This study aims to reveal the impact of the nuclear transcription regulator Tcf4 loss in the epithelial cells on the gut microbial composition in the small intestine and colon.

The T-cell factor 4 (Tcf4) plays a key role in maintaining intestinal homeostasis, stem cell self-renewal and epithelial cell differentiation. Tcf4 has been identified as a key regulator of Paneth cell function in small intestinal crypts. It controls the expression of antimicrobial peptides and other effector molecules that contribute to the maintenance of the intestinal microbiota and protection against intestinal pathogens. Depletion of Tcf4 in mouse intestinal epithelial cells leads to loss of proliferating cells and dramatic changes in the morophology of the intestinal epithelum. We used the Tcf7l2flox/flox Villin-CreERT2 mouse strain to induce Tcf4 depletion from intestinal epithelial cells by administration of tamoxifen. After few days, we observed rare proliferating cells that have escaped recombination, most of the epithelium is differentiated but functional. Feces were isolated from the distal part of the small intestine and colon 7 days after tamoxifen administration.