Gut Microbiota Influence on Oral Bioavailability: Implications for Precision Medicine

Gut microbial diversity contributes to individual differences in the absorption and disposition of oral drugs. Gut microbes not only directly metabolize drugs but also affect the expression of transporters, enzymes, and tight junctions that facilitate oral drug absorption and disposition. Results of RNA-Seq, immunohistochemistry and Ussing chamber permeability experiments comparing germ-free mice to those with humanized gut microbiota elucidate the influence of gut microbiota on mechanisms of intestinal drug transport and metabolism. Significant differences were found in the expression of key transporters, specific phase 1 and phase 2 drug-metabolizing enzymes, and genes coding tight junction proteins that are consistent with microbiota-induced decreases in paracellular permeability. The approach and results of this study contribute to a necessary foundation for assessing the role of gut microbiota in precision medicine.