The gut microbiota is a key regulatory hub linking environmental exposure, the mucosal barrier, and joint inflammation, and plays an important role in the pathogenesis and progression of rheumatoid arthritis (RA). Mechanistic studies in this field mainly address two interrelated questions: how RA-associated gut microbiota modulate mucosal immunity and systemic autoimmunity through strain-level variation, niche competition, and metabolic remodeling; and how disease stage, host immune status, and drug exposure reciprocally reshape gut microbial structure and function. Accordingly, this review follows the framework of “anti-inflammatory/pro-inflammatory microbial niches—microbiota-derived metabolites—immune cell homing and migration” to summarize recent advances in the role of gut microbiota and their derivatives in RA onset, progression, and therapeutic response. Focusing on disease-stage-specific remodeling of gut functional ecology, we discuss how short-chain fatty acids, tryptophan-derived indoles, bile acids, succinate, and other microbial effector molecules regulate RA immunopathology through regulatory T cells (Treg), regulatory B cells (Breg), type 17 T helper cells (Th17), and IL-17-producing T follicular helper cells (Tfh17), dendritic cells, fibroblast-like synoviocytes, and osteoclasts. We also highlight intestinal antigen sampling, autoantibody generation, immune cell trafficking, and synovial reactivation as key links in the gut–joint axis. This review aims to shift RA microbiome research from taxonomic profiling toward stage-specific functional ecological analysis, providing a basis for risk stratification, therapeutic response prediction, and microbiota-based adjunctive interventions.

Ulcerative colitis (UC), a chronic inflammatory bowel disease, is closely associated with disturbances in the gut microbiota. Natural polysaccharides, owing to their unique “indigestibility” and prebiotic properties, represent a potential strategy for intervening in UC by remodeling the gut microecology. This review summarizes the mechanisms by which natural polysaccharides alleviate UC through modulation of the gut microbiota, with a particular focus on the structure–activity relationship between the structural features of natural polysaccharides and their microbiota-regulating functions. Analytical studies indicate that polysaccharides with distinct structures can be recognized and degraded by specific carbohydrate-active enzymes (CAZymes) in the gut microorganisms, leading to the targeted enrichment of beneficial genera such as Roseburia, Lactobacillus, and Akkermansia, while simultaneously suppressing pro-inflammatory genera such as Escherichia–Shigella and Helicobacter. This structure-dependent microbial remodeling ultimately enhances the production of key metabolites and exerts comprehensive therapeutic effects, including repair of the intestinal barrier, suppression of excessive inflammation, and alleviation of oxidative stress, via activation of signaling pathways such as AMP-activated protein kinase (AMPK) and nuclear factor erythroid 2-related factor 2 (Nrf2) and inhibition of pathways such as nuclear factor kappa-B (NF-κB). By exploring the paradigm of “Structure–Decoding–Conversion–Effect” based on precise microecological regulation of polysaccharide structures, this paper provides a crucial theoretical foundation and design strategy for developing targeted microecological interventions.

Traditional Chinese medicine (TCM) polysaccharides are important active components of traditional Chinese medicine, and their anti-inflammatory, immunomodulatory, and mucosal barrier protective effects have attracted widespread attention. Since most traditional Chinese medicine polysaccharides are difficult to be completely digested and absorbed in the gastrointestinal tract, their interventional effects on respiratory diseases may be closely related to the selective utilization by gut microorganisms and the regulation of the gut–lung axis. Therefore, the structural and functional interactions between traditional Chinese medicine polysaccharides and gut microbiota have gradually become an important direction in traditional Chinese medicine pharmacology and microecology research. This review mainly explores two core questions: first, how traditional Chinese medicine polysaccharides that can act on the gut–lung axis drive candidate gut bacteria and metabolic networks; second, how polysaccharide-driven candidate bacteria and metabolic networks regulate pulmonary infection, allergic inflammation, chronic airway injury, and fibrosis through the intestinal mucosal barrier, immune cell reprogramming, and cross-organ signal transmission. Accordingly, this narrative mechanistic review examines selected preclinical studies on traditional Chinese medicine polysaccharides regulating the gut–lung axis, focusing on summarizing the continuous mechanisms by which different polysaccharides promote the proliferation of related microbial communities and metabolite production through selective feeding of gut microorganisms, stabilize intestinal mucosal immunity, and exert pulmonary interventional effects. This review aims to deepen the understanding of the interaction mechanisms among traditional Chinese medicine polysaccharides, microorganisms, and the host, provide some reference for establishing a mechanistic evidence framework for gut–lung axis research and screening potential active polysaccharides with relevant structures and microbiota effects.