Microbiota-immune crosstalk in autoimmune disorders: Molecular insights and therapeutic pathways

• Microbiome disruptions linked to immune-mediated inflammatory disorders (IMIDs). • Imbalance in Treg and effector T cells triggers autoimmune diseases. • Gut microbiota shaped by diet, antibiotics, and altered therapies impacts immunity. • AhR modulates host-microbiota interactions, affecting immune and metabolic systems. The human microbiome, consisting of bacteria and their genes residing on and within the body, plays a crucial role in maintaining health and modulating disease. A symbiotic relationship has evolved between host and microbiota, and disruptions in this balance have been linked to immune-mediated inflammatory disorders (IMIDs) such as inflammatory bowel disease (IBD), multiple sclerosis (MS), and rheumatoid arthritis (RA). These conditions are often driven by dysregulation between regulatory T (Treg) cells and pro-inflammatory effector T cells, particularly in genetically predisposed individuals. Factors like diet, antibiotics, and targeted therapies significantly alter gut microbiota composition, potentially influencing immune responses. The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, has emerged as a key modulator of host-microbiota interactions, affecting immunity and metabolism. Advancements in microbial sequencing, notably 16S rRNA analysis, have enabled detailed tracking of gut bacteria. Recent studies highlight molecular mechanisms by which microbiota imbalances contribute to autoimmunity in diseases such as RA, Guillain-Barré syndrome, type 1 diabetes, systemic lupus erythematosus, Sjögren's syndrome, autoimmune liver diseases, and autoimmune thyroid disorders. This review explores the evolving understanding of how microbial dynamics influence immune dysregulation and autoimmunity, offering insights into potential therapeutic targets.