Reaching into The Past: Lessons from The Ancient Oral and Gut Microbiome

Intestinal microbiome, medical concept

Our gut and oral microbiome can have a big impact on our day-to-day health, but how have these microbial communities evolved over time and what can research into the genetics of ancient samples tell us about the modern microbiome?

This is a key question addressed by two groups of researchers who have recently extracted microbial genetic information from ancient oral and fecal samples, something that has only recently become a possibility thanks to advances in metagenome-assembled genome technology.

One study, published in the journal PNAS and led by Christina Warinner, Ph.D., a professor at the Max Planck Institute for Human History in Jena and also at Harvard University, focused on the oral microbiome. It compared microbial DNA collected from more than 120 dental biofilms of humans and Neanderthals (up to 100,000 years old), as well as chimpanzees, gorillas, and howler monkeys.

Genetic analysis of ancient microbiome samples is a very new field and the research team were unsure of how successful their study would be.

“While previous smaller-scale studies showed dental calculus as a good environment for the preservation of ancient DNA, we were not expecting to find just how consistently we would find authentic DNA from so many samples – particularly not that it could preserve even as far back as 100,000 years,” James Fellows Yates, lead author on the PNAS paper and Ph.D. student in Warinner’s lab, told Clinical Omics.

The research team found that the oral microbiome seemed to be surprisingly well preserved with at least ten groups of bacteria found in humans, Neanderthals and their closest primate relatives. Some of these bacteria are already known and are thought to help the gums and teeth to stay healthy, but there is very little known about some of the species they uncovered.

“The cool thing about the core genera we found were that most contain species that are known to play fundamental roles in the formation of the plaque biofilm: attachment to the enamel surface, ‘bridging’ taxa that allow other species to aggregate with the biofilm, and finally later colonizers,” says Fellows Yates.

“Importantly, however we identified quite a few taxa also considered ‘core’, yet we know very little about them—they don’t even have official names yet. [It’s] important to investigate what role these taxa may play in maintaining a health oral microbiome.”

As might be expected, the human and Neanderthal oral microbiome samples were more similar to each other than to more distantly related primates. There were more bacterial similarities seen in older (Ice Age) samples, perhaps suggesting human-Neanderthal couples and shared child rearing, but this was not seen in human samples that were 14,000 years old or less.

An interesting finding by the group was the presence of a subgroup of Streptococcus bacteria that are adapted to consume starch. Finding these bacteria in such old samples suggests that starchy foods had already become important in human diets before the introduction of farming and the evolution of modern humans.

“Reconstructing what was on the menu for our most ancient ancestors is a difficult challenge, but our oral bacteria may hold important clues for understanding the early dietary shifts that have made us uniquely human,” said Warriner. “Bacterial genomes evolve much more quickly than the human genome, making our microbiome a particularly sensitive indicator of major events in our distant and recent evolutionary past.”

The second project, published in Nature and led by Aleksandar Kostic, Ph.D., an assistant professor at Harvard Medical School and an investigator at the Joslin Diabetes Center.

Kostic and team sampled eight ancient human fecal samples found in the U.S. and Mexico (1000-2000 years old) and reconstructed the microbial genomes found in the samples using metagenome-assembled genome methods. They then compared them to modern human samples from both industrialized countries such as the U.S. and also to samples from non-industrialized communities.

Overall, 498 microbial genomes were reconstructed from the samples, 181 of which were predicted to be ancient and from the gut. Around 40% of these were not previously known species.

The researchers also analyzed 789 present-day human gut microbiome samples from eight countries. Of these, 418 were from industrialized countries including the U.S., Denmark and Spain, and 371 were from a publicly available database including gut metagenomes from people living in non-industrialized countries and communities including Fiji, Peru, Madagascar and Tanzania.

When the ancient and modern microbiome samples were compared there were more similarities than the researchers expected.

“We were afraid that that these samples would look like nothing else so that when we compared it to the modern microbiomes, we wouldn’t be able to tell whether there was some technical problem with them or whether they were just really so different. But surprisingly they cluster very well with non-industrial communities,” Kostic told Clinical Omics.

A more detailed analysis of the samples and species found also brough up some interesting findings. It is known that some aspects of modern life, particularly in industrialized communities have had negative effects on the gut microbiome of modern humans. For example, widespread antibiotic use and sanitation advances have both reduced infectious disease spread, but have unfortunately led to many beneficial species being wiped out.

Kostic explained that the current research tends to support these earlier observations. For example, antibiotic resistance markers were seen in many industrialized samples, a few non-industrialized samples and almost no ancient samples from the study.

He also cited the example of the mucin loving bacteria Akkermansia mucinophila, which was absent in the ancient samples, rare in the non-industrialized samples and common in industrialized samples.

“When it degrades mucus that this can cause problems. It gives other microbes in the gut direct access to the epithelium, which is normally protected by the mucus layer in the gut, and it can promote inflammation,” says Kostic.

“That’s one of the, the ways that we see this phenomenon of increased barrier permeability, also known as leaky gut.”

Evidence from this study and others also suggests that ancient and non-industrialized people had a higher diversity of carbohydrate utilizing microbes in their gut producing beneficial metabolites than industrialized samples. Researchers also think the increased level of regular exercise undergone by ancient people and those living in non-industrialized communities today may also have a beneficial effect on the microbiome.

“We know that certain chronic diseases have been increasing dramatically in the Western world in recent decades, and there is a much lower incidence of these diseases in non-industrial communities. We presume that there was also a low incidence of chronic disease in the ancient populations that we studied,” says Kostic.

“An important concept emerging from our work is that if the theory of the ‘disappearing human microbiome’ is correct, then in order to lower the burden of chronic diseases simply eating right and exercising is not enough — we need to somehow “re-seed” the modern human microbiome with the species that we have lost.”

Stephanie Schnorr, Ph.D., is a researcher at the University of Nevada, Las Vegas who was not directly involved with the two studies discussed here. Her research has a focus on the human diet and the gut microbiome in modern and ancient samples.

“These results can inform about our connections, either ecologically or phylogenetically, with near and distant primate relatives, as well as our context in nature as mammals, and as omnivores, but with the very special circumstance that we heavily modify our food and environments using culture and technology,” she says.

“I also think it’s important to learn from looking back in time at how ancient human associated communities compare to those of today, in terms of diversity, gene traits, and indications of association with our physiology in order to understand how these have changed over time and through what means or due to what kinds of stimuli or disturbances.”

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