A major mechanism for immunomodulation: Dietary fibres and acid metabolites

作者：Liang Xie, Jahangir Alam, Francine Z. Marques, Charles R. Mackay · 发表于：Seminars in Immunology · 年份：2023 · DOI：10.1016/j.smim.2023.101737 · 被引用次数：97 · 研究领域：Diet and metabolism studies、Gut microbiota and health、Clinical Nutrition and Gastroenterology

Diet and the gut microbiota have a profound influence on physiology and health, however, mechanisms are still emerging. Here we outline several pathways that gut microbiota products, particularly short-chain fatty acids (SCFAs), use to maintain gut and immune homeostasis . Dietary fibre is fermented by the gut microbiota in the colon, and large quantities of SCFAs such as acetate, propionate , and butyrate are produced. Dietary fibre and SCFAs enhance epithelial integrity and thereby limit systemic endotoxemia . Moreover, SCFAs inhibit histone deacetylases (HDAC), and thereby affect gene transcription . SCFAs also bind to ‘metabolite-sensing’ G-protein coupled receptors (GPCRs) such as GPR43, which promotes immune homeostasis. The enormous amounts of SCFAs produced in the colon are sufficient to lower pH, which affects the function of proton sensors such as GPR65 expressed on the gut epithelium and immune cells . GPR65 is an anti-inflammatory Gα s -coupled receptor, which leads to the inhibition of inflammatory cytokines . The importance of GPR65 in inflammatory diseases is underscored by genetics associated with the missense variant I231L (rs3742704), which is associated with human inflammatory bowel disease , atopic dermatitis , and asthma. There is enormous scope to manipulate these pathways using specialized diets that release very high amounts of specific SCFAs in the gut, and we believe that therapies that rely on chemically modified foods is a promising approach. Such ...