Gut Microbiota and Immunoglobulin A Nephropathy: Exploration of Dietary Intervention and Treatment Strategies

Abstract

Immunoglobulin A nephropathy (IgAN) is a primary glomerular disease characterized by the deposition of IgA. The pathogenesis of it is related to the dysbiosis of gut microbiota. Dysbiosis of gut microbiota influences mucosal immune response and systemic immune system, leading to glycosylation-deficient IgA1 (Gd-IgA1) increasing, which promotes the development of IgAN. Diet plays an important role in regulating gut microbiota and treating IgAN. In this review, we summarize the interplay between gut microbiota and IgAN, and their underlying mechanisms. We also describe the effects of dietary intake on IgAN, as well as the composition of gut microbiota. The progress on IgAN treatment mainly focuses on inhibiting or regulating the immune system. Moreover, therapeutic strategies related to gut microbiota such as dietary intervention, supplement of probiotics and prebiotics, as well as fecal microbiota transplantation (FMT) have shown the possibility of improving IgAN prognosis. Thus, exploration of the gut-kidney axis, the long-term effects of diet and microbiome is necessary to develop more effective treatment strategies.

Keywords: IgAN; diet intervention; gut microbiota; treatment of IgAN.

FIGURE 1

The process of intestinal immunity. The intestinal mucosal barrier is composed of intestinal epithelial cells, a mucus layer, and immune cells, which prevent pathogens and harmful substances from entering the body. The immune cells, including T and B lymphocytes, macrophages, and dendritic cells, embed within the matrix of the payer's patch. (A) When in immune homeostasis, dendritic cells extend dendrites between epithelial cells to sample antigens. The antigens are then broken down and presented to T lymphocytes. These cells are converted into regulatory T cells and migrate to the lamina propria to secrete IL‐10. IL‐10 exerts a suppressive action on immune cells within the lamina propria, so that the gut maintains immune silence, preventing unnecessary inflammation. (B) When the intestinal mucosal barrier is disrupted, the immune cells are activated and regulatory T cells scale down IL‐10 secretion to enable an immune response to proceed. Dendritic cells release inflammatory molecules IL‐6 and IL‐12. Effector T cells migrate to the lamina propria and coordinate an escalation by releasing immune response mediators TNF‐α, interferon (INF) and IL‐17. Meanwhile, B cells are activated and differentiate into plasma cells, which secrete IgA. IgA can neutralize pathogens and toxins, which results in inflammation alleviation.

FIGURE 2

The impact of metabolites on IgAN. Gut metabolites alter in IgAN patients, and these alterations then affect the disease. SCFAs and amino acid metabolites reduce in IgAN patients with inflammation and damage to the intestinal barrier integrity, while arachidonic acid is increased, but also causes inflammation. Enzymes α‐ galactosidase and α‐N‐acetyl galactosidase significantly enriched, resulting in the levels of Gd‐IgA1 increasing. Metabolites aromatic amino acids, such as indole‐3‐propionic acid and indole‐3‐acetic acid, are observed to decline.