Microbiome in Autoimmune Diseases: Present and Future

The human microbiome shapes immune development and maintains homeostasis. Cumulative evidence has linked dysbiosis to the initiation and progression of autoimmune diseases. In this review, we summarize disease-specific microbial signatures and immunologic axes of rheumatoid arthritis, axial spondylarthritis, systemic lupus erythematosus, inflammatory bowel disease, and type 1 diabetes. Despite the promise of microbiome-based therapeutics, including probiotics, next-generation probiotics, engineered live biotherapeutics, and fecal microbiota transplantation, their translation into clinical practice is limited by heterogeneity, low-biomass contamination issues, and reliance on relative abundance metrics. We highlight the requirement for standardized sampling/analytics and absolute-quantitative approaches, multicenter validation of biomarker panels, and mechanism-driven interventional trials. The integration of microbial, metabolomic, and host immune response aspects is a pivotal step in the transition from association to causation and in the development of precise and safe microbiome-based diagnostics and therapeutics for autoimmune diseases.