Annual Scientific Meeting
Introduction: Travelers’ diarrhea (TD) is a commonly diagnosed acute illness among those visiting tropical and sub-tropical regions with substantial consequences. While antibiotic treatment (with lopermaide) substantially reduces TD symptoms and duration, a growth in concerns about the off-target effects of TD treatment on the impact of resident microflora and the potential adverse effects associated with acquisition of multi-drug resistant organisms (MDRO). To date, most microbiome analyses have studied microbial structure/composition, while the functional capabilities of the gut microbiota remain largely unstudied. We set out to understand the functional properties of the gut microflora in response to TD acquired in diverse geographic regions, associations with different single-dose therapies, MDRO acquisition.
Methods: Fecal samples from USA & UK military service members in 3 continents that presented with acute watery TD were collected at acute presentation (day 1, prior to antibiotics), as well as 7 and/or 21 days following a single-dose of antibiotics (azithromycin (500 mg), levofloxacin (500 mg), or rifaximin (1650 mg) with loperamide). Each sample underwent culture and TaqMan RT-PCR analyses for pathogen detection and a limited set of ESBL-PE genetic probes. Purified DNA from each sample was analyzed using the HumiChip v2.0 microarray which contains over 150,000 DNA probes specific for genes involved in various functional processes including antibiotic resistance, virulence, stress responses, and nutrient metabolism.
Results: In total, 125 Day 1 samples, 64 Day 7 samples, and 105 Day 21 samples were available for analysis from 135 subjects. Ordination analysis revealed that subjects enrolled in each country had distinct functional profiles. While we did not observe overt differences in functional profiles between treatment groups, we observed an increase in functional diversity from day 1 to day 21 in the levofloxacin treatment group, relative to azithromycin and rifaximin groups. Additionally, we noted distinct geographical patterns of resistome patterns at baseline and post-illness, but lesser influence of antibiotic effects on post-treatment functional genomic composition.
Discussion: A thorough understanding of how antibiotics impact the functional properties of the gut microbiota will help inform future treatment options, antibiotic stewardship in TD patients, and the reduction of potential post-infective complications due to MDRO pathobionts.