Abstract

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.

Highlights

  • Campylobacter jejuni is a common, potentially commensal member of the avian gut microbiome (Hermans et al, 2012; Humphrey et al, 2014) as well as all warm-blooded animals and the food derived from their tissue; yet, when introduced into the human gut via the ingestion of contaminated food, water, or direct contact with animals, it can cause acute illness as it colonizes the human gut (Coker et al, 2002; Gölz et al, 2014; Kaakoush et al, 2015)

  • We examined whether any significant differences in the microbial diversity of study participants previously enrolled in nonCampylobacter controlled human infection model (CHIM) studies could be observed

  • A C. jejuni CHIM demonstrated that rifaximin chemoprophylaxis did not protect against campylobacteriosis (Rimmer et al, 2018)

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Summary

Introduction

Campylobacter jejuni is a common, potentially commensal member of the avian gut microbiome (Hermans et al, 2012; Humphrey et al, 2014) as well as all warm-blooded animals and the food derived from their tissue; yet, when introduced into the human gut via the ingestion of contaminated food, water, or direct contact with animals, it can cause acute illness as it colonizes the human gut (Coker et al, 2002; Gölz et al, 2014; Kaakoush et al, 2015). Significant mortality and morbidity in pediatric populations in low- to middle-income countries (LMICs), and are caused by adult travelers to those same regions, is caused by C. jejuni-attributed illness (Elaine Scallan et al, 2011; Platts-Mills et al, 2015; Olson et al, 2019). One group of travelers that is often at risk for campylobacteriosis, as well as other enteric diseases, is deployed military (Riddle et al, 2006). Acute diarrhea is the leading infectious disease threat to deployed U.S forces (Riddle et al, 2017). One of the leading etiologies of diarrhea in military populations is C. jejuni, accounting for approximately 10% of all acute diarrheal illness (Connor et al, 2012)

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