Gut microbiota dysbiosis and immune responses: insights from IgA nephropathy and inflammatory bowel disease

IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide, and inflammatory bowel disease (IBD) comprises a group of chronic, relapsing inflammatory bowel disorders. Although IgAN and IBD differ in clinical manifestations, both involve interactions among genetic susceptibility, epigenetic abnormalities, and gut microbiota dysbiosis, ultimately pointing to mucosal immune dysregulation and chronic inflammation. They share similar alterations in gut microecology, characterized by a reduction in short-chain fatty acid-producing protective commensals and an increase in pathogenic symbionts. This leads to intestinal barrier disruption and aberrant microbial metabolites, promoting the production of galactose-deficient IgA1 (Gd-IgA1), activating intestinal mucosal immune cells, and driving both local and systemic inflammation. Notably, glucocorticoids (GC) and immunomodulators are common therapeutic agents for both diseases, and effective treatment is accompanied by restoration of the gut microbiota and improvement of immune imbalance. The four currently marketed budesonide enteric-coated capsules employ pH-dependent targeted-release technology and act on different sites ranging from the terminal ileum to the colon to modulate B-cell activation and attenuate local inflammation. IgAN and IBD may be closely related mucosal immune disorders, with immune inflammation associated with gut microbiota dysbiosis may represent a key link between them. Furthermore, upper respiratory tract infection may participate in the development of IgAN through mucosal immunity. The efficacy of tonsillectomy as a therapeutic intervention suggests the existence of crosstalk between the respiratory tract and the kidneys.