REVIEW article
Front. Pharmacol.
Sec. Ethnopharmacology
Traditional Chinese Medicine and Plant Metabolites for Rheumatoid Arthritis via Modulating Gut Microbiota: A Scoping Review Evaluating the Transition from Correlation to Causality
Xiadong Yang 1
Rui Niu 1
Tian Lan 2
Shouze Ren 1
Hua Liang 1
Ying Ma 1
Chang Liu 1
1. Graduate School, Heilongjiang University of Chinese Medicine, Harbin, China
2. China Academy of Chinese Medical Sciences Xiyuan Hospital, Beijing, China
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Abstract
Background Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovitis. The "gut-joint axis" proposes gut microbiota and metabolites modulate RA inflammation via mucosal and systemic immune responses. Botanical drugs (Traditional Chinese Medicine, TCM) and plant metabolites offer multi-target potential. However, most studies remain descriptive, demonstrating concurrent microbial shifts but lacking causal designs to verify mechanistic necessity. Objective This scoping review examines TCM and plant metabolite interventions on RA gut microecology (2015–2025), focusing on the "microbiota–metabolite–immune" axis. It aims to classify evidence based on causal design rigor and identify steps to advance research from correlation to causality. Methods We searched PubMed, Embase, and Web of Science (2015–2025). Studies reporting RA outcomes and gut microbiota changes following TCM interventions were included. We established a hierarchical classification system based on design rigor: antibiotic depletion (ABX), fecal microbiota transplantation (FMT), metabolite rescue, and blocking. Evidence was stratified: Level A (Closed-loop: ABX+FMT+rescue/blocking), Level A+ (plus in vitro blocking), Level B (Partial: ABX/FMT alone), and Level C (Correlational). Results Of 25 included studies (24 animal, 1 clinical), only 2 were Level A, 1 Level A+, 3 Level B, and 19 Level C. While TCM improved RA phenotypes and altered microbiota, complete closed-loop verification remains rare. Short-chain fatty acids (SCFAs) show promise but inconsistent trends due to heterogeneity. Bile acids and tryptophan metabolites correlate with reduced inflammation, yet their mechanistic necessity remains largely untested. Conclusion Botanical drugs and plant metabolites demonstrate potential in modulating gut microbiota to improve RA. However, definitive causal links remain underexplored. Future research should prioritize "shortest closed-loop" strategies, including targeted quantification, rescue, and necessity validations. Longitudinal designs and systemic immune metrics are essential to transition from correlations to translatable mechanisms.
Summary
Keywords
fecal microbiota transplantation, Gut Microbiota, Natural Products, Rheumatoid arthritis, Traditional Chinese Medicine
Received
18 January 2026
Accepted
19 February 2026
Copyright
© 2026 Yang, Niu, Lan, Ren, Liang, Ma and Liu. 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: Hua Liang
Disclaimer
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