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Exploring Changes in the Host Gut Microbiota During a Controlled Human Infection Model for Campylobacter jejuni.
Frontiers in Cellular and Infection Microbiology ( IF 4.6 ) Pub Date : 2021-08-31 , DOI: 10.3389/fcimb.2021.702047
Blake W Stamps 1, 2 , Janelle Kuroiwa 3, 4 , Sandra D Isidean 3, 4 , Megan A Schilling 3 , Clayton Harro 5 , Kawsar R Talaat 5 , David A Sack 5 , David R Tribble 6 , Alexander C Maue 3, 4 , Joanna E Rimmer 3, 7 , Renee M Laird 3, 4 , Chad K Porter 3 , Michael S Goodson 1 , Frédéric Poly 3
Affiliation  

Campylobacter jejuni 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 C. jejuni 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, R2 = 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 C. jejuni CHIM and following antibiotic treatment. This study utilized a high dose of 1.7 x 105 colony-forming units of C. jejuni; future work could include CHIM studies performed with inocula more closely mimicking natural exposure as well as field studies involving naturally-occurring enteric infections.

中文翻译:

探索空肠弯曲杆菌受控人类感染模型期间宿主肠道微生物群的变化。

空肠弯曲杆菌感染是食源性疾病的主要原因,常见于中低收入国家的儿童、成年旅行者和军人。在没有获得许可的疫苗的情况下,正在努力评估预防剂。在受控的人类感染模型 (CHIM) 中,每天两次 550 毫克剂量的抗生素利福昔明的预防功效表明对弯曲杆菌病没有功效;然而,来自 CHIM 研究的样本被用来评估人类肠道微生物群如何对空肠弯曲杆菌感染做出反应,以及未发生弯曲杆菌病的研究参与者是否存在“保护性”微生物群。在挑战期间确定了研究参与者 beta 多样性的统计学显着差异,但差异很小(p = 0.002,R2 = 0.042),但在其他方面没有观察到显着差异。与发生弯曲杆菌病的参与者相比,未发生弯曲杆菌病的研究参与者的攻击前 alpha 多样性升高(p < 0.001),但所有研究参与者从攻击前到出院后的 alpha 多样性均下降。我们的工作提供了对空肠弯曲杆菌 CHIM 和抗生素治疗后观察到的肠道微生物组变化的洞察。本研究使用了高剂量的 1.7 x 105 空肠弯曲菌集落形成单位;未来的工作可能包括用更接近自然暴露的接种物进行的 CHIM 研究以及涉及自然发生的肠道感染的实地研究。但从攻击前到出院后,所有研究参与者的阿尔法多样性都下降了。我们的工作提供了对空肠弯曲杆菌 CHIM 和抗生素治疗后观察到的肠道微生物组变化的洞察。本研究使用了高剂量的 1.7 x 105 空肠弯曲菌集落形成单位;未来的工作可能包括用更接近自然暴露的接种物进行的 CHIM 研究以及涉及自然发生的肠道感染的实地研究。但从攻击前到出院后,所有研究参与者的阿尔法多样性都下降了。我们的工作提供了对空肠弯曲杆菌 CHIM 和抗生素治疗后观察到的肠道微生物组变化的洞察。本研究使用了高剂量的 1.7 x 105 空肠弯曲菌集落形成单位;未来的工作可能包括用更接近自然暴露的接种物进行的 CHIM 研究以及涉及自然发生的肠道感染的实地研究。
更新日期:2021-08-31
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