title: Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases.
abstract: Gut microbiota has been well recognized in regulation of intestinal homeostasis and pathogenesis of inflammatory bowel diseases. However, the mechanisms involved are still not completely understood. Further, the components of the microbiota which are critically responsible for such effects are also largely unknown. Accumulating evidence suggests that, in addition to pathogen-associated molecular patterns, nutrition and bacterial metabolites might greatly impact the immune response in the gut and beyond. Short chain fatty acids (SCFA), which are metabolized by gut bacteria from otherwise indigestible fiber-rich diets, have been shown to ameliorate diseases in animal models of inflammatory bowel diseases (IBD) and allergic asthma. Although the exact mechanisms for the action of SCFA are still not completely clear, most notable among the SCFA targets is the mammalian G protein-coupled receptor pair of GPR41 and GPR43. In addition to the well-documented inhibition of histone deacetylases activity mainly by butyrate and propionate, which causes anti-inflammatory activities on IEC, macrophages, and dendritic cells, SCFA has recently been implicated in promoting development of Treg cells and possibly other T cells. In addition to animal models, the beneficial effects have also been reported from the clinical studies that used SCFA therapeutically in controlled trial settings in inflammatory disease, in that application of SCFA improved indices of IBD and therapeutic efficacy was demonstrated in acute radiation proctitis. In this review article, we will summarize recent progresses of SCFA in regulation of intestinal homeostasis as well as in pathogenesis of IBD.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, 4.142C Medical Research Building, 301 University Blvd, Galveston, TX, 77555-1019, USA.|Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, 4.142C Medical Research Building, 301 University Blvd, Galveston, TX, 77555-1019, USA.|Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors.forename: Zhanju
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, 4.142C Medical Research Building, 301 University Blvd, Galveston, TX, 77555-1019, USA. yicong@utmb.edu.|Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA. yicong@utmb.edu.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Cong
mesh_terms: D000818:Animals; D005232:Fatty Acids, Volatile / Q000378:metabolism* / Q000627:therapeutic use; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000382:microbiology / Q000503:physiopathology* / Q000628:therapy; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
chemical_list: D005232:Fatty Acids, Volatile; D043562:Receptors, G-Protein-Coupled
keywords: GPCR; IBD; Microbiota; Short chain fatty acids