Phase I trial comparing bile acid and short-chain fatty acid alterations in stool collected from human subjects treated with omadacycline or vancomycin

• DOI: 10.1128/aac.01251-24
• Publication Date: 2025-01-17T14:00:16Z
• Authors: Jinhee Jo; Chenlin Hu; Thomas D. Horvath; Sigmund J. Haidacher; Khurshida Begum; M. Jahangir Alam; Kevin W. Garey
• Keywords: Short-chain fatty acid

Omadacycline, an aminomethylcycline tetracycline, has a low propensity to cause Clostridioides difficile infection (CDI) in clinical trials. Omadacycline exhibited reduced bactericidal effect compared with vancomycin on key microorganisms implicated bile acid homeostasis and short-chain fatty acids (SCFAs), components of CDI pathogenesis. The purpose this study was assess SCFA changes stool samples from healthy volunteers given omadacycline or vancomycin. Stool were collected daily 16 volunteers, who oral for 10 days. Daily assessed concentrations using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bile changed significantly over time all subjects (P < 0.01 each acid), causing larger change the primary acids, cholic 0.001) chenodeoxycholic 0.001), secondary acid, lithocholic 0.001). ursodeoxycholic less by than All baseline observed isobutyric = 0.0034), propionic 0.0012), acetic 0.047). Microbial associated use versus also concentrations. Oral produced distinctive metabolomic profile when administered subjects. metabolic findings help further our understanding lower risk properties warrant phase 2 investigations as antibiotic. obtained 10-day course Vancomycin caused omadacycline. mechanistic basis lower-risk This is registered ClinicalTrials.gov NCT06030219.