biostudies-literaturePereira GVNIDDK NIH HHSHorizon 2020 Marie Skłodowska-Curie ActionsNational Institute of Diabetes and Digestive and Kidney DiseasesNHLBI NIH HHSFNRNational Heart Lung and Blood InstituteFulbright AssociationNIGMS NIH HHSKenneth Rainin foundation527-542.e9https://www.ebi.ac.uk/biostudies/studies/S-EPMC11064055biostudies-literatureUnknown32(4)Inflammatory bowel diseases (IBDs) are chronic conditions characterized by periods of spontaneous intestinal inflammation and are increasing in industrialized populations. Combined with host genetics, diet and gut bacteria are thought to contribute prominently to IBDs, but mechanisms are still emerging. In mice lacking the IBD-associated cytokine, interleukin-10, we show that a fiber-deprived gut microbiota promotes the deterioration of colonic mucus, leading to lethal colitis. Inflammation starts with the expansion of natural killer cells and altered immunoglobulin-A coating of some bacteria. Lethal colitis is then driven by Th1 immune responses to increased activities of mucin-degrading bacteria that cause inflammation first in regions with thinner mucus. A fiber-free exclusive enteral nCell host & microbeOpposing diet, microbiome, and metabolite mechanisms regulate inflammatory bowel disease in a genetically susceptible host.PMC11064055P01 HL149633T32 GM007544R01 DK125445R01 DK118024Desai MSShan MKim KFuentes JZhang LWillieme SGrant ETPereira GVPudlo NAEaton KADenike-Duval TBoudaud MAlexander CSingh SSchmidt TMChen GYKennedy LBleich AWolter MMartens ECTrindade BCCampbell AYang QDe Sciscio ALyssiotis CAfalseOpposing diet, microbiome, and metabolite mechanisms regulate inflammatory bowel disease in a genetically susceptible host.Inflammatory bowel diseases (IBDs) are chronic conditions characterized by periods of spontaneous intestinal inflammation and are increasing in industrialized populations. Combined with host genetics, diet and gut bacteria are thought to contribute prominently to IBDs, but mechanisms are still emerging. In mice lacking the IBD-associated cytokine, interleukin-10, we show that a fiber-deprived gut microbiota promotes the deterioration of colonic mucus, leading to lethal colitis. Inflammation starts with the expansion of natural killer cells and altered immunoglobulin-A coating of some bacteria. Lethal colitis is then driven by Th1 immune responses to increased activities of mucin-degrading bacteria that cause inflammation first in regions with thinner mucus. A fiber-free exclusive enteral n2024-01-01T00:00:00Z2024 Apr2026-06-03T01:19:20.96Z2025-07-13T03:05:11.33ZS-EPMC110640553851365610.1016/j.chom.2024.03.001