Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, CA, 94550, USA.
School of Natural Sciences, University of California Merced, Merced, CA, 95343, USA.
Sci Rep. 2020 Mar 12;10(1):4571. doi: 10.1038/s41598-020-60982-8.
The gut microbiota is a vast and diverse microbial community that has co-evolved with its host to perform a variety of essential functions involved in the utilization of nutrients and the processing of xenobiotics. Shifts in the composition of gut microbiota can disturb the balance of organisms which can influence the biodisposition of orally administered drugs. To determine how changes in the gut microbiome can alter drug disposition, the pharmacokinetics (PK), and biodistribution of acetaminophen were assessed in C57Bl/6 mice after treatment with the antibiotics ciprofloxacin, amoxicillin, or a cocktail of ampicillin/neomycin. Altered PK, and excretion profiles of acetaminophen were observed in antibiotic exposed animals. Plasma C was significantly decreased in antibiotic treated animals suggesting decreased bioavailability. Urinary metabolite profiles revealed decreases in acetaminophen-sulfate metabolite levels in both the amoxicillin and ampicillin/neomycin treated animals. The ratio between urinary and fecal excretion was also altered in antibiotic treated animals. Analysis of gut microbe composition revealed that changes in microbe content in antibiotic treated animals was associated with changes in acetaminophen biodisposition. These results suggest that exposure to amoxicillin or ampicillin/neomycin can alter the biodisposition of acetaminophen and that these alterations could be due to changes in gut microbiome composition.
肠道微生物群是一个庞大而多样的微生物群落，与宿主共同进化，以执行各种涉及营养物质利用和外源物质处理的重要功能。肠道微生物群组成的变化会干扰生物体的平衡，从而影响口服药物的生物分布。为了确定肠道微生物组的变化如何改变药物处置，在使用抗生素环丙沙星、阿莫西林或氨苄西林/新霉素混合物处理 C57Bl/6 小鼠后，评估了对乙酰氨基酚的药代动力学 (PK) 和生物分布。在暴露于抗生素的动物中观察到对乙酰氨基酚的 PK 和排泄特征发生了变化。抗生素处理动物的血浆 C 明显降低，表明生物利用度降低。尿代谢产物谱显示，在阿莫西林和氨苄西林/新霉素处理的动物中，对乙酰氨基酚-硫酸盐代谢物水平降低。抗生素处理动物的尿粪排泄比也发生了改变。肠道微生物组成的分析表明，抗生素处理动物中微生物含量的变化与对乙酰氨基酚的生物分布变化有关。这些结果表明，阿莫西林或氨苄西林/新霉素的暴露会改变对乙酰氨基酚的生物分布，而这些改变可能是由于肠道微生物群组成的变化。
