Abstract
IgA nephropathy (IgAN) represents the most common form of primary glomerulonephritis worldwide, especially in East Asia; even with current treatments, it can lead to end-stage renal disease within 10 years in approximately 20% of adult patients. Genome-wide association studies in IgAN have identified susceptibility genes that are involved in the maintenance of the intestinal epithelial barrier, intestinal inflammation, and the intestinal response to mucosal pathogens, indicating a gut−kidney connection. However, the role of gut microbiota in mediating gut−kidney communication is still underappreciated. Here we highlight current clues that link microbiota with IgAN, and suggest contact points where the microbiota may exert its influence on the onset and progression of IgAN. More specifically, bacterial lipopolysaccharide potentially affects 2 essential components involved in IgAN pathogenesis: the overproduction and hypogalactosylation of IgA1. Short-chain fatty acids can modulate the inflammatory process and protect against renal damage; however, this protection is lost when the intestinal microbiota changes, becomes imbalanced, and becomes dysbiotic. Gut microbiota is also involved in the production of uremic toxins such as indoxyl sulfate and p-cresyl sulfate, which may accelerate kidney disease progression.