Reduced butyrate-producing bacteria and altered metabolic pathways in the gut microbiome of immunoglobulin A nephropathy patients

Immunoglobulin A nephropathy (IgAN) is the most prevalent primary glomerular disease globally, with significant differences in its prevalence and presentation across various populations. IgAN is more frequent in Asian populations than in Caucasians. Across European countries estimated IgAN point prevalence is 2.53 per 10 000, ranging from 1.14 per 10 000 in Spain to 5.98 per 10 000 in Lithuania. Current evidence indicates that IgA nephropathy is not caused by a single pathogenic factor but is instead the result of multiple sequential pathogenic "hits." Elevated levels of circulating polymeric galactose deficient IgA1 (Gd-IgA1) and the production of O-glycan-specific antibodies contribute to the formation of IgA1-containing immune complexes. These complexes subsequently deposit in the mesangium, leading to inflammation and glomerular injury. The geographic variation in prevalence and the heritable nature of Gd-IgA1 highlight the potential roles of both environmental factors and genetics in the susceptibility to IgAN. Although the exact production site of Gd-IgA1 remains to be determined, considerable evidence supports that the mucosa-associated lymphoid tissue is responsible for Gd-IgA1 production. Genetic, microbial, and dietary factors, which interact to cause functional changes in the intestinal mucosal immune system, promote the development of IgAN. Most of the studies that focused on gut microbiome characteristics in IgAN were performed in Asia, with several conducted in Europe. Gut microbiome composition and microbial diversity varies in patients with IgAN compared with non-IgAN individuals, among progressors and non-progressors, however, their effect on the course of the disease is not fully understood.