title: The gut-kidney axis in IgA nephropathy: role of microbiota and diet on genetic predisposition.
abstract: Recent data suggest that gut-associated lymphoid tissue (GALT) plays a major role in the development of immunoglobulin A (IgA) nephropathy (IgAN). A genome-wide association study showed that most loci associated with the risk of IgAN are also associated with immune-mediated inflammatory bowel diseases, maintenance of the intestinal barrier and regulation of response to gut pathogens. Studies involving experimental models have demonstrated a pivotal role of intestinal microbiota in the development of IgAN in mice producing high levels of IgA and in transgenic mice overexpressing BAFF, a B-cell factor crucial for IgA synthesis, indicating the role of genetic background, B-cell activity, GALT intestinal immunity and diet. The effect of diet was suggested by pilot studies carried out 30 years ago which showed that a gluten-rich diet induced IgAN in mice and that some patients benefited from a gluten-free diet. A recent experimental model in mice expressing human IgA1 and Fc alpha receptor CD89 reported clinical and histological improvement after a gluten-free diet. Clinical observations have elicited new interest in GALT hyper-reactivity in IgAN patients. In a pilot study, a reduction in proteinuria was attained using an enteric controlled-release formulation of the corticosteroid budesonide targeted to the Peyer's patches at the ileocecal junction. This formulation was tested in the placebo-controlled NEFIGAN phase 2b trial, with a reduction in proteinuria after 9 months of treatment together with stabilization of renal function in patients with persistent proteinuria. In conclusion, the gut-kidney axis modulated by microbiota and diet is a promising target for focused treatment of IgAN in genetically predisposed patients at risk of progression.
authors.affiliation: Fondazione Ricerca Molinette, Regina Margherita Hospital, Turin, Italy. rosanna.coppo@unito.it.
authors.forename: Rosanna
authors.identifier: http://orcid.org/0000-0003-4713-6282
authors.initials: R
authors.lastname: Coppo
mesh_terms: D000818:Animals; D004032:Diet; D020022:Genetic Predisposition to Disease; D005922:Glomerulonephritis, IGA / Q000209:etiology* / Q000235:genetics / Q000628:therapy; D006801:Humans; D007422:Intestines / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology*; D008221:Lymphoid Tissue / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D064307:Microbiota / Q000276:immunology*; D012307:Risk Factors
keywords: Diet; Gluten; Gut-kidney axis; IgA nephropathy; Intestinal immunity; Microbioma