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. 2021 May 28;12:3105. doi: 10.1038/s41467-021-23460-x

Fig. 4. GUT-108 strains decreased colitis in Il10−/− mice colonized with human fecal microbiota.

Fig. 4

a Schematic overview of experimental design. On day 1, mice were inoculated with a human stool previously verified to induce aggressive colitis in gnotobiotic Il10−/− mice. Therapeutic application of GUT-108 or PBS control started after 2 weeks. After 4 weeks necropsies were performed, and tissue samples were collected for analysis. b Bacterial species whose abundance significantly changed in the gut microbiome of mice that received therapeutic application of GUT-108 compared to PBS control mice. Differences in relative species abundance between the two treatments is expressed on a Log10 scale. Strains with decreased (red) or increased (blue) relative abundance are indicated. GUT-108 strains are indicated in black. *P < 0.05 value using the two-sided Benjamini–Hochberg corrected Wilcoxon test. c Serial fecal lipocalin-2 levels were measured using ELISA after 2 (before start of GUT-108 or PBS therapy), 3 and 4 weeks. Dots indicate individual mice data. Mann–Whitney unpaired two-tailed t-test. Bars indicate Mean ± SE, *P < 0.05, ***P < 0.001, N.S. indicates not significant. N = 11/group. d Blinded histologic scoring assessed the level of inflammation for different parts of the intestine, including the distal ileum (Ile), cecum (Ce), proximal- (Pc) and distal- (Dc) colon, rectum (Re), and combined (Ce + Pc + Dc + Re). Dots indicate individual mice data. Mann–Whitney unpaired two-tailed t-test. Bars indicate Mean ± SE. Unpaired two-tailed t-test was performed on the data. *P < 0.05, ***P < 0.001, NS not significant. N = 11/group. e Representative distal colonic photomicrographs of H&E-stained tissue showing colonic tissues 2 weeks after starting therapeutic treatment of humanized Il10−/− mice with GUT-108 or PBS. The experiment was repeated independently with similar results for each animal in the GUT-108 (N = 11) or PBS (N = 11) group. The bar in the picture indicates 100 µm; Hu + GUT-108 refers to humanized Il10−/− mice treated with GUT-108; Hu + PBS refers to humanized Il10−/− mice that received PBS as a placebo control. f Induction of protective fecal metabolites by therapeutic GUT-108 treatment beginning at 2 weeks after the induction of inflammation by human stool. Week 4 represents 2 weeks of therapeutic treatment. Hu+GUT-108 refers to humanized Il10−/− mice treated with GUT-108; Hu + PBS refers to humanized Il10−/− mice that received PBS buffer. DCA deoxycholic acid, LCA lithocholic acid, IPA indole-3-propionic acid. Two-way ANOVA and adjusted P-values were calculated by the multiple comparisons test. Bar indicates Mean ± SE. N.S. not significant; *: adjusted P < 0.05; **: adjusted P < 0.01; ***: adjusted P < 0.001. Source data and calculated P-values are provided as a Source Data file.