Gut microbiome dysbiosis as a convergent contributor of neurodegenerative disease: unifying mechanistic pathways and emerging precision microbiome-directed therapies

Neurodegenerative diseases (NDDs) are increasingly recognized as systemic disorders shaped by the microbiota-gut-brain axis. Within this framework, gut microbiome dysbiosis is better defined by reproducible modules of functional imbalance than by isolated taxonomic shifts. These aberrant microbial networks transmit peripheral signals to the central nervous system through three interconnected routes: immune-inflammatory activation, metabolic reprogramming, and aberrant vagal and humoral neural transmission. Because peripheral inputs may converge on shared downstream pathways within the brain, they can drive mitochondrial decompensation, oxidative stress, and pathological protein aggregation. This review integrates current evidence into a conceptual framework describing how host-microbiome interactions may contribute to neurodegeneration and then critically appraises microbiome-targeted interventions, including dietary modulation, next-generation probiotics, and fecal microbiota transplantation. Moving from correlation-based reasoning toward a causal, mechanism-driven account, we argue for patient stratification and outline a path toward precision microecological therapies against NDDs.

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Publication Details

Journal
Frontiers in Immunology
Published
2026-11-09
DOI
https://doi.org/10.3389/fimmu.2026.1969319
Primary Topic
Gut microbiota and health
Type
article
Field-Weighted Citation Impact
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article

Gut microbiome dysbiosis as a convergent contributor of neurodegenerative disease: unifying mechanistic pathways and emerging precision microbiome-directed therapies

Yangtian Chen, Zongxin Ling, Guangyong Cai, Xiaocui Xu et al.
Frontiers in Immunology
Gut microbiota and health
article

Gut microbiome dysbiosis as a convergent contributor of neurodegenerative disease: unifying mechanistic pathways and emerging precision microbiome-directed therapies

Yangtian Chen, Zongxin Ling, Guangyong Cai, Xiaocui Xu, Lingbin Wu, Pingping Hu, Yongtao Gao, Shengyu Huang, Yiwen Cheng, Xia Liu
article en

Abstract

Neurodegenerative diseases (NDDs) are increasingly recognized as systemic disorders shaped by the microbiota-gut-brain axis. Within this framework, gut microbiome dysbiosis is better defined by reproducible modules of functional imbalance than by isolated taxonomic shifts. These aberrant microbial networks transmit peripheral signals to the central nervous system through three interconnected routes: immune-inflammatory activation, metabolic reprogramming, and aberrant vagal and humoral neural transmission. Because peripheral inputs may converge on shared downstream pathways within the brain, they can drive mitochondrial decompensation, oxidative stress, and pathological protein aggregation. This review integrates current evidence into a conceptual framework describing how host-microbiome interactions may contribute to neurodegeneration and then critically appraises microbiome-targeted interventions, including dietary modulation, next-generation probiotics, and fecal microbiota transplantation. Moving from correlation-based reasoning toward a causal, mechanism-driven account, we argue for patient stratification and outline a path toward precision microecological therapies against NDDs.

Frontiers in ImmunologyVol. 17
Nantong University (CN), Affiliated Hospital of Nantong University (CN), Lishui City People's Hospital (CN), First Affiliated Hospital Zhejiang University (CN), State Key Laboratory of Diagnosis and Treatment of Infectious Diseases (CN), Zhejiang University (CN)
Gut microbiota and health
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