Butyrate inhibits type 2 inflammation in eosinophilic chronic rhinosinusitis

• Published in: Biochemical and biophysical research communications Vol. 714; p. 149967
• Main Authors: Toyama, Masatomo, Kouzaki, Hideaki, Shimizu, Takeshi, Hirakawa, Hitoshi, Suzuki, Mikio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25-06-2024
• Subjects: Adult; Allergen; Apoptosis - drug effects; Butyrate; Butyrates - pharmacology; Cells, Cultured; Chronic Disease; Chronic rhinosinusitis; Cytokines - metabolism; Eosinophil; Eosinophilia - drug therapy; Eosinophilia - metabolism; Female; Humans; Immunoglobulin E - immunology; Inflammation - drug therapy; Inflammation - metabolism; Male; Middle Aged; Nasal Polyps - drug therapy; Nasal Polyps - metabolism; Receptors, Cell Surface; Receptors, G-Protein-Coupled - metabolism; Rhinosinusitis - drug therapy; Rhinosinusitis - metabolism; Short-chain fatty acids; Type 2 cytokine; Short-chain fatty acids; Chronic rhinosinusitis; Type 2 cytokine; Eosinophil; Butyrate; Allergen
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2024.149967

Butyrate and other Short-chain fatty acids (SCFAs) are microbial metabolites from Bacteroides and Clostridium species that may suppress type 2 inflammation. However, the mechanisms of SCFAs in the nasal sinuses are not fully understood. We aimed to clarify the in vitro and in vivo roles of SCFAs in eosinophilic chronic rhinosinusitis (ECRS) pathophysiology. We investigated whether SCFAs induced changes in type 2 cytokines, IgE, and apoptosis and the roles of GPR41, GPR43, and histone deacetylase. Analysis of the control subjects demonstrated that butyrate of SCFAs effectively inhibited type 2 cytokine production in PBMCs, ILC2s, and CD4+ T cells and IgE production in CD19+ B cells. In annexin V analysis, butyrate also induced late apoptosis of PBMCs. The butyrate-induced inhibition of type 2 cytokines appeared involved in histone deacetylase inhibition but not in GPR41 or GPR43. In an analysis of ECRS in humans, butyrate inhibited type 2 cytokine production in PBMCs and nasal polyp-derived cells. The butyrate concentration in nasal lavage fluid was significantly decreased in ECRS patients compared to controls and non-ECRS patients. Our findings confirm that butyrate can inhibit type 2 inflammation and may be a potential therapeutic target for ECRS.
•Butyrate suppressed type 2 cytokines secretion in ILC2 and Th2 cells.•Butyrate suppressed type 2 cytokines of polyps and PBMCs in eosinophilic sinusitis.•Butyrate concentration in nasal lavage fluid was low in eosinophilic sinusitis.•GPR41 and GPR43 are not involved in butyrate effects on IL-5 and IL-13 production.•Butyrate may suppress IL-5 and IL-13 production via histone deacetylases.