Fig. 2. Probiotic-associated reduction in gut resistome is person-specific.
Ten men and women provided stool samples before, after and during 28 d of supplementation with a commercial probiotic supplement; two colonoscopies were performed immediately before supplementation started and on day 21 of supplementation. Metagenomic sequences were analysed using ARG-OAP v.2.0 for the identification of ARGs, subsampled to 2 M of reads and normalized by 16S. a, Experimental design. Individuals were defined as colonization-permissive if they had a statistically significant increase in probiotic load in their lower GI tract mucosa samples according to species-specific quantitative PCR amplification26. b, Bray–Curtis dissimilarity (ARG subtypes) of stool samples to all baseline samples of each individual. The light green shade indicates the supplementation period. Day 1 of supplementation versus baseline P < 0.0001. c, Observed ARG subtypes in stool over time (P = 0.0031). d, Bray–Curtis dissimilarity of ARGs (‘types’) in all lower GI tract endoscopic samples (luminal aspirates and mucosal brushes) collected before (grey) or during supplementation (day 21, green). e, Same as d but based on ARG subtypes and colour-coded according to probiotic colonization permissiveness (purple, n = 6) or resistance (orange, n = 4) and time point (before, light; during, dark). PC2 permissive versus resistant baseline P = 0.0004. f, Per-person Bray–Curtis dissimilarity to baseline calculated in all participants or in the two subsets based on ARG subtypes. Lumen P = 0.052. g,h, Alpha diversity measurements (g), observed ARGs (subtypes) or Shannon diversity index in endoscopic samples (h) of permissive and resistant individuals, compared either to the baseline of each subset or between subsets. In g, lumen, all samples baseline versus during P = 0.035, permissive baseline versus during P = 0.0223. In h, lumen, permissive baseline versus during P = 0.0226. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. Two-way ANOVA and Dunnett’s (a,b) or Sidak’s test (g,h) or two-sided Mann–Whitney U-test (all the rest). The horizontal lines represent the median, the symbols represent the mean, the error bands represent the s.e.m. (b,c) and the whiskers represent the 10–90 percentiles (d–h).