The human body contains a diverse community of bacteria, a majority of which is found in the gastrointestinal (GI) tract. Alterations in the GI microbiota have been correlated to diseases such as obesity and irritable bowel syndrome. Secretory diarrhea exhibits alterations on the GI community, and up to 60% of people traveling from developed to developing countries acquire a form of secretory diarrhea know as travelers' diarrhea (TD). Enterotoxigenic E. coli (ETEC) and Norovirus (NV) are the leading cause of bacterial and viral TD, respectively. ETEC expresses two toxins, heat labile toxin (LT) and heat stable toxin (ST), which ultimately lead to secretory diarrhea. The mechanism of noroviral diarrhea is not well understood. Previous studies have shown that an etiologic agent is not identified in as many as 50% of TD cases, suggesting that travel alone may play a role in TD. Presumably, TD causes a shift in bacterial GI communities; however, this has not been studied. <P>The goal of this proposal is to use 16S rDNA metagenomic sequencing and analysis methods to investigate how TD caused by ETEC and NV affects the gut microbiome and to identify shifts in the gut microbiome associated with foreign travel.<P> In Aim 1 I will complete a retrospective study to examine how ETEC-TD alters the gut microbiome by comparing the GI microbial populations in stool samples from healthy travelers to samples from individuals with ETEC-TD and to samples from individuals with unidentified pathogen-TD. I will also develop a PCR assay to rapidly and reliably detect ETEC in human stool samples.<P> Aim 2 will investigate how the microbial populations in the gut shift during NV-TD. In this retrospective study I will compare paired samples where the first sample was collected during an acute diarrheal episode and the second sample, collected from the same individual, was collected after amelioration of diarrheal symptoms. This will allow me to determine how the gut microbiota shifts after an acute episode of NV-TD.<P> In my third Aim, I will complete a prospective study, which seeks to determine the effect of travel on the gut microbiome. I will compare bacterial populations from stool samples, collected at various time points, from healthy individuals traveling to Guadalajara, Mexico. Stool samples will be collected prior to travel, at 7, 14, and 21 days after arrival in Mexico, and upon return to the United States, which will permit me to identify specific changes within the gut microbiome associated with travel to a developing country. <P>This proposal outlines the necessary first steps in understanding how TD affects the gut microbiome. Results from my research could potentially lead to development of preventative treatments and novel therapeutics against TD. )
Public Health Relevance: <br/> Travelers' diarrhea (TD) affects an estimated 11 million people annually. The debilitating form of secretory diarrhea caused by enterotoxigenic Escherichia coli and Norovirus results in a substantial disruption of business and personal travel as well as military service. The proposed studies aim to better understand how TD affects the microbial populations in the gut, potentially leading to effective preventative treatments.