Scientists are rapidly gathering evidence that variants of the gut microbiomes, collections of bacteria and other microbes in our digestive system, can play a harmful role in diabetes and other diseases. Today, scientists at the Joslin Diabetes Center have discovered dramatic differences between the gut microbiomes of ancient North American peoples and modern microbiomes, providing new evidence on how these microbes can evolve with different diets.
Scientists analyzed microbial DNA found in native human paleofeces (desiccated droppings) from abnormally dry caves in Utah and northern Mexico with extremely high levels of genomic sequencing, says Joslin’s assistant researcher Aleksandar Kostic, PhD, main author of a Nature paper presenting the work.
By performing a broader and more in-depth genomic analysis than previous studies of ancient human gut microbiomes, the study was the first to reveal new species of microbes in specimens, says Kostic, who is also an assistant professor of microbiology at Harvard Medical School.
In previous studies of children in Finland and Russia, Kostic and his colleagues showed that children in industrialized areas, who were much more likely to develop type 1 diabetes than those in non-industrialized areas, also had gut microbiomes. very different. “We were able to identify specific microbes and microbial products that we believe hindered proper immune education early in life,” Kostic explains. “And that later leads to higher incidents of not only type 1 diabetes, but other autoimmune and allergic diseases.”
So what would a healthy human microbiome look like before the effects of industrialization? “I am convinced that you cannot answer this question with any living modern people,” says Kostic, who points out that even tribes in extremely remote areas of the Amazon are contracting Covid-19.
Steven LeBlanc, an archaeologist formerly of the Peabody Museum of Archeology and Ethnology at Harvard, came to Kostic with a dramatic alternative source: microbial DNA found in human paleofecial samples that museums have collected in arid southwestern environments. from North America.
Kostic and graduate student Marsha Wibowo rose to the challenge, ultimately comparing DNA from eight exceptionally well-preserved ancient gut samples from dry caves (some dating from the first century AD) with DNA from 789. modern samples. Just over half of modern samples were from people on an industrialized “Western” diet and the rest from people consuming non-industrialized foods (grown mostly in their own communities).
The differences between the microbiome populations were striking. For example, a bacterium known as Treponema succinifaciens “is not found in just one western microbiome that we analyzed, but in each of the eight ancient microbiomes,” says Kostic. Ancient microbiomes corresponded more closely to modern non-industrial microbiomes.
Surprisingly, Wibowo found that almost 40% of ancient microbial species had never been seen before. What could explain this strong genetic variability?
“In ancient cultures, the foods you eat are very diverse and can support a more eclectic collection of microbes,” Kostic speculates. “But as you move towards industrialization and more into a grocery store diet, you lose a lot of nutrients that help support a more diverse microbiome.”
Ancient microbiomes also had relatively higher numbers than modern industrial microbiomes of transposases (transposable pieces of DNA sequences that can change locations in the genome).
“We think this could be a strategy for microbes to adapt in an environment that changes a lot more than the modern industrialized microbiome, where we eat the same things and live the same life more or less all year round,” says Kostic. “As in a more traditional environment things change and microbes have to adapt. They could use this much larger collection of transposases to grab and collect genes that will help them adapt to different environments.”
In addition, ancient microbial populations incorporated fewer genes linked to antibiotic resistance. The older samples also had a lower number of genes that produce proteins that break down the intestinal mucus layer, which can then produce inflammation linked to various diseases.
Additionally, the work may shed light on scientific controversy over whether populations of gut microbes are transmitted vertically from generation to generation of humans, or primarily evolve from surrounding environments.
By examining the lineage of the common bacterium Methanobrevibacter smithii in ancient samples, they found that its evolution was consistent with a common ancestral strain dated to around the time when humans first migrated through the Bering Strait in North America. “These microbes, just like our own genomes, travel with us,” says Kostic.
The research project began with the need to identify uncontaminated human paleofeces samples that were kept in exceptionally good condition. “When we reconstructed these genomes, we tried to be very conservative,” says Wibowo.
In addition to carbon-14 dating, the scientists used dietary analyzes and other methods to validate that the selected samples were indeed human and not contaminated by soil or other animals such as dogs, she says. . Investigators also confirmed that the chosen samples exhibited the decay patterns that all DNA is known to exhibit over time.
The team performed much deeper DNA sequencing than had been done in previous efforts, at least 100 million reads, with 400 million DNA reads for a specimen.
A collaborator, anthropologist Meradeth Snow, PhD, of the University of Montana at Missoula, led an initiative to seek perspectives on the work of Native American communities in the southwest region. “We recognize and appreciate the individuals whose genetics and microbes were analyzed for this research, as well as today’s individuals with associated genetic or cultural heritage,” the study said.
The researchers plan to expand their studies to many more specimens of ancient microbiomes, with the aim of detecting new microbial species and trying to predict their metabolic functions. Kostic is intrigued by the possibility of resuscitating these ancient microbes in the laboratory, inserting ancient genomes into the closest living bacterial species. “If we can grow them in the lab, we can better understand the physiology of these microbes,” he says.
LeBlanc helped Joslin’s investigators bring together collaborators, possibly recruited from a dozen establishments. Among the key contributions, Dr Snow of Montana led the extraction and preparation of ancient DNA, and Christina Warinner, PhD at Harvard, offered her expertise on the ancient human microbiome. “It was amazing to learn from all these brilliant collaborators,” says Wibowo. “You really need a village.”