Medical Interventions Rapidly Change Isolated Indigenous Microbiomes

Amerindian communities across southern Venezuela have remained isolated from Western medicine. Villages are often only accessible by river or air, and villagers rely on hunting and fishing for food. This isolation has a cost: These communities are among the last in the Americas to be affected by onchocerciasis, also known as river blindness. A parasite transmitted by black flies causes this condition, which can be treated by mass administration of the antiparasitic drug ivermectin. The Carter Center’s Onchocerciasis Elimination Program for the Americas (OEPA) has been delivering the drug across the Americas since 1993.

Now, an international research team has suggested that OEPA’s program may have had an unexpected impact by changing the microbiome of these isolated communities. Analysis of the microbiota living in and on the villagers showed that their diverse bacterial communities became more restricted and more alike to those seen in urban populations after just a handful of medical visits. The researchers say the findings, which were published in Cell Reports, offer a unique perspective on how easily the human microbiota can change.

What Changes the Microbiome?

The OEPA program started operating in southern Venezuela in late 2015. The team brought basic medical care and antiparasitic drugs like ivermectin to the communities. “The program offered a rare natural experiment,” said Maria G. Dominguez-Bello, a microbiologist at Rutgers University and coauthor of the new study, in a statement. “We know from studies in urban societies that antibiotics can have huge impacts on gut microbes,” she said. “But we didn’t know how even basic medicine might affect people with very limited exposure to medicine.”

Researchers from Dominguez-Bello’s group visited seven villages alongside the OEPA team in October 2015, before the medical program began, and again in February 2016.

While previous studies have shown the combined impact of dietary and lifestyle changes on the microbiota, it has been difficult to disentangle these effects. The two sampling dates fell within the same dry season, meaning the villagers’ food supply would have varied little between the visits, allowing the researchers to focus more clearly on the effect of the medical program alone on the villagers. They collected over 1,500 samples from 335 participants, including fecal samples and swabs of the skin, nose, and mouth.

Reduced Microbiome Diversity

The first round of sampling showed that the villagers had highly diverse gut bacterial populations, significantly more diverse than those of villagers in Amazonian communities with more regular contact with urban populations. Their guts included species such as Prevotella and Treponema, which are linked to better fiber digestion. Four months later, the remote communities’ bacterial populations were now more similar to those of the higher-contact villagers. Prevotella and Treponema had declined, replaced with higher levels of Bacteroidota and Verrucomicrobia—groups more common in urban populations. These shifts were more pronounced in children.

Microbes in the villagers’ guts also underwent functional changes. Genetic analysis showed that microbial genes linked to fiber fermentation and some metabolic processes became rarer, while genes linked to simple carbohydrate metabolism and antimicrobial resistance increased.

The changes were not all uniform. While diversity in the mouth and skin microbiota also decreased after medical contact, nasal microbiota diversity actually increased. The researchers were unable to explain the directional differences in these shifts. Because the researchers only visited the villages once after the medication administration, they were also unable to assess long-term changes in the villagers’ microbiomes.

Microbial and Medication Lessons for the Future

The team says that medical programs like OEPA, while saving lives, should consider ways of mitigating a medication’s impact on the microbiome. “There is still a big difference between the microbiome of these communities and the average person in the United States. But if diversity continues to decline, there could be risks of losing important functions,” said Dominguez-Bello.

“Many conditions, from obesity to allergies and even some cancers, are linked to gut microbes. Understanding how to protect and restore microbial diversity could become an important part of improving our health,” she concluded.