Hou ZW, Zhang P, Chen C. Gut microbiota-multi-organ axis and neuroinflammatory network: A potential integrative hub in aging and age-related diseases. World J Gastroenterol 2026; 32(36): 119520 [DOI: 10.3748/wjg.119520]
Corresponding Author of This Article
Chen Chen, PhD, Chief Physician, Department of Neurology, Affiliated Cardiovascular Hospital of Shanxi Medical University, No. 18 Yifen Street, Taiyuan 030024, Shanxi Province, China. chen.chen@sxmu.edu.cn
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Clinical Neurology
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Hou ZW, Zhang P, Chen C. Gut microbiota-multi-organ axis and neuroinflammatory network: A potential integrative hub in aging and age-related diseases. World J Gastroenterol 2026; 32(36): 119520 [DOI: 10.3748/wjg.119520]
World J Gastroenterol. Sep 28, 2026; 32(36): 119520 Published online Sep 28, 2026. doi: 10.3748/wjg.119520
Gut microbiota-multi-organ axis and neuroinflammatory network: A potential integrative hub in aging and age-related diseases
Zi-Wei Hou, Pan Zhang, Chen Chen
Zi-Wei Hou, Academy of Medical Sciences, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Pan Zhang, School of Public Health, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Chen Chen, Department of Neurology, Affiliated Cardiovascular Hospital of Shanxi Medical University, Taiyuan 030024, Shanxi Province, China
Chen Chen, Shanxi Key Laboratory of Heart Failure Precision Medicine, Shanxi Cardiovascular Hospital, Taiyuan 030024, Shanxi Province, China
Co-first authors: Zi-Wei Hou and Pan Zhang.
Author contributions: Hou ZW and Zhang P performed the research, they contributed equally to this article, they are the co-first authors of this manuscript; Chen C designed the study; and all authors have read and approved the final version of the manuscript.
AI contribution statement: We declare that AI tools (specifically DeepSeek) were used only as a writing assistant to optimize language expression and grammar during the drafting process. No AI tools were used to generate the scientific content, original ideas, theoretical framework, literature analysis, or authors’ perspectives.
Supported by the Shanxi Province Chinese Medicine Science and Technology Special Research Project, No. 2024ZYY2A023; and the Integration of Medicine, Engineering, and Basic Medical Sciences Special Project of Shanxi Provincial Health Commission, No. 2025YGYL026.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Chen Chen, PhD, Chief Physician, Department of Neurology, Affiliated Cardiovascular Hospital of Shanxi Medical University, No. 18 Yifen Street, Taiyuan 030024, Shanxi Province, China. chen.chen@sxmu.edu.cn
Received: January 30, 2026 Revised: April 19, 2026 Accepted: May 14, 2026 Published online: September 28, 2026 Processing time: 203 Days and 23.3 Hours
Abstract
Population aging has emerged as a major global public health challenge. Increasing evidence suggests that the gut microbiota may serve as an important interface linking environmental exposures, host metabolism, and systemic health, and may be associated with aging and age-related diseases. Through multi-organ axes, including the gut-liver axis and gut-brain axis, the gut microbiota has been implicated in metabolic reprogramming, immune regulation, and neuroinflammation. This article summarizes current evidence on how the gut microbiota may influence aging through these multi-organ axes. We discuss the gut-liver axis as a potential metabolic conduit, the gut-brain axis as a candidate neuroimmune communication pathway, and neuroinflammation as a possible integrative link between peripheral disturbances and central nervous system dysfunction. Emerging observations suggest that aging may be characterized by nonlinear microbiota trajectories and functional enrichment in lipid metabolism pathways. Furthermore, we discuss the therapeutic potential of targeting microbial metabolism and highlight the unique advantages of traditional Chinese medicine in modulating gut microbiota through multi-component and multi-target mechanisms - while acknowledging that much of this evidence remains preliminary. Finally, we outline a conceptual framework for precision anti-aging strategies integrating microbiome science, multi-organ axis networks, and environmental factors, with the understanding that this framework is hypothesis-generating rather than clinically definitive.
Core Tip: Recent studies have observed functional remodeling of gut microbiota during aging, particularly enhanced lipid metabolism pathways. This article discusses the gut-liver axis and gut-brain axis as potential bridges linking microbial alterations to host aging, with neuroinflammation potentially acting as an integrative hub. Targeting the “microbiota-multi-organ axis-neuroinflammation” network may provide potential directions for future research on healthy aging.
