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Antibiotic Resistance Genes in Gut Microbiome Rise After Travel Abroad, Study Finds

NEW YORK – International travel can significantly boost the repertoire of antimicrobial resistance, or AMR, genes found in an individual's gut microbial community, new research suggests, with the precise locale influencing the shape of these acquired gut "resistomes."

"We found that which region a traveler visited significantly affected how their composition of resistance genes changed," co-senior and co-corresponding author Gautam Dantas, a researcher affiliated with Washington University's Edison Family Center for Genome Sciences and Systems Biology, explained in an email. "These travel-related resistance gene acquisitions were against both commonly prescribed antibiotics and against last resort antibiotics."

As part of an effort known as the "Carriage of multi-resistant bacteria after travel," or COMBAT, study, Dantas and his colleagues relied on metagenomic sequencing, functional metagenomic analyses, and statistical modeling methods to search for AMR genes in fecal samples from 190 Dutch individuals. They were being followed over time using samples collected before and after trips to four international regions.

The team's findings, published in Genome Medicine on Monday, pointed to a jump in AMR gene prevalence and diversity in the travelers' guts following trips abroad. The newly acquired resistance genes included known and previously undocumented AMR candidates, including genes carried on mobile genetic elements that boosted resistance to a range of antibiotics in follow-up experiments in the lab.

"Together, these findings provide strong support for international travel as a vector of global antimicrobial resistance spread of clinically important resistance genes and highlight the need for broader surveillance of returning travelers’ gut resistance genes," Dantas said.

Starting with fecal swab samples from thousands of participating adults from the Netherlands, the researchers performed shotgun metagenomic sequencing on samples from 190 individuals before and after they traveled to southeastern Asia, southern Asia, northern Africa, or eastern Africa.

From there, they quantified new and known resistance genes with the help of existing databases and functional metagenomics, including experiments aimed at finding the stretches of DNA that prompted antibiotic resistance in Escherichia coli bacteria grown in the lab. In functional metagenomic screening experiments involving more than a dozen antibiotics and 21 sequence libraries, for example, the team uncovered resistance to all but one antibiotic.

The findings revealed "significant travel-related increases in resistance gene acquisition, abundance, and diversity," Dantas explained. In particular, the team identified 121 AMR genes in the gut microbial communities they analyzed, including 56 AMR genes that appeared to be picked up during travel abroad. In contrast, just four AMR genes became less common in the gut microbiomes of participants returning from travel.

The authors noted that "acquisition events were biased towards AMR genes with efflux, inactivation, and target replacement resistance mechanisms," and found that gut resistome features clustered somewhat among travelers who had visited the same countries or regions.

"Even before the COVID-19 pandemic, we knew that international travel was contributing to the rapid global increase and spread of antimicrobial resistance," co-first author Alaric D'Souza, an M.D.-Ph.D. student at Washington University, said in a statement. "But what's new here is that we've found numerous completely novel genes associated with antimicrobial resistance that suggest a worrisome problem on the horizon."