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

Gut-associated lymphoid tissue is central to the production of galactose-deficient IgA1 (Gd-IgA1), a key factor in immunoglobulin A nephropathy (IgAN). Although no major differences in gut microbiome diversity have been reported across IgAN cohorts, functional alterations in microbial composition may contribute to disease pathogenesis. The study was designed as a cross-sectional study with an embedded prospective cohort component. Forty-eight adults with biopsy-confirmed IgAN-categorized as progressors (eGFR decline > 5 ml/min/1.73 m²/year, n = 23) or nonprogressors (n = 23)-and 23 healthy controls (HC) were recruited. Stool samples underwent metagenomic and functional profiling. Alpha diversity did not differ significantly between IgAN patients and HC. However, butyrate-producing bacteria (Butyrococcus, Agathobacter rectalis) were less abundant in IgAN patients. The sulfoquinovose degradation I pathway, associated with these bacteria, was also reduced. Nucleotide- and nucleoside-biosynthesis pathways were elevated in IgAN. Gd-IgA1 levels correlated with variations in metabolic pathways. Progressors demonstrated enhanced activity in isopropanol biosynthesis, biotin biosynthesis II, and phospholipid biosynthesis pathways. IgAN patients show reduced butyrate-producing bacteria and distinct functional changes in the gut microbiome suggestive of immune activation and inflammation. Progressors exhibit additional metabolic shifts linked to bacterial membrane stabilization.