Opposing diet, microbiome, and metabolite mechanisms regulate inflammatory bowel disease in a genetically susceptible host

Gabriel Vasconcelos Pereira, Marie Boudaud, Mathis Wolter, Celeste Alexander, Alessandro De Sciscio, Erica T. Grant, Bruno Caetano Trindade, Nicholas A. Pudlo, Shaleni Singh, Austin Campbell, Mengrou Shan, Li Zhang, Qinnan Yang, Stéphanie Willieme, Kwi Kim, Trisha Denike-Duval, Jaime Fuentes, André Bleich, Thomas M. Schmidt, Lucy KennedyCostas A. Lyssiotis, Grace Y. Chen, Kathryn A. Eaton, Mahesh S. Desai* (Main author), Eric C. Martens*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)527-542.e9
JournalCell Host and Microbe
Volume32
Issue number4
Early online date18 Mar 2024
DOIs
Publication statusPublished - 10 Apr 2024

Keywords

  • dietary fiber
  • inflammatory bowel disease
  • microbiome
  • mucus

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