Integrated multi-cohort analysis reveals age-dependent signatures of the  gut microbiome in IgA nephropathy
The gut microbiome plays important roles in the host health, and dysbiosis of gut microbiome can be related to disease by irregulated interactions with the host immune system. Immunoglobulin A nephropathy (IgAN) is the most prevalent glomerulonephritis, is characterized by the deposition of IgA in the glomerular mesangium. The dysbiosis of gut microbiome can be associated with the onset and progression of IgAN because of the large amount of secretory IgA is produced in the gut. However, the role of gut microbiome is IgAN is not fully understood. We analyzed the differences of composition and functional genes in the gut microbiome from healthy control and IgAN patients by using metagenome sequencing. Age-dependent shifts of gut microbiome were dysregulated in adult IgAN patients compared to healthy control. Disordered age-dependent shifts were more clearly identified in male than female subjects. Taxonomy and functional genes of gut microbiome were significantly different between the healthy control and IgAN groups in specific age group (male; over the age of 47 years, female; under the age of 44 years). This dysregulated gut ecosystem could be related to immune responses and abnormal IgA production in patients with IgAN. These results can help to understand the potential role of gut microbiome in the pathogenesis of IgAN.