Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA.
Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA
mSphere. 2019 Nov 20;4(6):e00693-19. doi: 10.1128/mSphere.00693-19.
Proton pump inhibitor (PPI) use has been associated with microbiota alterations and susceptibility to infections (CDIs) in humans. We assessed how PPI treatment alters the fecal microbiota and whether treatment promotes CDIs in a mouse model. Mice receiving a PPI treatment were gavaged with 40 mg of omeprazole per kg of body weight during a 7-day pretreatment phase, the day of challenge, and the following 9 days. We found that mice treated with omeprazole were not colonized by When omeprazole treatment was combined with a single clindamycin treatment, one cage of mice remained resistant to colonization, while the other cage was colonized. Treating mice with only clindamycin followed by challenge resulted in colonization. 16S rRNA gene sequencing analysis revealed that omeprazole had minimal impact on the structure of the murine microbiota throughout the 16 days of omeprazole exposure. These results suggest that omeprazole treatment alone is not sufficient to disrupt microbiota resistance to infection in mice that are normally resistant in the absence of antibiotic treatment. Antibiotics are the primary risk factor for infections (CDIs), but other factors may also increase a person's risk. In epidemiological studies, proton pump inhibitor (PPI) use has been associated with CDI incidence and recurrence. PPIs have also been associated with alterations in the human intestinal microbiota in observational and interventional studies. We evaluated the effects of the PPI omeprazole on the structure of the murine intestinal microbiota and its ability to disrupt colonization resistance to We found omeprazole treatment had minimal impact on the murine fecal microbiota and did not promote colonization. Further studies are needed to determine whether other factors contribute to the association between PPIs and CDIs seen in humans or whether aspects of murine physiology may limit its utility to test these types of hypotheses.
质子泵抑制剂 (PPI) 的使用与人类微生物群的改变和易感性感染 (CDI) 有关。我们评估了 PPI 治疗如何改变粪便微生物群，以及治疗是否会在小鼠模型中促进 CDI。在 7 天的预处理阶段、挑战当天和随后的 9 天内，接受 PPI 治疗的小鼠每天用 40mg/kg 的奥美拉唑灌胃。我们发现，用奥美拉唑治疗的小鼠没有被定植。当奥美拉唑治疗与单次克林霉素治疗相结合时，一个笼子的小鼠仍然对定植具有抗性，而另一个笼子的小鼠则被定植。仅用克林霉素治疗然后进行挑战会导致定植。16S rRNA 基因测序分析显示，奥美拉唑在整个 16 天的奥美拉唑暴露期间对小鼠微生物群的结构几乎没有影响。这些结果表明，在没有抗生素治疗的情况下正常具有抗性的小鼠中，单独用奥美拉唑治疗不足以破坏微生物群对感染的抵抗力。抗生素是感染（CDI）的主要危险因素，但其他因素也可能增加一个人的风险。在流行病学研究中，质子泵抑制剂 (PPI) 的使用与 CDI 的发生率和复发有关。在观察性和干预性研究中，PPIs 也与人类肠道微生物群的改变有关。我们评估了 PPI 奥美拉唑对小鼠肠道微生物群结构及其破坏定植抗性的能力。我们发现奥美拉唑治疗对小鼠粪便微生物群的影响很小，并且不会促进定植。需要进一步的研究来确定其他因素是否导致人类中观察到的 PPI 和 CDI 之间的关联，或者是否由于小鼠生理学的某些方面限制了其对这些类型假设的测试能力。
