Effects of traditional Chinese medicine polysaccharides on rheumatoid arthritis through gut microbiota modulation: a systematic review in animal models

Background Traditional Chinese medicine polysaccharides (TCMPs) are promising therapeutic candidates for rheumatoid arthritis (RA), known for their efficacy and low toxicity. Acting as potent gut microbiota modulators, TCMPs may alleviate RA by reshaping microbial communities and their metabolic outputs. Methods This systematic review followed PRISMA guidelines. We searched PubMed, Web of Science, and Embase up to April 7, 2025, for relevant animal studies. Results From an initial pool of 282 records, nine studies meeting the inclusion criteria were analyzed, involving polysaccharides from six single herbs and one compound formula. The results demonstrated that TCMPs significantly alleviated RA symptoms, including paw swelling and arthritis scores, and improved bone quality metrics. Regarding gut microbiota modulation, TCMPs induced changes in nine phyla (e.g., Patescibacteria, Desulfobacterota, Firmicutes) and 65 genera. At the genus level, 37 taxa (including Dubosiella , Faecalibaculum , Bifidobacterium ) increased in abundance post-treatment, while 20 decreased. The results for 8 genera were inconsistent across studies. Notably, the abundance of Lactobacillus was reported to increase in four of the included studies. These microbial shifts correlated with reduced pro-inflammatory cytokines (e.g., IL-1β, TNF-α), improved RA clinical and bone parameters, and elevated levels of short-chain fatty acids (SCFAs), particularly butyrate and propionate. Correlation analyses identified Romboutsia and Lactobacillus as negatively associated with RA severity. Mechanistically, TCMPs enriched beneficial genera, enhanced SCFA production, suppressed NF-κB and JAK/STAT3 pathways, upregulated tight junction-related genes, and inhibited NLRP3 inflammasome activation via microbiota-derived metabolites, collectively forming a “microbiota–metabolite–host” regulatory network. Conclusion This review demonstrates that TCMPs alleviate RA in animal models by modulating gut microbiota to enrich beneficial bacteria, suppress pathogens, enhance intestinal barrier function, and regulate immune homeostasis via the gut–joint axis, with SCFAs playing a pivotal role. Given the low methodological quality and high heterogeneity of included studies, future research should prioritize rigorous design, multi-omics integration, and clinical translation. Systematic review registration https://www.crd.york.ac.uk/prospero/ , identifier CRD420251053482.