Obesity driven autoimmune dysregulation and its implications in rheumatoid arthritis, lupus, and multiple sclerosis

Obesity, long considered a metabolic disorder, is now recognized as a key driver of immune dysregulation and chronic low-grade inflammation, significantly contributing to the onset and progression of autoimmune diseases. This review critically explores the mechanistic links between obesity and major autoimmune disorders like rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis, highlighting the roles of adipokines, neuroendocrine-immune crosstalk, and chronic systemic inflammation. Special attention is given to the emerging role of gut microbiota dysbiosis in mediating neuroimmune responses through the gut–brain axis. Specific microbiota, such as Akkermansia muciniphila, Prevotella histicola, and Desulfovibrio, are discussed in terms of their contribution to immune modulation, intestinal barrier integrity, and neuroinflammation. Furthermore, we examine how obesity impairs treatment efficacy via pharmacokinetic alterations and propose microbiota-targeted and adipokine-modulating interventions as potential therapeutic strategies. Lifestyle modifications, including diet, physical activity, and bariatric surgery, are also evaluated for their immunomodulatory and clinical benefits. By integrating current evidence from immunometabolism, neuroimmunology, and microbiome research, this review underscores the urgent need for holistic, obesity-informed approaches in autoimmune disease management.