title: The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis.
abstract: Regulatory T cells (Tregs) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate Treg responses. Because neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist that regulate the number and function of colonic Tregs. We determined that short-chain fatty acids, gut microbiota-derived bacterial fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice. Our study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Smith
authors.forename: Michael R
authors.initials: MR
authors.lastname: Howitt
authors.forename: Nicolai
authors.initials: N
authors.lastname: Panikov
authors.forename: Monia
authors.initials: M
authors.lastname: Michaud
authors.forename: Carey Ann
authors.initials: CA
authors.lastname: Gallini
authors.forename: Mohammad
authors.initials: M
authors.lastname: Bohlooly-Y
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Glickman
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Garrett
mesh_terms: D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D003092:Colitis / Q000378:metabolism; D003106:Colon / Q000382:microbiology*; D004268:DNA-Binding Proteins / Q000235:genetics; D005232:Fatty Acids, Volatile / Q000008:administration & dosage / Q000378:metabolism*; D005285:Fermentation; D005856:Germ-Free Life; D006706:Homeostasis; D006801:Humans; D054892:Metagenome; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000502:physiology* / Q000637:transplantation
chemical_list: D004268:DNA-Binding Proteins; D005232:Fatty Acids, Volatile; C506481:Ffar2 protein, mouse; C499308:Rag2 protein, mouse; D043562:Receptors, G-Protein-Coupled