Gut-kidney axis in IgA nephropathy: mechanisms linking microbiota dysbiosis to immune dysregulation, Gd-IgA1 generation, and renal injury.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, with a particularly high prevalence in Asia, and is a leading cause of end-stage renal disease (ESRD). The disease typically presents initially with hematuria and proteinuria, accompanied by progressive decline in renal function. The hallmark pathological feature of IgAN is mesangial IgA1 deposition, and aberrant production of galactose-deficient IgA1 (Gd-IgA1) is considered the key pathogenic driver. Studies have shown that Gd-IgA1 forms immune complexes (ICs) with autoantibodies, which deposit in the glomeruli, elicit inflammatory cascades, and lead to renal tissue injury. Emerging evidence indicates that gut microbiota dysbiosis is closely linked to the pathophysiology of IgAN. Such dysbiosis may promote disease progression by modulating immune responses and disrupting intestinal barrier integrity. Under healthy conditions, the gut microbiota supports host homeostasis through immune regulation and barrier maintenance, whereas dysbiosis may trigger systemic immune activation and contribute to the development of IgAN. This review delineates the relationship between gut microbiota and IgAN, explores the mechanisms of the gut-kidney axis and its relevance to IgAN pathogenesis, and highlights the therapeutic potential of intestinal interventions, including probiotics and fecal microbiota transplantation, for the treatment of IgAN. By synthesizing current evidence, this review aims to provide a theoretical foundation for future research and clinical translation in this field.