Xiaohui Wang4Xinran Chen5Pei Zhou6Kai Ma7Peng Zhang8Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaFirst Clinical Department, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaSecond Clinical Department, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaThe Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaFirst Clinical Department, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepression is a significant public health issue which exerts profound psychological and social impacts on both individuals and society. However, existing therapeutic strategies often exhibit limited efficacy. Accumulating evidence underscores the vital role of gut microbiota in the pathophysiology of depression through the microbiota-gut-brain (MGB) axis. This involves multiple mechanisms, including short-chain fatty acid (SCFA) metabolism, communication via the vagal nerve, regulation of the hypothalamic-pituitary-adrenal (HPA) axis, and immune-inflammatory interactions. This review provides a comprehensive review of the mechanisms through which gut microbiota influences depression via the MGB axis. It synthesizes recent achievements in this field and evaluates the potential of microbiome-targeted therapies for depression treatment. Furthermore, it outlines future research directions to establish a theoretical framework for novel therapeutic approaches and to foster the development of this area.https://www.frontiersin.org/articles/10.3389/fnut.2025.1634548/fullgut microbiotaMGB axisdepressionmetabolismneurotransmittersneuroinflammation
spellingShingle Xiangyan Zhou
Xiangyan Zhou
Sixing Wang
Sixing Wang
Xiaohui Wang
Xinran Chen
Pei Zhou
Kai Ma
Peng Zhang
Mechanisms of the effect of gut microbes on depression through the microbiota-gut-brain axis
Frontiers in Nutrition
gut microbiota
MGB axis
depression
metabolism
neurotransmitters
neuroinflammation
title Mechanisms of the effect of gut microbes on depression through the microbiota-gut-brain axis
title_full Mechanisms of the effect of gut microbes on depression through the microbiota-gut-brain axis
title_fullStr Mechanisms of the effect of gut microbes on depression through the microbiota-gut-brain axis
title_full_unstemmed Mechanisms of the effect of gut microbes on depression through the microbiota-gut-brain axis
title_short Mechanisms of the effect of gut microbes on depression through the microbiota-gut-brain axis
title_sort mechanisms of the effect of gut microbes on depression through the microbiota gut brain axis
topic gut microbiota
MGB axis
depression
metabolism
neurotransmitters
neuroinflammation
url https://www.frontiersin.org/articles/10.3389/fnut.2025.1634548/full
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