{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T04:33:57Z","timestamp":1792557237888,"version":"4.5.0"},"posted":{"date-parts":[[2025,8,28]]},"group-title":"Microbiology","reference-count":55,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health","award":["R01HD110367"],"award-info":[{"award-number":["R01HD110367"]}]},{"award":["AI111738"],"award-info":[{"award-number":["AI111738"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"crossref","award":["47674"],"award-info":[{"award-number":["47674"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The vaginal microbiome plays a critical role in maintaining immune and epithelial homeostasis in the female reproductive tract. Bacterial Vaginosis (BV) is deleterious to female health, causing the loss of beneficial\n                  <jats:italic>Lactobacillus<\/jats:italic>\n                  species, overgrowth of anaerobic taxa, changes in vaginal pH, breakdown of protective mucins and epithelial barriers, and activation of the immune system. Treatment with gel-based antibiotics (Metronidazole or Clindamycin) resolves BV for 85% of patients, but 50% of those cases recur, indicating a need to identify strategies for overcoming antibiotic resistance and achieving a more durable response. Here, we developed a systems biology approach termed\n                  <jats:italic>Microbiome Pharmacology Analysis<\/jats:italic>\n                  to characterize the antibiotic potential of vaginal microbes, their metabolites and functions, via computational fusion of human cohort multi-omics and post-drug perturbation transcriptomic profiles. We focused on Clindamycin and Metronidazole as candidate drugs and screened 780 vaginal microbiome-drug mimicry candidates to identify candidate taxa and metabolites with antibiotic potential. We demonstrate experimentally that\n                  <jats:italic>Lactobacillus crispatus<\/jats:italic>\n                  -derived Hydroxyisocaproate (HICA) selectively kills\n                  <jats:italic>Gardnerella vaginalis<\/jats:italic>\n                  and that HICA enhances epithelial barrier integrity in a human vagina-on-a-chip system. Our work demonstrates the first use of\n                  <jats:italic>Pharmacobiome Analysis<\/jats:italic>\n                  , for discovering novel, selective antibiotic metabolites for BV with implications for charting the full pharmacologic potential of the vaginal microbiome.\n                <\/jats:p>","DOI":"10.1101\/2025.08.28.672927","type":"posted-content","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T04:30:16Z","timestamp":1756441816000},"source":"Crossref","is-referenced-by-count":1,"title":["Identifying a Vaginal Microbiome-Derived Selective Antibiotic Metabolite via Microbiome Pharmacology 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Doran","family":"Brubaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R.","family":"Muwonge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elly","family":"Katabira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean M","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda 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