Gut microbiota-immune axis in the regulation of rheumatoid arthritis: from mechanism to precision probiotic strategies

ABSTRACT Rheumatoid Arthritis (RA) is a progressive autoimmune disorder with substantial global health and economic impacts. Despite advancements in conventional therapies, biologics, and targeted drugs, challenges such as adverse effects, cost, and interindividual heterogeneity underscore the need for safer, precision-based treatments. Notably, emerging evidence highlights the pivotal role of the gut microbiota-immune axis in RA pathogenesis. Affected individuals typically exhibit gut dysbiosis, marked by increased pro-inflammatory taxa and reduced anti-inflammatory species, which disrupts immune homeostasis through Th17/Treg imbalance, molecular mimicry, and compromised gut barrier integrity. These processes drive systemic inflammation, exacerbating both articular destruction and extra-articular manifestations. Probiotics demonstrate therapeutic potential by modulating this axis via microbiota restoration, barrier reinforcement, and immune regulation. Strain-specific effects have been documented in both preclinical and clinical studies, although efficacy varies depending on host genetics, baseline microbiota composition, and intervention protocols—a variability underscoring the need for personalized probiotic selection. This review consolidates current knowledge on gut microbiota-immune crosstalk in RA and explores probiotics as precision therapeutics. Integrating multi-omics (metagenomics, metabolomics) with targeted probiotic strategies could enable the development of personalized interventions. While translational obstacles persist, including mechanistic complexity and limited clinical validation, the gut microbiota-immune axis offers a novel paradigm for RA management. Future priorities include large-scale trials, biomarker discovery, and combinatorial approaches to advancing microbiome-guided precision medicine in autoimmune diseases.