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探究人体受控感染模型中宿主肠道微生物群的变化。

Exploring Changes in the Host Gut Microbiota During a Controlled Human Infection Model for .

机构信息

711th Human Performance Wing, Air Force Research Laboratory, Wright-Patterson Air Force Base, Dayton, OH, United States.

Integrative Health and Performance Sciences Division, UES, Inc., Dayton, OH, United States.

出版信息

Front Cell Infect Microbiol. 2021 Aug 31;11:702047. doi: 10.3389/fcimb.2021.702047. eCollection 2021.

Abstract

infection is a leading cause of foodborne disease, common to children, adult travelers, and military populations in low- to middle-income countries. In the absence of a licensed vaccine, efforts to evaluate prophylactic agents are underway. The prophylactic efficacy of a twice-daily, 550 mg dose of the antibiotic rifaximin demonstrated no efficacy against campylobacteriosis in a controlled human infection model (CHIM); however, samples from the CHIM study were utilized to assess how the human gut microbiome responds to infection, and if a 'protective' microbiota exists in study participants not developing campylobacteriosis. Statistically significant, but minor, differences in study participant beta diversity were identified during the challenge period (p = 0.002, R = 0.042), but no significant differences were otherwise observed. Pre-challenge alpha diversity was elevated in study participants who did not develop campylobacteriosis compared to those who did (p < 0.001), but alpha diversity declined in all study participants from the pre-challenge period to post-discharge. Our work provides insight into gut microbiome shifts observed during a CHIM and following antibiotic treatment. This study utilized a high dose of 1.7 x 10 colony-forming units of ; future work could include CHIM studies performed with inocula more closely mimicking natural exposure as well as field studies involving naturally-occurring enteric infections.

摘要

感染是食源性疾病的主要原因,常见于儿童、成年旅行者和中低收入国家的军队人群。在没有许可疫苗的情况下,正在努力评估预防性药物。抗生素利福昔明每日两次、每次 550 毫克的预防性疗效在对照人体感染模型(CHIM)中对弯曲菌病没有疗效;然而,从 CHIM 研究中提取的样本被用于评估人类肠道微生物组对感染的反应,以及在未发生弯曲菌病的研究参与者中是否存在“保护性”微生物组。在挑战期内,研究参与者的β多样性存在统计学上显著但较小的差异(p = 0.002,R = 0.042),但除此之外没有观察到显著差异。与发生弯曲菌病的参与者相比,未发生弯曲菌病的参与者在挑战前的α多样性更高(p < 0.001),但所有参与者的α多样性都从挑战前阶段下降到出院后阶段。我们的工作提供了在 CHIM 期间和抗生素治疗后观察到的肠道微生物组变化的见解。本研究使用了 1.7 x 10 个菌落形成单位的高剂量;未来的工作可以包括更接近模拟自然暴露的接种物的 CHIM 研究以及涉及自然发生的肠道感染的现场研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4edf/8439579/b57d0a3c831f/fcimb-11-702047-g001.jpg

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