Abstract

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis. Intestinal bacteria and their metabolites have been implicated in various diseases. Improved understanding of the gut microbiota and its metabolic capabilities will facilitate development of diagnostic, therapeutic, and prognostic methods for IgAN Method We identified gut microbiota and metabolite biomarkers of IgAN by analyzing microbiomes and metabolomes of fecal and serum samples of IgAN patients and healthy controls using 16s ribosomal RNA gene sequencing and liquid chromatography-tandem mass spectrometry, respectively, and bioinformatics approaches Results We found that relative abundances of Streptococcus and Enterococcus were higher in IgAN patients, whereas Bacteroidetes and Bacteroides were lower. The changes in gut microbiota affected metabolism and absorbance of microbiota-associated metabolites of IgAN patients, in particular polyunsaturated fatty acids, free amino acids and oligopeptides, and activated the phenylalanine metabolism pathway. Also, 5-hydroxyeicosatetraenoic acid and 5-hydroxy-6E,8Z,11Z-eicosatrienoic acid were proved to be associated with the classification of segmental glomerular sclerosis but not 24h urine protein and estimated glomerular filtration rate. Conclusion Our findings demonstrate an interplay between intestinal bacteria and metabolites in IgAN. The identified metabolites may have diagnostic and therapeutic applications.

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