Fig. 5: Digoxin increases the susceptibility of gnotobiotic mice colonized with human microbial communities to infection with WT S. Tm.
From: Identification of medication–microbiome interactions that affect gut infection
a, Experimental design. A TH17-inducing defined community of human gut isolates or pooled human faecal samples were used to colonize GF C57BL/6NTac Nramp1+/+ recipient mice. Mice were treated with PBS (n = 4) or digoxin (n = 5) as in Fig. 1c. Twelve hours after the final treatment dose, mice were euthanized or infected with WT S. Tm. b, Ileal expression of selected marker genes at day 0 in mice colonized with the TH17-inducing defined community. c, Schematic for pooling human-microbiome samples. d, Ileal expression of Il22 at day 0 in mice colonized with TH17-inducing pooled human gut microbiomes (GF n = 5, PBS n = 4, digoxin n = 4). Ordinary one-way analysis of variance (ANOVA) followed by Tukey’s multiple comparisons test was used to compare multiple groups. e, Expression of Il17a in digoxin-pretreated (n = 4) or PBS-pretreated (n = 4) ex-GF mice. f, Expression of Defb39 in digoxin-pretreated (n = 5) or PBS-pretreated (n = 5) ex-GF mice. g,h, Ex-GF Nramp1+/+ mice pretreated with PBS (n = 5) or digoxin (n = 5) were infected with WT S. Tm. g, Pathogen burden in the faeces and in the contents of the ileum, caecum and colon at 4 dpi. h, Gene expression of S. Tm-responsive inflammatory marker genes in ileal tissue from mice colonized with pooled human communities at 4 dpi. Two-sided Mann–Whitney test was used to compare two groups in b,e–h. Bars are geometric mean values in b,d–f,h, and median in g.
