Quantitative chemical activity profiling reveals gut microbiome modulations

Objective The gut microbiome catalyzes biotransformation reactions that influence intestinal absorption as a basis of microbiome-host interactions. A better understanding of microbiota biotransformation capacity, and its modulation in dysregulated states, would enable the prediction of individual responses to drugs and toxins and improve safety assessment. Methods Here, we used chemical activity profiling to quantify biotransformation capacity modulations in rat gut microbiome ex vivo following oral exposure to eight drugs and dietary compounds: tobramycin, colistin, acesulfame potassium, saccharin, bovine serum albumin (BSA), meropenem, doripenem, and daidzein. We implemented an approach involving inoculation with metabolic probes during microbiota fermentations and measured their degradation rates. Results In most exposure groups, we observed no modulation of microbiota biotransformation capacity, however, we detected significant modulations in biotransformation rates after exposure to meropenem, doripenem and tobramycin. Interestingly, common patterns of biotransformation capacity were observed in the gut microbiomes from rats exposed to carbapenems and partially shared in microbiomes exposed to tobramycin. These results aligned well with prior metagenomic and metabolomic findings. Further, correlations between microbial taxa and reaction rates were assessed to establish a link between specific bacteria and probe degradation. Conclusions This functionally relevant strategy revealed modulations of microbiota biotransformation capacity, as induced by in vivo exposures. Significance statement This research provides a framework to predict how exposure to drugs or dietary compounds modulates the gut microbial capacity to biotransform xenobiotics, which is crucial for understanding individual drug responses and host-microbiome interactions.