Gut microbiota as master regulators: Mapping gut-organ axes that orchestrate systemic health

The gut hosts the body's largest microbial ecosystem. Humans provide a habitat and nutrients for these microorganisms, which in turn generate microbial communities and metabolites, thereby interfacing with the host through hormonal, immune, and metabolic pathways. Substantial evidence indicates that disruption in host-microbiota communication is associated with the development and progression of various diseases. As the organs of the human body do not exist or function in isolation, investigating the mechanisms underlying the gut-organ axis is essential for advancing the treatment of both intestinal and extra-intestinal disorders.

A review in TransMed applies a multi-tool bibliometric methodology to map global collaborative networks and the distribution of scientific contributions over 25 years of gut-organ axis research. It provides an analysis of subfield characteristics and translational potential to help shape future research directions.

The authors found that literature on the gut-germline, gut-bone, gut-skin, and gut-immune axes remain underdeveloped, characterized by few research groups, small cohort sizes, and a near-absence of interventional trials with hard organ-specific endpoints.

Meanwhile, current probiotic and fecal microbiota transplantation trials are constrained by small sample sizes, heterogeneous designs, and reliance on surrogate endpoints. The authors urged that the next phase must abandon the one-strain-fits-all paradigm in favor of interventions stratified by host factors such as renal function, diet, baseline microbiota composition, and immune status, evaluated against hard clinical outcomes, and focused on mechanism-defined strategies producing consortia.

“In sum, the field has accumulated sufficient foundational knowledge,” says corresponding author Daiyuan Tang. “The next decade should be dedicated to explaining associations through coordinated methodological rigor rather than continuing to catalogue them to progress from mapping the gut-organ axis landscape to engineering it for therapeutic benefit.”

Contact the author:

Daiyuan Tang, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China, tangdaiyuan@ustc.edu.cn

Funder:

This study was supported by the National Natural Science Foundation of China (Nos. 82604738 and 82601086), Anhui Postdoctoral Scientific Research Program Foundation (No. 2026C1364), Nature Science Foundation of Henan Province of China (No. 262300422271), China Postdoctoral Science Foundation (Nos. 2025M772035 and 2026M792481), Henan Provincial Medical Science and Technology Research Joint Venture Project (No. LHGJ20250299), Guangxi Natural Science Foundation under Grant (No. 2023GXNSFAA026135), and Key Project of Guangxi Natural Science Foundation (Joint Special Project for Research on Regionally High Incidence Diseases) (No. 2025GXNSFDA069030).

Conflict of interest:

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

See the article:

Han B, Kang M, Huang W, et al. Gut microbiota as master regulators: Mapping gut-organ axes that orchestrate systemic health. TransMed. 2026[2026-09-30]. https://www.sciencedirect.com/science/article/pii/S3117397726000425. DOI: 10.1016/j.tmed.2026.100042