{"doi":"10.1101/2022.10.13.512142","title":"Human gut Actinobacteria boost drug absorption by secreting P-glycoprotein ATPase inhibitors","abstract":"SUMMARY 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 reports that P-gp expression depends on the microbiome, the mechanisms responsible and their physiological relevance remain unclear. Surprisingly, we found that the cardiac drug-metabolizing gut Actinobacterium Eggerthella lenta increases drug absorption in mice through post-translational inhibition of P-gp ATPase efflux activity. P-gp inhibition is conserved in the Eggerthellaceae family but absent in other Actinobacteria. Comparative genomics identified genes associated with P-gp inhibition. Finally, activity-guided biochemical fractionation coupled to metabolomics identified a cluster of isoflavonoids produced by E. lenta related to plant-derived P-gp inhibitors. These results highlight the unexpected overlap between diet- and microbiome-derived compounds, and the importance of considering the broader relevance of the gut microbiome for drug disposition beyond first-pass metabolism. One Sentence Summary The gut bacterium Eggerthella lenta secretes inhibitors of P-glycoprotein ATPase activity, accelerating drug absorption.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":304578,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9597,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":620612,"name":"Moriah Sandy","orcid":"0000-0002-9914-624X","position":1,"is_corresponding":false},{"id":827097,"name":"Kai Trepka","orcid":"0000-0002-8672-6317","position":2,"is_corresponding":false},{"id":998003,"name":"Janice JN Goh","orcid":null,"position":3,"is_corresponding":false},{"id":998004,"name":"Kristie B. Yu","orcid":null,"position":4,"is_corresponding":false},{"id":998005,"name":"Vincent DiMassa","orcid":null,"position":5,"is_corresponding":false},{"id":301874,"name":"Elizabeth N. Bess","orcid":"0000-0003-0349-0423","position":6,"is_corresponding":false},{"id":301873,"name":"Jordan E. Bisanz","orcid":"0000-0002-8649-1706","position":7,"is_corresponding":false},{"id":36356,"name":"Peter J. Turnbaugh","orcid":"0000-0002-0888-2875","position":8,"is_corresponding":false},{"id":235404,"name":"Than S. Kyaw","orcid":"0000-0002-7933-8615","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T00:32:32.651796Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}