2026/02/01 by Hélène Bigonne, Shuhuan Zhai, Jacob Folz +7 · 1 voice
Environmental Science · Biochemistry, Genetics and Molecular Biology · Pharmacology, Toxicology and Pharmaceutics · #Pharmaceutical and Antibiotic Environmental Impacts #Gut microbiota and health #Pharmacogenetics and Drug Metabolism
paper · doi:10.1530/mah-26-0002
openalex publication_date 2026/02/01 · openalex created_date 2026/03/21 · openalex updated_date 2026/07/10
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, could enable 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. Furthermore, correlations between microbial taxa and reaction rates were assessed to establish a link between specific bacteria and probe degradation. Conclusion This functional relevance 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.