Probiotics in Autoimmune Disease: Strain-specific Mechanisms and Therapeutic Perspectives

The gut microbiota plays a crucial role in human health and is increasingly recognized as a potential therapeutic target for various diseases. Current standard-of-care treatments for autoimmune diseases often include immunosuppressive agents aimed at controlling immune activation and limiting tissue injury rather than solely suppressing autoantibody production. However, systemic immunosuppression can be associated with dose- and duration-dependent adverse effects, underscoring the need to explore adjunctive and alternative therapeutic strategies. This review summarizes the putative mechanisms of action of seven commonly studied probiotic taxa: Lactobacillus, Bifidobacterium, Propionibacterium, butyrate-producing bacteria, yeasts, Enterococcus, and Bacillus. These taxa are presented as representative examples rather than an exhaustive list. The review further compares their commonalities and differences in immunomodulatory features across major autoimmune diseases, including systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and rheumatoid arthritis (RA). We further discuss evidence for potential synergy among probiotic combinations, contrast probiotic-based interventions with conventional immunosuppressive regimens in terms of their putative advantages and limitations, and examine the prospects for precision probiotic strategies alongside current challenges, including strain specificity, dosing and formulation, host heterogeneity, and reproducibility across cohorts. By integrating existing evidence, this review aims to inform the rational development of probiotic-based interventions for autoimmune diseases and provide a framework for future clinical and translational research.