Amazon jungle of Venezuela in 2009, they marveled at the
chance to study the health of people who had never been
exposed to Western medicine or diets. But much to their
surprise, these Yanomami's gut bacteria have already evolved a diverse array of antibiotic-resistance genes, according to a new study, even though these mountain people had never ingested antibiotics or animals raised with drugs. The find suggests that microbes have long evolved the capability to fight toxins, including antibiotics, and that preventing drug resistance may be harder than scientists thought.
The human gut harbors trillions of bacteria, collectively known as the microbiome. Several recent studies have found that people in industrialized nations host far fewer types of microbes than hunter-gatherers in Africa, Peru, and Papua New Guinea, for example. This is intriguing as the absence of diverse bacteria has been linked to obesity, diabetes, and many autoimmune disorders, such as allergies, Crohn's disease, celiac disease, and colitis.
So, when microbiologist Maria Dominguez-Bello of the New York University School of Medicine in New York City learned that army personnel aboard a helicopter had spotted Yanomami living in an uncharted village in the
mountains of southern Venezuela in 2008, she immediately
requested permission to study these uncontacted people before they were exposed to Western medicines and diets and would, therefore, lose diverse microbes. "This information is important; because it will give us some light on what are the bacteria we are missing, what bacteria are we losing," she says. "We need to get a better understanding of the microbiota in this community of hunter-gatherers before they are lost."
The Yanomami health care workers who were the first to contact the remote villagers in a medical expedition in 2009
collected bacteria from the mouths, skin, and feces of 34 of
the 54 Yanomami for the researchers. They prescribed
medicines to some children with respiratory ailments but have not published the name of the village to protect these people from further contact. After 2 years of getting the proper permits and an 11-month delay when Dominguez-Bello's lab in New York was closed by damage from Hurricane Sandy, she and her colleagues eventually
sequenced the Yanomami gut bacteria RNA in their labs to
compare it with samples from industrialized Americans and
rural Guahibo Amerindians of Colombia and farmers from
Malawi. When they compared the genetic sequences, they found that the Yanomami harbor "significantly higher diversity than other populations," including high amounts of
Prevotella, Helicobacter, Oxalobacter, and Spirochaeta, for example, that are absent or significantly reduced in
industrialized humans. The medical workers also documented that although these Yanomami had high levels of parasites, they were healthy and did not suffer from autoimmune disorders, diabetes, high blood pressure, or heart disease, the team reports today in Science Advances.
Meanwhile, microbiologist Gautam Dantas of Washington University in St. Louis interrogated the Yanomami gut and oral samples for the presence of antibiotic-resistance genes.
Dantas's graduate student Erica Pehrsson cloned bacterial DNA from these samples and tested whether any of their genes could inactivate natural and synthetic antibiotics. They found that the Yanomami gut bacteria had nearly 60 unique genes that could turn on and rally to fend off antibiotics, including a half-dozen genes that could protect the bacteria from synthetic antibiotics. This is particularly troubling, Dantas says, because researchers have thought that it would take bacteria longer to evolve resistance to humanmade
antibiotics not found naturally in the soil.
The medical team's interviews with these Yanomami villagers found they were never given drugs or exposed to food or water with antibiotics. Instead, Dantas suggests that the Yanomami gut bacteria have evolved an armory of methods to fight a wide range of toxins that threaten them— just as our ancestors and other primates have done to fight dangerous microbes. For example, the Yanomami bacteria may already have encountered toxins that occur naturally in their environment that are similar in molecular structure to modern antibiotics, but have yet to be discovered by scientists. Or, gut bacteria in humans have evolved a generalized mechanism for detecting certain features shared by all antibiotics—including the synthetic ones designed by scientists—and so can mount a defense against new threats.
The discovery is troubling because it suggests that "antibiotic resistance is ancient, diverse, and astonishingly widespread in nature—including within our own bodies," says anthropologist Christina Warinner of the University of Oklahoma in Norman, who is not a co-author. "Such findings and their implications explain why antibiotic resistance was so quick to develop after the introduction of therapeutic antibiotics, and why we today should be very concerned about the proper use and management of
antibiotics in both clinical and agricultural contexts."
Other researchers are also interested in exploring the
function of the diverse bacteria found in the Yanomami, to see if these microbes train their children's immune systems early and if they are protective against autoimmune diseases on the rise in industrialized populations. One type of gut
bacteria, Oxalobacter, found in the Yanomami is already known to protect humans from the formation of kidney stones. "I think these missing microbes are at the root of many Western diseases," says microbiologist Justin Sonnenburg of Stanford University in Palo Alto, California, co-author of the forthcoming book The Good Gut: Taking Control of Your Weight, Your Mood, and Your Long-term
Health. "The big message is we in the Western world have lost the diversity in our microbiota. We have to study these groups to figure out what we lost, what these microbes do, and how we get back to a healthy microbiota."
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