Drug and the dynamic microbiome

Drug and the dynamic microbiome

Xenobiotics Shape the Physiologyand Gene Expression of the Active Human Gut Microbiome

The gut microbiome is highly active, similar to nutrient-rich productive systems ► Firmicutes dominate the active and damaged subsets of the gut microbiome ► Both antibiotics and host-targeted drugs rapidly alter the active gut microbiome ► Xenobiotics induce genes for drug metabolism, drug resistance, and stress response

The human gut contains trillions of microorganisms that influence our health by metabolizing xenobiotics, including host-targeted drugs and antibiotics. Recent efforts have characterized the diversity of this host-associated community, but it remains unclear which microorganisms are active and what perturbations influence this activity. Here, we combine flow cytometry, 16S rRNA gene sequencing, and metatranscriptomics to demonstrate that the gut contains a distinctive set of active microorganisms, primarily Firmicutes. Short-term exposure to a panel of xenobiotics significantly affected the physiology, structure, and gene expression of this active gut microbiome. Xenobiotic-responsive genes were found across multiple bacterial phyla, encoding antibiotic resistance, drug metabolism, and stress response pathways. These results demonstrate the power of moving beyond surveys of microbial diversity to better understand metabolic activity, highlight the unintended consequences of xenobiotics, and suggest that attempts at personalized medicine should consider interindividual variations in the active human gut microbiome.