Intestinal microbiota and its metabolites in IGA nephropathy (A literature review)

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis, diagnosed by the presence of dominant immunoglobulin A deposits in the mesangial matrix of the renal glomeruli. Overproduction of galactose-deficient IgA1, associated with lymphoid tissue of the intestinal mucosa, plays a central role in the disease pathogenesis. The state of the intestinal microbiota, as a major source of IgA1 production, is an important factor of shaping immune response diverse antigenic stimuli. Mucosal hyperreactivity, according to numerous studies, is crucial not only in the development but also in the progression of IgAN.

The widespread introduction of metagenomic DNA sequencing has demonstrated reduced microbial diversity of the intestinal flora in patients with IgAN compared with the healthy individuals. Another important finding is the identification of genomic loci associated with impaired permeability of the intestinal mucosa and the increased susceptibility to inflammatory diseases in IgAN patients. In addition, a relationship has been reported the genetic predisposition to IgAN, which is believed to involve multilocus interaction of risk alleles, and the composition of the microbiota.

In patients with IgAN, a direct correlation was observed between the abundance of specific bacterial families including Actinobacteriaceae, Ruminococcaceae and Bacteroidaceae, and clinical and laboratory parameters such as proteinuria, microhematuria and glomerular filtration rate. In intestinal dysbiosis, the production of key bacterial metabolites, particularly short-chain fatty acids (SCFA) are reduced. These metabolites regulate intestinal barrier permeability, immune response intensity, and antioxidant activity among other processes that may influence the course of the IgAN.

Comprehensive analysis of the intestinal microbiome, including quantitative assessment of specific bacterial species and their metabolites, represents a promising direction for further research and may facilitate the development personalized therapeutic strategies for patients with IgAN.

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