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Poznyak et al. Microbiome Res Rep. 2026;5:3 Page 3 of 23

Table 1. Role of gut microbiota in RA
Potential therapeutic
Bacterial species Impact on RA Mechanism References
approaches
Increased in early RA patients; Triggers inflammatory responses; Probiotics, dietary
Prevotella copri [34-54]
associated with inflammation molecular mimicry modifications
Enhances intestinal
Collinsella aerofaciens permeability; exacerbates Compromises tight junctions; Prebiotics, FMT [55-66]
arthritis elevates inflammatory markers
Relationship to severity varies; Activates Th17 cells; potential
Lactobacillaceae Probiotic supplementation [72-82]
decreases in long-standing RA anti-inflammatory effects
Butyrate-producing Promotes gut health; reduces Regulates immune responses; High-fiber diet, SCFA
bacteria inflammation strengthens intestinal barrier supplementation [64-71]
RA: Rheumatoid arthritis; Th17: T helper 17; FMT: fecal microbiota transplantation; SCFA: short-chain fatty acid.

Lipopolysaccharide (LPS), present in the cell walls of beneficial gram-negative gut bacteria, is known to
activate cytokine cascades and can drive T-cell-mediated arthritis development. However, LPS from specific
bacterial strains can also produce beneficial effects on immune responses. These beneficial effects include
improvements in systemic inflammation, enhanced endothelial function, reductions in oxidative stress, and
modulation of metabolic pathways, collectively contributing to reduced cardiovascular risk . Additionally,
[24]
the interplay between gut microbiota, microRNAs (miRNAs), human leukocyte antigen (HLA) genes, and
intestinal autophagy is crucial in regulating both local and systemic inflammation [25-27] .

The significant role of gut microbiota in RA development suggests that targeting it during the preclinical
stage could offer novel therapeutic options. There has been considerable research into interventions that
modify the intestinal microbiota for RA management, including probiotics, prebiotics, dietary modifications,
antibiotics, fecal microbiota transplantation (FMT), and natural herbal products [28-30] . However, most
investigations have primarily focused on the effects of these treatments in individuals already diagnosed with
clinical RA and in animal models, rather than targeting the preclinical stage. This underscores the need for
further studies to evaluate the efficacy of these interventions during the preclinical phase, aiming to prevent
the onset of RA [31-33] .

PRIMARY COMPONENTS OF GUT MICROBIOME
Specific gut microbial taxa have been implicated in RA pathogenesis through defined immunological and
metabolic mechanisms, with corresponding therapeutic strategies proposed [Table 1].

Prevotella copri
Numerous studies have established a connection between RA and imbalances in the gut microbiome, though
results can vary across different investigations. A notable finding is the increased abundance of the Prevotella
genus, particularly Prevotella copri (P. copri), in individuals with early-stage RA compared to those without
the condition [34,35] . Interestingly, this overrepresentation of P. copri is not found in patients who have
undergone treatment for RA. Advanced metagenome-wide shotgun sequencing has revealed that RA
patients also show increased levels of various other Prevotella species beyond P. copri [36,37] .

The contribution of P. copri to RA development is believed to involve the induction of inflammatory
responses and the phenomenon of molecular mimicry, where microbial proteins resemble host proteins. As
mentioned earlier in this review, the introduction of P. copri into germ-free SKG mice resulted in the
development of arthritis and elevated levels of Th17, interleukin (IL)-23, and IL-1 [38,39] . Similarly, SKG mice
with a microbiota rich in Prevotella from RA patients exhibited worsened arthritis symptoms, accompanied
by increased Th17 cells and related cytokines. Collectively, these findings suggest that an imbalanced gut