Jo Jinhee, Hu Chenlin, Horvath Thomas D, Haidacher Sigmund J, Begum Khurshida, Alam M Jahangir, Garey Kevin W
Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA.
Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
Antimicrob Agents Chemother. 2025 Feb 13;69(2):e0125124. doi: 10.1128/aac.01251-24. Epub 2025 Jan 17.
Omadacycline, an aminomethylcycline tetracycline, has a low propensity to cause infection (CDI) in clinical trials. Omadacycline exhibited a reduced bactericidal effect compared with vancomycin on key microorganisms implicated in bile acid homeostasis and short-chain fatty acids (SCFAs), key components of CDI pathogenesis. The purpose of this study was to assess bile acid and SCFA changes in stool samples from healthy volunteers given omadacycline or vancomycin. Stool samples were collected daily from 16 healthy volunteers, who were given oral omadacycline or vancomycin for 10 days. Daily stool samples were assessed for bile acids and SCFA concentrations using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bile acids changed significantly over time for all subjects ( < 0.01 for each bile acid), with vancomycin causing a larger change in the primary bile acids, cholic acid ( < 0.001) and chenodeoxycholic acid ( < 0.001), and a reduced change in the secondary bile acid, lithocholic acid ( < 0.001). The secondary bile acid ursodeoxycholic acid was reduced less by vancomycin than by omadacycline ( < 0.001). All SCFA concentrations were reduced from baseline with a larger effect observed with vancomycin for isobutyric acid ( = 0.0034), propionic acid ( = 0.0012), and acetic acid ( = 0.047). Microbial changes associated with the use of vancomycin versus omadacycline were also associated with changes in bile acid homeostasis and SCFA concentrations. Oral omadacycline produced a distinctive metabolomic profile compared with vancomycin when administered to healthy subjects. The metabolic findings help further our understanding of the lower CDI risk properties of omadacycline and warrant phase 2 investigations using omadacycline as a CDI antibiotic.
The purpose of this study was to assess bile acid and SCFA changes in stool samples obtained from healthy volunteers given omadacycline or vancomycin. Stool samples were collected daily from 16 healthy volunteers given a 10-day oral course of omadacycline or vancomycin. Vancomycin caused a larger change in the primary bile acids and SCFA concentrations compared with omadacycline. The metabolic findings help further our understanding of the mechanistic basis for the lower-risk properties of omadacycline causing CDI and warrant phase 2 investigations using omadacycline as a CDI antibiotic.
This study is registered with ClinicalTrials.gov as NCT06030219.
奥马环素是一种氨甲基环素四环素，在临床试验中引起艰难梭菌感染（CDI）的倾向较低。与万古霉素相比，奥马环素对参与胆汁酸稳态和短链脂肪酸（SCFAs）（CDI发病机制的关键成分）的关键微生物的杀菌作用减弱。本研究的目的是评估给予奥马环素或万古霉素的健康志愿者粪便样本中胆汁酸和短链脂肪酸的变化。每天从16名健康志愿者收集粪便样本，这些志愿者口服奥马环素或万古霉素10天。使用液相色谱 - 串联质谱法（LC-MS/MS）评估每日粪便样本中的胆汁酸和短链脂肪酸浓度。所有受试者的胆汁酸随时间均有显著变化（每种胆汁酸P<0.01），万古霉素导致初级胆汁酸胆酸（P<0.001）和鹅去氧胆酸（P<0.001）变化更大，而次级胆汁酸石胆酸变化较小（P<0.001）。万古霉素使次级胆汁酸熊去氧胆酸的减少幅度小于奥马环素（P<0.001）。所有短链脂肪酸浓度均从基线降低，万古霉素对异丁酸（P = 0.0034）、丙酸（P = 0.0012）和乙酸（P = 0.047）的影响更大。与使用万古霉素和奥马环素相关的微生物变化也与胆汁酸稳态和短链脂肪酸浓度的变化有关。对健康受试者给药时，口服奥马环素与万古霉素相比产生了独特的代谢组学特征。这些代谢结果有助于进一步了解奥马环素较低的CDI风险特性，并为将奥马环素用作CDI抗生素的2期研究提供依据。
本研究的目的是评估给予奥马环素或万古霉素的健康志愿者粪便样本中胆汁酸和短链脂肪酸的变化。每天从16名接受10天口服奥马环素或万古霉素疗程的健康志愿者收集粪便样本。与奥马环素相比，万古霉素导致初级胆汁酸和短链脂肪酸浓度变化更大。这些代谢结果有助于进一步了解奥马环素导致CDI风险较低的机制基础，并为将奥马环素用作CDI抗生素的2期研究提供依据。
本研究已在ClinicalTrials.gov注册，注册号为NCT06030219。
