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Deep in the human gut, myriad “good” bacteria and other microbes help us digest our food, as well as keep us healthy by affecting our immune, metabolic, and nervous systems. Some of these humble microbial assistants have been in our guts since before humans became human—certain gut microbes are found in almost all primates, suggesting they first colonized a common ancestor. But humans have also lost many of these helpers found in other primates and may be losing even more as people around the world continue to flock to cities, a researcher reported last week at a microbiology meeting in Washington, D.C. Those absent gut microbes could affect human health, he says.

“This work helps us develop a new understanding of the course of human biological and cultural development,” says Lev Tsypin, a microbiology graduate student at the California Institute of Technology who was not involved in the new study.

The microbiome comprises all the bacteria, fungi, viruses, and other microscopic life that inhabit an individual, be it a person, a plant, or a planaria. For humans and many other species, the best characterized microbiome centers on the bacteria in the gut. The more microbiologists study these gut microbes, the more they link the bacteria to functions of their hosts. In humans, for example, gut bacteria influence how the immune system responds to pathogens and allergens, or interact with the brain, affecting mood.

Andrew Moeller, an evolutionary biologist at Cornell University, was one of the first to show that gut bacteria and humans have built these relationships over a very long time. Six years ago, he and colleagues reported the work showing human gut microbes are very similar to those in other primates, suggesting their intestinal presence predates the evolution of humans.

But his follow-up studies, and work by others, also indicate the human gut microbiome has, in a general sense, become less diverse than the gut microbes in our current primate cousins. One study found 85 microbial genera, such as Bacteroides and Bifidobacterium, in the guts of wild apes, but just 55 in people in U.S. cities. Splitting the difference, people in less developed parts of the world have between 60 and 65 of those bacterial groups, an observation that ties the decrease in microbial diversity to urbanization.

Changes in diet as humans moved on from their hunter-gatherer past and then into cities, antibiotic use, more life stresses, and better hygiene are all possible contributors to the loss of human gut microbes, says Reshmi Upreti, a microbiologist at the University of Washington, Bothell. Several prominent researchers have argued that this lower diversity could contribute to increases in asthma and other inflammatory diseases.

In their past work comparing primate gut microbiomes, Moeller and colleagues simply looked at genetic markers that broadly identified what genera of bacteria or other microbes were present. Moeller has now taken a closer look at exactly what microbial species have gone missing from the human gut by trying to compile the full genomes of current gut microbes in our closest relatives. “You can tell what went extinct [in humans] by looking at what’s in other primates,” Moeller says.

Moeller and his colleagues collected dung from several groups of African chimps and bonobos, isolating and sequencing microbial DNA in the feces that derives from the gut’s microbes. They also gathered gut microbe DNA data previously collected for gorillas and other primates by other researchers—accumulating details on 22 nonhuman primates. With computers, they were able to compile the fragments of DNA sequenced into whole genomes of the gut microbes present. By comparing these data, gut microbiome data from 49 human populations and ancient DNA from fossilized human poop, and overlaying it all on the primate family tree, the team could depict the changing relationships among the different microbial groups across various primates.

They showed some specific gut microbes diversified as they evolved with their primate host, whereas others went missing. Quite a few microbes have abandoned the human gut, as humans have lost 57 of the 100 or so branches, or clades, of microbes currently found in chimps or bonobos and at least one other nonhuman primate, Moeller reported on 11 June at Microbe 2022, the annual meeting of the American Society for Microbiology. Moeller was also able to estimate when some of the human gut microbes disappeared. A few were lost thousands of years ago, and some have disappeared more recently, with city dwellers having lost the most, Moeller reported.

“What impressed me was how simple yet insightful the approach he developed was,” says Jessica Maccaro, an evolutionary biology graduate student at the University of California (UC), Riverside.

It is always challenging to prove a gut microbe has been lost from a host, Tsypin notes, as microbes that are rare in the gut might not make it into feces and therefore might be missed in these kinds of studies. And Moeller agrees he needs to look at more human populations to be sure the microbes are not hiding out in guts of people in distant parts of the world. Already, efforts are underway to collect and preserve microbiomes from people who live far away from cities in case they have these missing microbes.

Kyle Meyer, a microbiologist at UC Berkeley, argues such losses are not necessarily a problem. “Maybe we don’t need them,” he points out. But Moeller is worried. “We are really doing some scary stuff to our microbiomes,” he warns.

Moeller and others also suggest identifying the missing microbes may be the first step toward bringing them back. “If we determine that these groups were providing important functions to keep humans healthy,” Maccaro says, “perhaps we can restore them with probiotics.”

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