REVIEW article
Front. Endocrinol.
Sec. Gut Endocrinology
The Brain–Bone–Gut Axis: A Microbial Bridge Underlying Multisystem Comorbidities
Provisionally accepted
- 1Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, shanghai, China
- 2Suzhou Hospital of Traditional Chinese Medicine, Suzhou, China
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Multi-axis interactions among the skeletal system, immune system, and gut microbiota(GM) have become a prominent focus of interdisciplinary research. The brain – bone – gut axis, proposed in recent years, provides an integrative physiological framework describing a bidirectional regulatory network linking the central nervous system, bone metabolism, and the GM via neural, endocrine, and immune pathways, thereby offering a unified perspective on multi-organ comorbidities. This article systematically examines the interconnections and synergistic effects across three core pathways within this framework: the brain–bone axis, the gut – bone axis, and the gut-brain axis. It further emphasizes immune – inflammatory processes as a central hub that connects gut dysbiosis with bone metabolic disturbances and alterations in brain function. On this basis, we propose an integrated approach that combines microecological interventions with nutritional and exercise management to improve gut homeostasis, preserve skeletal health, and support brain function, with the overarching aim of generating coordinated benefits across organ systems.
Keywords: Brain–bone–gut axis, Gut Microbiota, inflammatory bowel disease, Neuroimmune regulation, Neuroinflammati, on, Osteoporosis, short-chain fatty acids
Received: 27 Nov 2025; Accepted: 09 Feb 2026.
Copyright: © 2026 Xu, Ma, You and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jiong Wu
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.