Extended Data Fig. 7: Phages that target cytolytic E. faecalis reduce ethanol-induced liver disease in gnotobiotic mice.
From: Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease
a–h, C57BL/6 germ-free mice were colonized with faeces from two cytolysin-positive patients with alcoholic hepatitis (faeces from one patient were also used in Fig. 2). The mice were then fed oral isocaloric (control) or chronic–binge ethanol diets, and gavaged with control phages against C. crescentus (1010 PFUs) or a cocktail of 3 or 4 different phages that target cytolytic E. faecalis (1010 PFUs), one day before an ethanol binge. a, Percentage of TUNEL-positive hepatic cells. b, Representative oil red O-stained liver sections. c, d, Hepatic levels of mRNAs that encode the inflammatory cytokine Cxcl2, and Acta2 (a marker of activated hepatic stellate cells). e, Faecal CFUs of Enterococcus. f, Faecal samples were collected and 16S rRNA genes were sequenced. PCoA based on Jaccard dissimilarity matrices shows no significant differences in the faecal microbiota of mice gavaged with control phage and phages that target cytolytic E. faecalis in each group. g, h, Serum levels of ethanol and hepatic levels of Adh1 and Cyp2e1 mRNAs did not differ significantly among colonized mice after ethanol feeding. Scale bar, 100 μm. Results are expressed as mean ± s.e.m. (a, c–e, g, h). P values were determined by two-way ANOVA with Tukey’s post hoc test (a, c–e, g, h) or PERMANOVA followed by FDR procedures (f). All results were generated from at least three independent replicates. The exact group size (n) and P values for each comparison are listed in Supplementary Table 10. *P < 0.05, ***P < 0.001.
