Epidemiology and associated microbiota changes in deployed military personnel at high risk of traveler's diarrhea

Abstract

Travelers' diarrhea (TD) is the most prevalent illness encountered by deployed military personnel and has a major impact on military operations, from reduced job performance to lost duty days. Frequently, the etiology of TD is unknown and, with underreporting of cases, it is difficult to accurately assess its impact. An increasing number of ailments include an altered or aberrant gut microbiome. To better understand the relationships between long-term deployments and TD, we studied military personnel during two nine-month deployment cycles in 2015-2016 to Honduras. To collect data on the prevalence of diarrhea and impact on duty, a total of 1173 personnel completed questionnaires at the end of their deployment. 56.7% reported reduced performance and 21.1% reported lost duty days. We conducted a passive surveillance study of all cases of diarrhea reporting to the medical unit with 152 total cases and a similar pattern of etiology. Enteroaggregative E. coli (EAEC, 52/152), enterotoxigenic E. coli (ETEC, 50/152), and enteropathogenic E. coli (EPEC, 35/152) were the most prevalent pathogens detected. An active longitudinal surveillance of 67 subjects also identified diarrheagenic E. coli as the primary etiology (7/16 EPEC, 7/16 EAEC, and 6/16 ETEC). Eleven subjects were recruited into a nested longitudinal substudy to examine gut microbiome changes associated with deployment. A 16S rRNA amplicon survey of fecal samples showed differentially abundant baseline taxa for subjects who contracted TD versus those who did not, as well as detection of taxa positively associated with self-reported gastrointestinal distress. Disrupted microbiota was also qualitatively observable for weeks preceding and following the incidents of TD. These findings illustrate the complex etiology of diarrhea amongst military personnel in deployed settings and its impacts on job performance. Potential factors of resistance or susceptibility can provide a foundation for future clinical trials to evaluate prevention and treatment strategies.

A Pilot Study of the Effect of Deployment on the Gut Microbiome and Traveler’s Diarrhea Susceptibility

“…This suggests that despite high levels of TD while on deployment, most subjects had few changes in their gut microbiome that persisted after deployment was complete. This is consistent with data from a recent longitudinal deployment microbiome study (Walters et al, 2020). Instead and with few exceptions, prior to, and/or after, deployment the subjects were separated into three distinct metacommunities identified by utilizing Dirchelet Multinomial Mixture modeling ( Figure 3A).…”

“…Still, it could be that the lineage occupies a fundamental niche in the guts of those predisposed to TD. Other unclassified Ruminococcaceae genera have been recently associated with TD, specifically Ruminococcaceae UCG-013 which was differentially abundant in a deployed military population in Honduras (Walters et al, 2020). Further work will confirm the role unclassified Ruminoccocaceae play in the development of diarrhea, but their presence could predispose those in metacommunity 2 to TD in future deployments.…”

“…Subjects that consented to fecal sampling were asked to provide samples before and after deployment. Additionally, after deployment, at their post-deployment briefing, individuals were also asked to answer a short survey (Supplemental Figure S1) similar to that in our previously published work (Walters et al, 2020) related to their broad deployment location (also known as unified combatant commands), dietary choices, diarrhea before, during, and after deployment, and the number of episodes of diarrhea during each of these three phases. Deployment locations were defined as AFRICOM (Africa), CENTCOM (Middle East), EUCOM (Europe), INDOPACOM (Indo-Pacific region), NORTHCOM (North America), and SOUTHCOM (South America).…”

“…While identification of specific pathogens is certainly of interest, within military populations or any traveler, understanding if a specific microorganism or microbiome population can predict susceptibility or resilience to diarrhea is potentially more desirable to prevent the problem before it could become an impediment to performance. Previously, a study within the US Air Force (USAF) at an air base in Honduras identified microbial taxa that were potentially predictive of the development of TD within the study population (Walters et al, 2020). However, in this study, samples were collected once the population was deployed and all subjects were deployed to a singular location.…”

Enterotoxigenic Escherichia coli (ETEC) vaccines: Priority activities to enable product development, licensure, and global access

“…Recent data demonstrating that dmLT can be administered parenterally to improve intestinal immune responses opens new opportunities for subunit-based ETEC vaccines. Enhanced studies of the fecal microbiome may also point to an important role of intestinal microbiota in ETEC susceptibility [85] , [86] . These data may enable an evaluation of the interplay between vaccination and potential modifications of microbiome inducing a less susceptible profile.…”