Identification of a novel interplay between intestinal bacteria and metabolites in Chinese patients with IgA nephropathy via integrated microbiome and metabolome approaches

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis. The intestinal microbial ecosystem and metabolic network of IgAN have not been systematically analyzed. The present study aims to improve understanding of the gut microbiota and its metabolic capabilities to facilitate the development of diagnostic, therapeutic, and prognostic methods for IgAN. METHODS: We characterized the gut microbiota and metabolic patterns of fecal and serum samples of IgAN patients and healthy controls from the south of China using 16s ribosomal RNA gene sequencing and liquid chromatography-tandem mass spectrometry, respectively, and bioinformatics approaches. RESULTS: We found that the relative abundances of Streptococcus and Enterococcus were higher in IgAN patients, whereas Bacteroidetes and Bacteroides were lower. Changes in the gut microbiota of IgAN affected the metabolism and absorbance of microbiota-associated metabolites, in particular polyunsaturated fatty acids, free amino acid, and oligopeptides, and activated the phenylalanine metabolism pathway, thereby constructing a unique metabolic system of IgAN. We identified six pivotal metabolites, including bilirubin, trimethoprim, stearamide, phenylalanine, cis-9,10-epoxystearic acid, and phosphatidylethanolamine 17:0, that connected the metabolic networks of the gut and blood. Additionally, 5-hydroxyeicosatetraenoic acid and 5-hydroxy-6E,8Z,11Z-eicosatrienoic acid were shown to be associated with the classification of glomerular sclerosis. CONCLUSIONS: We establish a relational network between microbiota, fecal metabolites, and serum metabolites in IgAN. The core microbiota and metabolites identified have promising value in therapeutic applications.