Short-chain fatty acids (SCFAs) and the “Regulatory” B-cell: why fiber diet may reduce relapse in IgA vasculitis

Dear Editor, IgA vasculitis (IgAV), formerly known as Henoch–Schönlein purpura, is a generalized endothelial inflammation in small vessels characterized by IgA1-mediated immune complex deposition within vessel walls. The pathogenesis involves defective glycosylation of IgA1, the formation of self-reactive antibodies against carbohydrate-containing molecules, and subsequent antibody-mediated endothelial injury[1]. Clinically, IgAV manifests with palpable purpura, arthralgia, gastrointestinal involvement, and IgA nephropathy, the latter being the primary cause of long-term morbidity. Annually, about 3–27 children per 100 000 are affected by IgAV, with fewer cases in adults. Diagnosis relies on clinical assessment, supported by tissue examination revealing IgA deposition upon immunofluorescence. The treatment for IgAV primarily addresses symptoms as they arise, involving supportive therapy and immunosuppressants for severe organ disease. However, there is limited guidance on lifestyle or dietary strategies that could prevent relapse or modulate the underlying immune dysregulation[2]. This gap has led to growing interest in adjunctive interventions, such as dietary fiber–mediated modulation of gut-derived metabolites, that may influence immune responses in IgAV. Dietary fiber intake increases the production of short-chain fatty acids (SCFAs), particularly butyrate, which might serve as a promising adjunctive immunomodulatory approach for IgAV. This dietary intervention works by modifying the gut microbiota, thereby increasing the fermentation of complex carbohydrates into bioactive SCFAs[3]. Butyrate exerts its effects through the inhibition of histone deacetylase and the activation of G-protein–coupled receptor signaling, which collectively suppresses pro-inflammatory immune responses. At the molecular level, butyrate promotes the expansion of IL-10–producing regulatory B (Bregg) cells and limits excessive IgA synthesis, thereby reducing immune complex–mediated vascular injury[4]. Preclinical and early translational evidence suggests potential benefit not only for IgAV but also for other autoimmune conditions, including inflammatory bowel disease, rheumatoid arthritis, and systemic lupus erythematosus[5]. Overall, high-fiber dietary interventions that increase SCFA availability may serve as a novel, low-risk adjunctive strategy to improve immune regulation and reduce relapse in IgAV. Preclinical and early clinical studies show that high-fiber diets reliably increase SCFA levels in humans, affecting immune cells. In a high-SCFA dietary intervention, plasma butyrate levels increased from 2.02 to 2.85 µmol/l, significantly altering lymphocyte profiles. While IgAV–specific clinical outcomes are lacking, animal models show reduced autoimmune activity and improved disease outcomes[6]. Despite the strong immunomodulatory properties of SCFAs such as butyrate, several challenges limit their clinical use in IgAV. Evidence in IgAV is insufficient, as most data come from animal models or other autoimmune diseases, creating uncertainty about translation to humans. Individual differences in gut microbiota affect SCFA production and response, leading to inconsistent outcomes. Gastrointestinal side effects, unclear optimal dosing, and lack of standardized guidelines further limit its usage. Additionally, low public awareness and socioeconomic barriers may reduce accessibility[7,8]. In conclusion, dietary fiber–derived SCFAs, particularly butyrate, represent a promising adjunctive strategy to reduce relapse and improve immune regulation in IgAV. Future efforts should focus on conducting large, IgAV-specific clinical trials to establish optimal dosing and efficacy. Increasing public and physician awareness about the role of diet in immune modulation, providing access to high-fiber foods, and integrating SCFA-based interventions into conventional treatment may improve overall prognosis. Targeted research and implementation can help translate this mechanistic evidence into practical and effective therapies for patients with IgAV. This letter to the editor adheres to the Transparency in the Reporting of Artificial Intelligence in Research (TITAN) guideline[9].