The Role of Gut Microbiota in Modulating Immune Signaling Pathways in Autoimmune Diseases

The composition of intestinal microbial communities plays a crucial role in maintaining immune homeostasis, influencing both innate and adaptive immune responses. Growing evidence indicates that bidirectional communication between gut bacteria and host immune cells contributes to the development of autoimmune diseases. Disruptions in microbial diversity, known as dysbiosis, are linked to an increased susceptibility to autoimmune disorders such as rheumatoid arthritis (RA), multiple sclerosis (MS), and lupus erythematosus. This review examines the mechanistic connections between microbial dysregulation and abnormal immune activation, focusing on key signaling pathways. Pathways such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Janus kinase/signal transducers and activators of transcription (JAK/STAT), and Toll-like receptor (TLR) networks act as immunological gatekeepers, and their dysregulation-induced by microbial metabolites or shifts in microbial composition-can lead to chronic inflammation and the breakdown of self-tolerance. Additionally, bacterial fermentation products, including short-chain fatty acids (SCFAs), exert immunomodulatory effects by influencing T-cell differentiation and cytokine profiles. Emerging therapeutic strategies targeting microbial restoration, such as precision probiotics, microbiota transplantation, and tailored nutritional interventions, aim to restore immune balance. This review underscores the gut microbiota as a dynamic regulator of immune signaling.