Fig. 1

Knockout of transcription factor 7-like 2 (Tcf7l2) gene affects intestinal epithelial renewal and microbiota dynamics. A Fluorescence micrographs of T-cell factor 4 (Tcf4, green) and proliferating cell nuclear antigen (PCNA, red) localization in the small intestine of wild-type Tcf7l2^wt/wt/VillinCreER^T2 (Tcf7l2^wt/wt) and knockout Tcf7l2^flox/flox /VillinCreER^T2 (Tcf7l2^flox/flox) mice, with or without antibiotic (ATB) treatment, over time after tamoxifen administration. Greyscale images are shown in Additional file 8: Supplementary Figure S1. The insets show increased magnification of the framed areas. Scale bar: 50 μm. B Quantification of small intestinal crypts with the ability to renew the intestinal epithelium. Samples were stained with an antibody against the stem cell marker olfactomedin 4 (Olfm4; green signal; scale bar: 50 μm). Olfm4-positive crypts were manually counted in the three fields of view in the duodenum (duo), jejunum (jej) and ileum (ile) of the four biological replicates. The statistical significance between the individual groups in the corresponding part of the small intestine was determined using the one-way ANOVA test; *p < 0.05; **p < 0.01. C Histological sections show the mislocalization and expression changes of the Paneth cell markers lysozyme (Lyz) and regenerating islet-derived 3 beta (Reg3b) seven days after tamoxifen administration. Yellow arrowheads indicate Lyz-positive cells on the villi; white arrowheads show that the crypt bases in the Tcf4⁺ epithelium are not positive for Reg3b, while they produce Reg3b in the Tcf4-deficient epithelium. Scale bar: 50 μm. D Analysis of the microbiome composition in the distal small intestine of Tcf7l2^wt/wt and Tcf7l2^flox/flox mice. The pie chart shows the bacterial distribution in Tcf4-proficient mice (a solid black point on the outer perimeter of the chart) and Tcf4-deficient mice (an empty black ring). The principal component analysis (PCA) below the diagram illustrates the variance between bacterial populations, indicating shifts in the microbiota associated with the Tcf7l2 status. E Kaplan–Meier survival curves for Tcf7l2 knockout mice treated with either antibiotics or water. Statistical significance (p = 0.034) shows that the antibiotic treatment increases survival. The number of mice used in the experiment is indicated (n), and the graph depicting mouse weight after recombination is shown in Additional file 8: Supplementary Figure S2C