Dr Boudaud carried out this research fellowship under the supervision of Dr Mahesh S. Desai at the Luxembourg Institute of Health (LIH).
An animal model was used to mimick the multi-factorial requirement of IBD, by combining: (1) the genetic susceptibility of IL-10-deficient (Il10-/-)mice; (2) the dietary factor by feeding the animals a diet deprived of dietary fiber (Fiber-free, FF); (3) and the microbiome/mucobiome factor with the use of a tractable synthetic microbiota composed of 14 bacterial strains (14SM), 4 of which showing mucolytic activity in vitro. To evaluate the role of mucolytic bacteria in this model, the mice were colonized with either the 14SM or the 10 non-mucolytic strains (10SM).
This work showed that mice developped colitis only if the 3 required variables of the experimental model were combined: IL-10 deficiency (Il10-/-), fiber deprivation, and colonization with the 14SM. Importantly, the mice colonized with the 10 non-mucolytic strains (10SM) did not develop colitis. The immune characterization of the mice showed that the colitis in 14SM-colonized Il10-/- mice initiated with the expansion of NK cells, followed by a T cell response in both the cecum and colon. Fiber deprivation increased the expansion of NK and CD8+ T cells in the cecum and of Th1, Th17 and CD8+ T cells in the colon. Interestingly, 10SM-colonized mice had lower proportions of NK and T cells in the colon but not in the cecum. Furthermore, the 10SM-colonized mice did not show the FF-induced expansion of Th1 cells in the colon. These results were further supported by the high RNA levels of Th1 cytokines, IFNg and IL-12, in 14SM-colonized but not in 10SM-colonized FF-fed mice. Altogether, these data support that the mucobiome within the microbiome mediates FF-induced colitis via the pathological Th1 response in the colon.
These results have been presented in two international conferences by Dr Boudaud and compiled in a preprint publication that is currently under peer-review.
