60% of shared microbes rare or absent in industrialized populations
Two Indigenous communities separated by roughly 7,000 miles — the Hadza of northern Tanzania and the Tsimane of the Bolivian Amazon — share about 1,200 species of gut bacteria, a near-90% overlap that researchers say traces back to a common microbial ancestor about 17,000 years ago, before ancestral human populations crossed the land bridge that once connected Russia and Alaska.
The finding, published in the journal Nature, comes from a team led by Justin Sonnenburg, a professor of microbiology and immunology at Stanford University and the study’s senior author. The researchers analyzed stool samples collected from dozens of individuals through the Tsimane Health and Life History Project and compared the genetic material with earlier analyses from the Hadza community. The study, which relied on stool samples from both groups, also showed that both the Hadza and Tsimane microbiomes were markedly different from city folk, even those living nearby.
Sonnenburg has previously contrasted the microbiomes of the Hadza with those of industrialized people. He and his colleagues wanted to compare these two Indigenous communities with one another. “They’re living a lifestyle that’s much more similar to the lifestyle our ancestors lived, and so therefore is more hospitable to microbes that were handed down through many generations over the course of human evolution,” Sonnenburg said.
Sonnenburg called the overlap “startling,” given the geographic separation and the communities’ distinct diets. In a typical gut microbiome, hundreds to thousands of species interact with each other — mostly bacteria, along with some fungi and viruses, he said. “The microbes are helping us digest foods in our gut, secreting molecules that get absorbed into the bloodstream,” Sonnenburg said. “And our blood, of course, circulates throughout our bodies.” The gut bacteria can influence moods, behavior, and the body’s response to infections, affecting fundamental parts of biology and health, he added. Microbiomes are dynamic — they can also change quickly, depending on what foods people eat and what medicines they take.
Using mutation-rate dating on the bacterial genomes, the team estimated that the shared strains diverged from a common ancestor roughly 17,000 years ago on average, with some lineages dating much further back. The timing tracks closely with the window during which ancestral human populations moved through Eurasia and into the Americas, Sonnenburg said. “Once the land bridge went away, we had a clear picture that it was going to be very hard for them to exchange gut bacteria through traditional human contact means,” said Ben Good, a theoretical biophysicist at Stanford and a study co-author. The team’s analysis was “consistent with the idea that these populations in South America, Africa and probably in other parts of the world are not just acquiring microbes from their environment that match their lifestyle, so much as transmitting microbes over generations,” Sonnenburg said.
Other researchers said the pattern supports a broader view of the gut microbiome as something that migrated alongside human populations and may have co-evolved with them over generations. “If we were inhabited by very similar microbes over a long period of time, it suggests that our human genomes may have come to expect a certain set of microbes and functions,” said Sonnenburg, the study’s senior author. “When you start to lose biodiversity in your gut, there may be big issues for your human biology to adjust to and accommodate.” “If the bacteria and the humans had a shared history for many, many generations, there are more opportunities for selection,” said Taichi Suzuki, an assistant professor at Arizona State University who studies microbiomes and was not affiliated with the study. “We would expect more potential dependencies between [the co-evolved] gut microbes and our own genome, basically.”
Around 60% of the bacterial species the Hadza and Tsimane share are rare or absent in people living modern, industrialized lives, according to the paper. “The microbes that inhabit my gut are very unlikely to be the microbes that were handed down through the generations from my great great grandparents,” Sonnenburg said. “They are much more likely to be a product of my current lifestyle and the people that I’ve interacted with locally.” Sonnenburg argued the observation raises questions about whether losing those ancestral lineages could be harming human health. While proving causation is tricky, “a lot of the arrows are pointing in the same direction, that our modern microbiome has changed in ways that may be propagating inflammation, may be unhealthy for us and leading to inflammatory diseases,” Sonnenburg said.
Andrew Moeller, an associate professor of evolutionary biology at Princeton University, said the alternative — that the industrialized gut microbiome reflects adaptation rather than loss — remained open. “Another alternative is that the industrialized microbiome profile may actually be adapted to an industrialized lifestyle,” Moeller said. “From a health perspective, is it good or deleterious that industrialized humans have lost a lot of ancestral microbial taxa? We actually don’t know.” Documenting what’s been kept and lost is a step towards figuring that out, Moeller said.
Humans typically acquire their first gut bacteria during birth, from their mother’s vaginal canal and skin, Suzuki said, and accumulate more through household and community contact. Transmission also occurs through the fecal-oral route — ingesting microscopic particles in air and dust. “Something that might make that less disgusting is realizing how tiny these things are,” Moeller said. “They’re a micron or less in length, and in principle, you just need one cell to found a new population.” The gut also picks up generalist microbes that exist in the environment by ingesting food, soil and water, Moeller said. E. coli, for instance, is a bacteria found in many places that thrives in the bodies of humans and many animals.
Some researchers hypothesize that the microbes that have co-evolved with humans may help protect human health — or at least do less harm, Suzuki said. In a case study, those with African ancestry have been found to have a far lower risk of getting seriously ill from an African strain of H. pylori, presumably because their genomes developed alongside the bacteria, compared with those of other ancestries who are susceptible to developing a deadly stomach cancer, Suzuki said. The pattern shows the potential harms of a mismatch between gut microbes and the human genome, Suzuki said.
Establishing cause and effect would require far more work. “With regards to the evolutionary questions like, which of [these] microbes have we co-evolved with? Which ones have we lost that would be beneficial to regain? It’s still early days for that line of questioning,” Moeller at Princeton said. Determining which gut bacteria have been with humans for a long time helps move the field forward, Moeller added — a step the Nature paper advances.