Diet prevents the expansion of segmented filamentous bacteria and ileo-colonic inflammation in a model of Crohn's disease

Metwaly, A.; Jovic, J.; Waldschmitt, N.; Khaloian, S.; Heimes, H.; Haecker, D.; Hammoudi, N.; Le Bourhis, L.; Mayorgas, A.; Siebert, K.; Basic, M.; Schwerd, T.; Allez, M.; Panes, J.; Salas, A.; Bleich, A.; Zeissig, S.; Schnupf, P.; Cominelli, F.; Haller, D.

doi:10.1101/2022.07.06.498810

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bioRxiv · 10.1101/2022.07.06.498810

Diet prevents the expansion of segmented filamentous bacteria and ileo-colonic inflammation in a model of Crohn's disease

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Abstract

Crohns disease (CD) is associated with changes in the microbiota, and murine models of CD-like ileo-colonic inflammation depend on the presence of microbial triggers. Increased abundance of unknown Clostridiales and the microscopic detection of filamentous structures close to the epithelium of Tnf {Delta}ARE mice pointed towards segmented filamentous bacteria (SFB), a commensal well-known to induce the maturation of Th17 cell-derived immune responses that is highly implicated in the pathogenesis of IBD. We show that the abundance of SFB strongly correlates with the severity of CD-like ileal inflammation in Tnf {Delta}ARE and SAMP/Yit mice. SFB mono-colonization of germ-free Tnf {Delta}ARE mice confirmed the causal link and resulted in severe ileo-colonic inflammation, characterized by elevated tissue levels of Tnf and Il-17, neutrophil infiltration and loss of Paneth and goblet cell function. Co-colonization of SFB in human-microbiota associated Tnf {Delta}ARE mice confirmed that SFB presence is indispensable for disease development. Screening of 412 ileal and colonic mucosal biopsies from IBD patients using previously published and newly designed human SFB-specific primer sets showed no presence of SFB in human tissue samples. Simulating the protective effect of exclusive enteral nutrition (EEN) by feeding SFB mono-colonized Tnf {Delta}ARE mice EEN-like purified diet antagonized SFB colonization and prevented disease development in Tnf {Delta}ARE mice, clearly demonstrating the important role of diet in modulating this IBD-related but murine pathobiont.

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Metwaly, A., Jovic, J., Waldschmitt, N., Khaloian, S., Heimes, H., Haecker, D., Hammoudi, N., Le Bourhis, L., Mayorgas, A., Siebert, K., Basic, M., Schwerd, T., Allez, M., Panes, J., Salas, A., Bleich, A., Zeissig, S., Schnupf, P., Cominelli, F., Haller, D.. 2022-07-06. Diet prevents the expansion of segmented filamentous bacteria and ileo-colonic inflammation in a model of Crohn's disease. https://doi.org/10.1101/2022.07.06.498810

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