Tai Yu-Hsien, Kao Cheng-Yen, Zhang Ya-Ping, Chiou Yu-Jing, Chiu Huai-Hsuan, Thuy Tran Thi Dieu, Liao Hsiao-Wei
Department of Pharmacy, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Institute of Microbiology and Immunology, College of Life Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Talanta. 2025 Feb 1;283:127094. doi: 10.1016/j.talanta.2024.127094. Epub 2024 Oct 24.
Investigation of drug-microbial interactions has gained prominence due to the increasing need to study pharmacomicrobiomics. Previous research has revealed the microbiome's role in drug metabolism, influencing efficacy, bioavailability, and toxicity. Several potential interactions have reported between drugs and microbes, including bioaccumulation, biotransformation, and the influence of drugs on microbial growth. To facilitate the investigation of drug-microbial interactions, in this study, we present an integrated platform and procedure for investigating drug-microbial interactions, focusing on biotransformation, bioaccumulation, metabolomics, exometabolomics, lipidomics, and exolipidomics. To illustrate the feasibility of this platform, we examined the interactions between digoxin and Lactiplantibacillus pentosus (L. pentosus), revealing previously unknown interactions. Although the growth of L. pentosus was unaffected by digoxin, metabolomics, exometabolomics, lipidomics, and exolipidomics analyses revealed digoxin's impact on metabolites and lipids inside and outside L. pentosus. Additionally, we utilized a validated liquid chromatography-mass spectrometry quantification platform to evaluate digoxin biotransformation and bioaccumulation levels by L. pentosus. After accurately quantifying digoxin in the supernatant and pellet, we determined that approximately 8.7 % of digoxin was biotransformed by L. pentosus. Exolipidomics analysis further supported digoxin biotransformation, identifying digoxigenin and its metabolites. These findings elucidate the potential impact of L. pentosus on digoxin metabolism, underscoring the importance of considering microbial interactions in pharmacological research. We anticipate that the integrated platform could assist in more pharmacomicrobiomics studies and uncover unknown drug-microbial interactions.
由于研究药物微生物组学的需求不断增加，药物与微生物相互作用的研究变得日益重要。先前的研究揭示了微生物群落在药物代谢中的作用，影响药物疗效、生物利用度和毒性。药物与微生物之间已报道了几种潜在的相互作用，包括生物累积、生物转化以及药物对微生物生长的影响。为了便于研究药物与微生物的相互作用，在本研究中，我们提出了一个用于研究药物与微生物相互作用的综合平台和程序，重点关注生物转化、生物累积、代谢组学、胞外代谢组学、脂质组学和胞外脂质组学。为了说明该平台的可行性，我们研究了地高辛与戊糖片球菌之间的相互作用，揭示了以前未知的相互作用。尽管戊糖片球菌的生长不受地高辛的影响，但代谢组学、胞外代谢组学、脂质组学和胞外脂质组学分析揭示了地高辛对戊糖片球菌内外代谢物和脂质的影响。此外，我们利用经过验证的液相色谱-质谱定量平台来评估戊糖片球菌对地高辛的生物转化和生物累积水平。在准确测定上清液和沉淀中的地高辛含量后，我们确定约8.7%的地高辛被戊糖片球菌生物转化。胞外脂质组学分析进一步支持了地高辛的生物转化，鉴定出了地高辛配基及其代谢物。这些发现阐明了戊糖片球菌对地高辛代谢的潜在影响，强调了在药理学研究中考虑微生物相互作用的重要性。我们预计该综合平台可协助开展更多的药物微生物组学研究，并发现未知的药物与微生物相互作用。
