TY - JOUR
T1 - Opposing diet, microbiome, and metabolite mechanisms regulate inflammatory bowel disease in a genetically susceptible host
AU - Pereira, Gabriel Vasconcelos
AU - Boudaud, Marie
AU - Wolter, Mathis
AU - Alexander, Celeste
AU - De Sciscio, Alessandro
AU - Grant, Erica T.
AU - Trindade, Bruno Caetano
AU - Pudlo, Nicholas A.
AU - Singh, Shaleni
AU - Campbell, Austin
AU - Shan, Mengrou
AU - Zhang, Li
AU - Yang, Qinnan
AU - Willieme, Stéphanie
AU - Kim, Kwi
AU - Denike-Duval, Trisha
AU - Fuentes, Jaime
AU - Bleich, André
AU - Schmidt, Thomas M.
AU - Kennedy, Lucy
AU - Lyssiotis, Costas A.
AU - Chen, Grace Y.
AU - Eaton, Kathryn A.
AU - Desai, Mahesh S.
AU - Martens, Eric C.
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/4/10
Y1 - 2024/4/10
N2 - 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 nutrition diet also induces mucus erosion but inhibits inflammation by simultaneously increasing an anti-inflammatory bacterial metabolite, isobutyrate. Our findings underscore the importance of focusing on microbial functions—not taxa—contributing to IBDs and that some diet-mediated functions can oppose those that promote disease.
AB - 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 nutrition diet also induces mucus erosion but inhibits inflammation by simultaneously increasing an anti-inflammatory bacterial metabolite, isobutyrate. Our findings underscore the importance of focusing on microbial functions—not taxa—contributing to IBDs and that some diet-mediated functions can oppose those that promote disease.
KW - dietary fiber
KW - inflammatory bowel disease
KW - microbiome
KW - mucus
UR - http://www.scopus.com/inward/record.url?scp=85188056334&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2024.03.001
DO - 10.1016/j.chom.2024.03.001
M3 - Article
C2 - 38513656
AN - SCOPUS:85188056334
SN - 1931-3128
VL - 32
SP - 527-542.e9
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 4
ER -