A major mechanism for immunomodulation: Dietary fibres and acid metabolites. (March 2023)

• Record Type: Journal Article
• Authors: Xie, Liang; Alam, Md Jahangir; Marques, Francine Z.; Mackay, Charles R.
• Is Part Of: Seminars in immunology. Volume 66(2023)
• Publication Date: 2023-03
• Subjects: SCFAs Short-chain fatty acids -- DP Degree of polymerization -- IBD Inflammatory bowel disease -- DSS Dextran sulfate sodium -- T2D Type 2 diabetes -- CVDs Cardiovascular diseases -- BP Blood pressure -- HMOs Human milk oligosaccharides -- CRC Colorectal cancer -- CAZymes Carbohydrate-active enzymes -- RS Resistant starch -- AX Arabinoxylan -- HDACs Histone deacetylases -- GPCRs G-protein coupled receptors -- HIF-1α Hypoxia-induced factor 1α -- Treg Regulatory T cell -- TH1 Type 1 helper T cells -- TH17 Type 17 helper T cells -- TH2 Type 2 helper T cells -- NOD Non-obese diabetic -- HAMS High amylose maze starch -- HAMSA HAMS conjugated with acetate -- HAMSB HAMS conjugated with butyrate -- HAMSP HAMS conjugated with propionate; Short-chain fatty acids (SCFA) -- GPR43 -- GPR65 -- Proton sensing -- Dietary fibre -- Gut microbiota/microbiome; Immunology -- Periodicals; Allergy and Immunology -- Periodicals; Immunity -- Periodicals; Immunologie -- Périodiques; Electronic journals; 616.079
• DOI: 10.1016/j.smim.2023.101737
• Languages: English
• ISSNs: 1044-5323

Abstract

Abstract: 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 Gαs -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 an approach includes high SCFA-producing diets, which we have shown to decrease numerous inflammatory western diseases in mouse models. These diets operate at many levels - increased gut integrity, changes to the gut microbiome, and promotion of immune homeostasis, which represents a new and highly promising way to prevent or treat human disease. Highlights: Lacking dietary fibre underlies the prevalence of western diseases. Gut microbiota ferments dietary fibre into acids, i.e. short-chain fatty acids. Fermentation of dietary fibre and production of acids shapes the gut microbiota. Dietary fibre and acids modulate immune homeostasis. Novel medicinal food based on fibre may be effective against western diseases.