Human gut Actinobacteria boost drug absorption by secreting P-glycoprotein ATPase inhibitors.

ABSTRACT: Drug efflux transporters are a major determinant of drug efficacy and toxicity. A canonical example is P-glycoprotein (P-gp), an efflux transporter that controls the intestinal absorption of diverse compounds. Despite a rich literature on the dietary and pharmaceutical compounds that impact P-gp activity, its sensitivity to gut microbial metabolites remains an open question. Surprisingly, we found that the cardiac drug-metabolizing gut Actinobacterium Eggerthella lenta increases drug absorption in mice. Experiments in cell culture revealed that E. lenta produces a soluble factor that post-translationally inhibits P-gp ATPase efflux activity. P-gp inhibition is conserved in the Eggerthellaceae family but absent in other Actinobacteria. Comparative genomics identified ge

SUBMITTER: Kyaw TS 

PROVIDER: S-EPMC11214321 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature