Extended Data Fig. 9: Duloxetine bioaccumulation, community assembly and host response.
From: Bioaccumulation of therapeutic drugs by human gut bacteria
a, E. rectale relative abundance in transfer assays based on 16-S amplicon reads. b, E. rectale relative abundance as in a but normalized with respect to equal abundance of each of the five species in the inoculum mixture. Mean values from biological triplicates are shown. c, Duloxetine depletion in community assembly assay. Dashed line indicates mean of control. n = 6 (3 biological replicates, 2 measurements per sample); overlaid box plots show the interquartile range (IQR), the median value and whiskers extending to include all the values less than 1.5 × IQR away from the 1st or 3rd quartile, respectively. d, Metabolic cross-feeding between S. salivarius and E. rectale. Shown are the results of untargeted metabolomics analysis (FIA–MS) of supernatants collected during the growth of S. salivarius in GMM with duloxetine and the subsequent growth of E. rectale in the cell-free conditioned medium. Shown are the profiles of the ions that increased during S. salivarius growth and decreased during E. rectale growth, implying cross-feeding. Ions showing similar pattern in the drug-free solvent (DMSO) control were filtered out. Mean intensities from three biological replicates are shown. e, Dose dependent effects of duloxetine on muscular function in wild type C. elegans animals. Larval stage four (L4) worms were incubated in LB medium in the presence of duloxetine at the indicated concentrations. Each bar represents the mean of six independent experiments, each performed with two technical replicates, ± SD. P values mark difference to the no-drug control, estimated using one-way ANOVA followed by correction for multiple pair-wise comparisons (Tukey’s test). f, Duloxetine concentration in the C. elegans behaviour assay (n = 6; 3 biological replicates, 2 measurements per sample). Overlaid box plots show the interquartile range (IQR), the median value and whiskers extending to include all the values less than 1.5 × IQR away from the 1st or 3rd quartile, respectively
