A multi-omics study to dissect the role of the gut microbiome in IgA nephropathy risk

Immunoglobulin A (IgA) nephropathy (IgAN) is the most common form of glomerulonephritis, with high prevalence in both Chinese and European populations. IgAN can be mild, or progress to kidney failure in up to 40% of patients within 20-years.

Its pathogenesis has not been fully described, but the fact that IgAN can recur after transplantation hints to a systemic condition caused by factors external to the kidney itself. Recently, mucosal immunity and gut microbiome have been suggested to participate in the pathogenesis of IgAN.

In this project, we will investigate the role of the gut microbiota in mediating the gut-kidney dialogue in IgAN also via the IgA glycome, which plays a crucial role both in mucosal immunity, especially in the gastrointestinal tract, and in the disease initiation and progression.

We will take advantage of three well-characterized samples, including IgAN patients and controls from China and the UK, to: 1. identify microbes and microbial functions (i.e., microbial genes and metabolic pathways they participate to) associating with IgAN and/or with IgA1 and galactose-deficient IgA1 (gd-IgA1) levels; 2. functionally characterize, in a sample of healthy controls and IgAN patients, microbes and microbial functions identified in the previous steps by means of a set of multi-omics in silico analyses; and 3. validate, in vivo, via faecal microbiota transplantation in mouse models, the role played by the gut microbiota in IgAN.