The gastrointestinal pathway leading to autoimmune diseases.

Abstract

The gut microbiota are important in maintaining immune homeostasis through complex interactions with both innate and adaptive immune systems. Disruptions in microbial composition, referred to as dysbiosis, have been increasingly associated with the development and progression of autoimmune diseases. This review explores the key gastrointestinal pathways linking microbiota alterations to immune dysregulation, emphasizing mechanisms that operate from extracellular barrier function to intracellular signaling cascades. Critical processes include impairment of intestinal barrier integrity, modulation of neuroimmune communication via the enteric nervous system and vagus nerve, and the activation of immune responses through molecular mimicry. In addition, pattern recognition receptors, particularly Toll-like receptors, act as essential mediators of host-microbe interactions, integrating microbial signals into pro- or anti-inflammatory immune pathways. These interconnected mechanisms contribute to chronic inflammation, loss of immune tolerance, and systemic autoimmune responses. Emerging evidence highlights the therapeutic potential of targeting the gut microbiota through dietary interventions, probiotics, and fecal microbiota transplantation, as well as through modulation of microbial metabolites and immune signaling pathways. A deeper understanding of these host-microbiota interactions may enable the development of novel, microbiota-directed strategies for the prevention and treatment of autoimmune diseases.