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Study Reveals Microbiome Diversity, Antibiotic Resistance Genes in Isolated Amazon Tribe

NEW YORK (GenomeWeb) – A microbiome study focused on a long-isolated tribe in the Venezuelan Amazon has uncovered the most diverse human microbiomes detected to date.

As they reported in Sciences Advances today, researchers from the US, Venezuela, and Puerto Rico used 16S ribosomal RNA gene sequencing and metagenomic sequencing to characterize bacterial species and genes in gut, oral, and skin microbial communities of nearly three-dozen individuals from the Yanomami tribe in Venezuela — a group that had no known contact with the outside world before being spotted by air in 2008.

The Yanomami gut and skin microbiomes had broader species compositions and gene contents than those in individuals from a Guahibo Amerindian and Malawian populations that still maintain traditional lifestyles, the team found. Diversity differences were even more pronounced when comparing Yanomami microbiomes to those in Americans, whose gut microbial communities had just half of the diversity detected in Yanomami individuals.

Despite their lack of exposure to antibiotics, the Yanomami's gut microbial communities were also home to dozens of antibiotic resistance genes, suggesting bacteria maintain a stockpile of drug-dodging sequences that can be spurred into action after exposure to new chemical challenges.

"Our results suggest that westernization leads to reduction of diversity, to different microbiota compositions, and also to the activation of resistance genes in our bacteria," the study's senior author Maria Gloria Dominguez-Bello, a researcher affiliated with NYU School of Medicine, the Venezuelan Institute for Scientific Research, and the University of Puerto Rico, said during a telephone press briefing this week.

"The implications from this work are relevant to health," she explained, "because immune and metabolic disorders might be related to a degraded microbiome and also because antibiotic resistance is limiting our ability to kill pathogens."

A study published yesterday in Cell Reports echoes the same patterns Dominguez-Bello and her team saw. There, a Canadian- and US-led group described enhanced gut microbial diversity in individuals from two rural Papua New Guinea communities relative to those in individuals from the US — results that the authors of that study attributed to decreased bacterial dispersal in westernized populations.

The incidence of immune and metabolic conditions has increased sharply in westernized countries over the past six decades, prompting speculation that the advent of antibiotics in the 1940s — coupled with a rise in C-section births, dietary changes, and other modernized lifestyle features — may have altered the human-associated microbiota to make individuals more susceptible to such conditions.

Because the Yanomami have not been exposed to antibiotics and other bacteria-altering aspects of modern life, researchers reasoned that the individuals might carry microbial communities that resemble those found in other populations prior to westernization.

The tribe was found by air in 2008 as part of a Venezuela Ministry of Health program to chart locations of remote Amazonian communities and offer them basic medical services, Dominguez-Bello explained.

The individuals reported no prior contact with non-Yanomami individuals, prompting speculation that the tribe may have been largely isolated since their ancestors arrived in the Americas some 11,000 or more years ago.

In 2009, a research team from Venezuela went to the Yanomami village to collect oral, fecal, and skin swab samples from 34 villagers between the ages of 4 and 50 years old. The samples were subsequently sequenced at collaborating centers in the US.

To preserve the privacy of this population, the study's authors did not report the name of the village where Yanomami individuals reside or indicate its location in Venezuela.

Using 16S rRNA gene sequences, the team looked at membership in the Yanomami oral, gut, and skin microbiomes, uncovering species diversity in the gut and skin communities that eclipsed that described in other populations.

"We seem to find a gradient of decreasing diversity," co-author Jose Clemente, a researcher who studies genetics, genomic sciences, and immunology at the Icahn School of Medicine at Mount Sinai, told reporters.

"The Yanomami, who are the least exposed [to westernization], have the highest diversity, followed by the Guahibos and Malawians — who still have very traditional lifestyles, but have already been impacted by the use of antibiotics and the occasional consumption of processed foods — and the US [individuals] who harbor the least amount of diversity," he explained. "Perhaps even minimal exposure to modern practices … can result in a dramatic loss in bacterial diversity."

The microbial diversity in the Yanomami individuals also carried over to bacterial gene repertoires in the fecal and skin samples, which were measured using metagenomic sequencing and used to predict functional capabilities of these microbial communities.

On the other hand, the Yanomami's oral microbiome diversity was similar to that detected in American individuals, though species composition and bacterial gene content differed.

In general, the Yanomami were prone to sharing larger-than-usual proportions of bacteria in microbiomes at each body site, the researchers reported, including potentially beneficial gut microbes. For example, many carried a species called Oxalobacter formigenes that's largely absent in other populations and is believed to ward off kidney stones by degrading a key component called oxalate.

To look at antibiotic susceptibility in the unexposed microbiomes, meanwhile, researchers started by culturing Escherichia coli from Yanomami fecal samples.

All 131 of these strains were vulnerable to a set of 23 antibiotics. But the team suspected this sensitivity might belie silent resistance genes in the bugs. Indeed, DNA analyses on 38 of the E. coli isolates unearthed genes implicated in resistance to eight antibiotics.

Likewise, metagenomic sequences representing gut and oral samples from four Yanomami individuals contained roughly 30 genes involved in resistance to both natural antibiotics — including drugs that resemble compounds produced by soil bacteria — and synthetic antibiotics with no known counterpart in nature.

"By studying the resistome of this incredible, previously uncontacted, antibiotic-naïve Yanomami group, we're now able to establish clearly that antibiotic resistance is a natural feature of the human microbiota that's waiting to be activated or amplified by antibiotic use," Washington University's Gautam Dantas, a co-author on the study, said during this week's press briefing, noting that the finding "emphasizes the need to ramp up our search for new antibiotics so we don't lose this battle against infectious disease."