Dietary Fiber and Bacterial SCFA Enhance Oral Tolerance and Protect against Food Allergy through Diverse Cellular Pathways
Jian Tan,
Craig McKenzie,
Peter J. Vuillermin,
Gera Goverse,
Carola G. Vinuesa,
Reina E. Mebius,
Laurence Macia,
Charles R. Mackay
Affiliations
Jian Tan
Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
Craig McKenzie
Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
Peter J. Vuillermin
School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia
Gera Goverse
Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 HZ Amsterdam, the Netherlands
Carola G. Vinuesa
Department of Pathogens and Immunity, John Curtin School of Medical Research, Australian National University, Building 131, Garran Road, Canberra, ACT 0200, Australia
Reina E. Mebius
Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 HZ Amsterdam, the Netherlands
Laurence Macia
Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
Charles R. Mackay
Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
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.
