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从微生物稳态到全身发病机制:关于肠道菌群在神经精神、代谢和癌症疾病中作用的叙述性综述

From Microbial Homeostasis to Systemic Pathogenesis: A Narrative Review on Gut Flora's Role in Neuropsychiatric, Metabolic, and Cancer Disorders.

作者信息

Yan Xili, Shi Liangbin, Zhu Xiuling, Zhao Yingdi, Luo Jie, Li Qiang, Xu Zhiliang, Zhao Jian

机构信息

School of Graduate Medicine, Wannan Medical College, Wuhu, Anhui, 241002, People's Republic of China.

Department of Human Anatomy, School of Basic Medical Science, Wannan Medical College, Wuhu, Anhui, 241002, People's Republic of China.

出版信息

J Inflamm Res. 2025 Jul 5;18:8851-8873. doi: 10.2147/JIR.S531671. eCollection 2025.


DOI:10.2147/JIR.S531671
PMID:40635765
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12239926/
Abstract

As a pivotal ecological regulator in humans, the gut microbiota profoundly participates in the pathological processes of neurodegenerative diseases, psychiatric disorders, metabolic syndromes, and cancers through metabolite exchange, epigenetic regulation, and gut-brain axis signaling. This review focuses on analyzing relationships between gut microbial communities and four major disease spectra: neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease)-revealing microbiota-derived lipopolysaccharide activation of microglia and gut-brain transmission pathways of α-synuclein; mental health disorders (depression, schizophrenia, bipolar disorder)-elucidating dysregulated tryptophan metabolism and gut-derived neurotransmitter imbalances; metabolic diseases (obesity, diabetes, gout)-analyzing molecular mechanisms by which short-chain fatty acids regulate insulin sensitivity and uric acid metabolism; malignant tumors (lung cancer, breast cancer, prostate cancer)-exploring microbial remodeling of immune checkpoint inhibitor responses and regulatory effects on estrogen metabolism. We integrate existing evidence to systematically expound the roles of gut microbiota alterations in the pathogenesis of neurodegenerative diseases, psychiatric disorders, metabolic dysregulation, and malignant tumors, with in-depth analysis of mechanisms through which dysbiosis promotes disease progression, aiming to provide a theoretical foundation and scientific recommendations for developing microbiota-targeted precision intervention strategies (including, but not limited to synthetic microbial community transplantation and metabolite-directed regulation).

摘要

作为人体关键的生态调节因子,肠道微生物群通过代谢物交换、表观遗传调控和肠-脑轴信号传导,深度参与神经退行性疾病、精神疾病、代谢综合征和癌症的病理过程。本综述着重分析肠道微生物群落与四大主要疾病谱之间的关系:神经退行性疾病(阿尔茨海默病、帕金森病、亨廷顿病)——揭示微生物群衍生的脂多糖激活小胶质细胞以及α-突触核蛋白的肠-脑传播途径;精神健康障碍(抑郁症、精神分裂症、双相情感障碍)——阐明色氨酸代谢失调和肠道衍生神经递质失衡;代谢疾病(肥胖症、糖尿病、痛风)——分析短链脂肪酸调节胰岛素敏感性和尿酸代谢的分子机制;恶性肿瘤(肺癌、乳腺癌、前列腺癌)——探索微生物对免疫检查点抑制剂反应的重塑以及对雌激素代谢的调节作用。我们整合现有证据,系统阐述肠道微生物群改变在神经退行性疾病、精神疾病、代谢失调和恶性肿瘤发病机制中的作用,并深入分析生态失调促进疾病进展的机制,旨在为制定以微生物群为靶点的精准干预策略(包括但不限于合成微生物群落移植和代谢物导向调节)提供理论基础和科学建议。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84d9/12239926/f26854c94d0e/JIR-18-8851-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84d9/12239926/10a976fba051/JIR-18-8851-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84d9/12239926/5b128bcf31bc/JIR-18-8851-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84d9/12239926/a508be3c00ff/JIR-18-8851-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84d9/12239926/f26854c94d0e/JIR-18-8851-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84d9/12239926/10a976fba051/JIR-18-8851-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84d9/12239926/5b128bcf31bc/JIR-18-8851-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84d9/12239926/a508be3c00ff/JIR-18-8851-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84d9/12239926/f26854c94d0e/JIR-18-8851-g0004.jpg

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本文引用的文献

[1]
Decreased gut microbiome-derived indole-3-propionic acid mediates the exacerbation of myocardial ischemia/reperfusion injury following depression via the brain-gut-heart axis.

Redox Biol. 2025-4

[2]
Activation of Sirt6 by icariside Ⅱ alleviates depressive behaviors in mice with poststroke depression by modulating microbiota-gut-brain axis.

J Adv Res. 2025-3-2

[3]
Indole derivatives ameliorated the methamphetamine-induced depression and anxiety via aryl hydrocarbon receptor along "microbiota-brain" axis.

Gut Microbes. 2025-12

[4]
Excess Ub-K48 Induces Neuronal Apoptosis in Alzheimer's Disease.

J Integr Neurosci. 2024-12-24

[5]
Gut feeling: Exploring the intertwined trilateral nexus of gut microbiota, sex hormones, and mental health.

Front Neuroendocrinol. 2025-1

[6]
Intestinal Epithelial Serotonin as a Novel Target for Treating Disorders of Gut-Brain Interaction and Mood.

Gastroenterology. 2025-4

[7]
The involvement of the microbiota-gut-brain axis in the pathophysiology of mood disorders and therapeutic implications.

Expert Rev Neurother. 2025-1

[8]
Beyond digestion: Exploring how the gut microbiota modulates human social behaviors.

Neuroscience. 2025-1-26

[9]
Electroacupuncture improves learning and memory deficits in diabetic encephalopathy rats by regulating the Nrf2/HO-1 pathway.

Brain Res. 2025-1-15

[10]
Gut microbiota regulates stress responsivity via the circadian system.

Cell Metab. 2025-1-7

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