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Peer-reviewedCC BY 4.0Frontiers in Immunology

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

  • Yangtian Chen1
  • Yiwen Cheng2
  • Shengyu Huang2
  • Xia Liu3
  • Xiaocui Xu1
  • Pingping Hu1
  • Lingbin Wu4
  • Zongxin Ling2
  • Yongtao Gao1
  • Guangyong Cai5
5 affiliations
  1. 1Department of Anesthesiology, Affiliated Hospital of Nantong University, Medical School of Nantong University
  2. 2State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine
  3. 3Department of Intensive Care Unit, The First Affiliated Hospital, Zhejiang University School of Medicine
  4. 4Department of Laboratory Medicine, Lishui Second People’s Hospital
  5. 5Lishui Key Laboratory of Brain Health and Severe Brain Disorders, Department of Rehabilitation, Lishui Second People’s Hospital
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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.

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Cite

BibTeXRIS
BibTeX
@article{chen2026microbiome,
  title = {{Gut microbiome dysbiosis as a convergent contributor of neurodegenerative disease: unifying mechanistic pathways and emerging precision microbiome-directed therapies}},
  author = {Yangtian Chen and Yiwen Cheng and Shengyu Huang and Xia Liu and Xiaocui Xu and Pingping Hu and Lingbin Wu and Zongxin Ling and Yongtao Gao and Guangyong Cai},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = nov,
  doi = {10.3389/fimmu.2026.1969319},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1969319/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Gut microbiome dysbiosis as a convergent contributor of neurodegenerative disease: unifying mechanistic pathways and emerging precision microbiome-directed therapies
AU  - Yangtian Chen
AU  - Yiwen Cheng
AU  - Shengyu Huang
AU  - Xia Liu
AU  - Xiaocui Xu
AU  - Pingping Hu
AU  - Lingbin Wu
AU  - Zongxin Ling
AU  - Yongtao Gao
AU  - Guangyong Cai
PY  - 2026
DA  - 2026/11/09
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1969319
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1969319/full
AB  - 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.
SN  - 1664-3224
ER  -