From Microbial Homeostasis to Systemic Pathogenesis: A Narrative Review on Gut Flora’s Role in Neuropsychiatric, Metabolic, and Cancer Disorders
Xili Yan, Liangbin Shi, Xiu-Ling Zhu, Yingdi Zhao, Jie Luo, Qiang Li, Zhiliang Xu, Jian Zhao
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).