Extended Data Fig. 10: Six-day treatment of mice with the non-antibiotics chlorpromazine, clomiphene, clotrimazole, terfenadine, and zafirlukast results in mild effects on the microbiome and no change on E. coli levels.

a-c) S. Tm load in the spleen, liver, and mesenteric lymph nodes (mLN) of mice colonized with a) Com20, number of mice per treatment: DMSO: 8, clotrimazole: 7, zafirlukast: 8, chlorpromazine: 8, terfenadine: 7; b) SPF mice, DMSO: 9, clotrimazole: 9, zafirlukast: 9, chlorpromazine: 9, terfenadine: 9, clomiphene: 9, and c) humanized (Hum) mice, DMSO: 8, terfenadine: 6. Days post infection (d.p.i.): 1 day a,b) or 4 days c). Black horizontal lines indicate detection limits. Red horizontal lines represent the mean the above stated biological replicates, with vertical bars showing ± 1s.e.m. P values from one-tailed Wilcoxon test with Benjamini-Hochberg correction. d-f) Effect size and adjusted P values from linear models of the abundance of Com20 members d), native microbiota ASVs e), and human-derived-microbiota ASVs f) in mice 6 days after drug treatment compared to untreated controls. Models were adjusted for species abundance on day 0. The dashed horizontal line marks the significance threshold of 0.1. Point shape indicates whether an ASV was significantly different (TRUE) from controls. g-h) E. coli levels in the feces of g) SPF mice, number of mice per treatment: DMSO: 10, clotrimazole: 8, zafirlukast: 9, chlorpromazine: 9, terfenadine: 9, clomiphene: 7; or h) humanized mice, DMSO: 13, terfenadine: 12, measured by selective plating on MacConkey agar, before and 6 days after drug treatment. Red horizontal bars show the mean of the above number of biological replicates, with vertical bars representing ± 1 s.e.m. Adjusted P values from a two-tailed Wilcoxon test > 0.1 in all cases. NS: not significant; P > 0.05.

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