title: Dietary Fiber and Bacterial SCFA Enhance Oral Tolerance and Protect against Food Allergy through Diverse Cellular Pathways.
abstract: The incidence of food allergies in western countries has increased dramatically in recent decades. Tolerance to food antigens relies on mucosal CD103(+) dendritic cells (DCs), which promote differentiation of regulatory T (Treg) cells. We show that high-fiber feeding in mice improved oral tolerance and protected from food allergy. High-fiber feeding reshaped gut microbial ecology and increased the release of short-chain fatty acids (SCFAs), particularly acetate and butyrate. High-fiber feeding enhanced oral tolerance and protected against food allergy by enhancing retinal dehydrogenase activity in CD103(+) DC. This protection depended on vitamin A in the diet. This feeding regimen also boosted IgA production and enhanced T follicular helper and mucosal germinal center responses. Mice lacking GPR43 or GPR109A, receptors for SCFAs, showed exacerbated food allergy and fewer CD103(+) DCs. Dietary elements, including fiber and vitamin A, therefore regulate numerous protective pathways in the gastrointestinal tract, necessary for immune non-responsiveness to food antigens.
authors.affiliation: Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Jian
authors.initials: J
authors.lastname: Tan
authors.affiliation: Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Craig
authors.initials: C
authors.lastname: McKenzie
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Vuillermin
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 HZ Amsterdam, the Netherlands.
authors.forename: Gera
authors.initials: G
authors.lastname: Goverse
authors.affiliation: Department of Pathogens and Immunity, John Curtin School of Medical Research, Australian National University, Building 131, Garran Road, Canberra, ACT 0200, Australia.
authors.forename: Carola G
authors.initials: CG
authors.lastname: Vinuesa
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 HZ Amsterdam, the Netherlands.
authors.forename: Reina E
authors.initials: RE
authors.lastname: Mebius
authors.affiliation: Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; Department of Physiology, Faculty of Medicine, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: laurence.macia@sydney.edu.au.
authors.forename: Laurence
authors.initials: L
authors.lastname: Macia
authors.affiliation: Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; Department of Physiology, Faculty of Medicine, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: charles.mackay@monash.edu.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Mackay
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001419:Bacteria / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D004043:Dietary Fiber / Q000494:pharmacology*; D005232:Fatty Acids, Volatile / Q000378:metabolism*; D005247:Feeding Behavior; D005512:Food Hypersensitivity / Q000276:immunology* / Q000517:prevention & control*; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D007108:Immune Tolerance / Q000187:drug effects*; D007070:Immunoglobulin A / Q000276:immunology; D039001:Integrin alpha Chains / Q000378:metabolism; D008810:Mice, Inbred C57BL; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014801:Vitamin A / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D004043:Dietary Fiber; D005232:Fatty Acids, Volatile; C506481:Ffar2 protein, mouse; C473652:Hcar2 protein, mouse; D007070:Immunoglobulin A; D039001:Integrin alpha Chains; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic; C091367:alpha E integrins; D014801:Vitamin A