Itzagoal365.com – In recent years, scientists have made fascinating discoveries that suggest variations in the gut microbiome – the collection of bacteria and other microbes in our digestive system – may play a harmful role in promoting the development of diabetes and other diseases. What researchers at Harvard Medical School and the Joslin Diabetes Center have now found are dramatic differences between the gut microbiomes of ancient North American peoples and modern microbiomes, providing further clues to how these microbes may have evolved with changing diets.
To do the study, the scientists analyzed microbial DNA found in paleo feces (desiccated excrement) of indigenous people from unusually dry caves in Utah and northern Mexico. Published May 12 in the journal Nature, the work is believed to be the most thorough genomic analysis of ancient human gut microbiomes to date and the first to reveal never-before-identified microbial species from the samples, said the study’s lead author, Aleksandar Kostic, assistant professor of microbiology at Harvard Medical School and an assistant physician at the Joslin Diabetes Center.
Investigating the role of gut bacteria in disease and health has been the focus of Kostic’s ongoing efforts. In previous studies of children in Finland and Russia, Kostic and his colleagues showed that children in industrialized regions, who were much more likely to develop type 1 diabetes than children in non-industrialized areas, also had very different gut microbiomes.
“We were able to identify specific microbes and microbial products that we believe hinder good immune education in early life,” Kostic said. “And that leads to a higher incidence of not only type 1 diabetes later on, but other autoimmune and allergic diseases.”
The loss of gut microbiome diversity in industrial populations is thought to play a role in the development of chronic diseases, underscoring the importance of studying our ancestral gut microbiome, Kostic said. However, relatively little is known about the composition of the pre-industrial gut microbiome.
What, then, would a healthy human microbiome look like before the effects of industrialization?
“I’m convinced that you can’t answer that question with any modern living human,” Kostic said.
Insights from the ancient gut
Steven LeBlanc, an archaeologist formerly with Harvard’s Peabody Museum of Archaeology and Ethnology, came to Kostic with a possible solution: microbial DNA found in human paleo fecal samples collected by museums in arid environments in the North American Southwest.
Kostic and graduate student Marsha Wibowo took on the challenge and ended up comparing DNA from eight exceptionally well-preserved ancient gut samples from dry caves, some of which dated to the first century, with DNA from 789 modern samples.
Slightly more than half of the modern samples came from people known to have consumed industrialized and “Western” diets, while the rest came from people who consumed non-industrialized foods grown primarily in their own communities.
The differences between the microbiome populations were striking
For example, a bacterium known as Treponema succinifaciens “is not in a single Western microbiome that we analyzed, but it is in every single one of the eight ancient microbiomes,” Kostic said.
The ancient microbiomes matched better with the modern microbiomes of people who do not eat an industrial diet.
Remarkably, Wibowo found that nearly 40 percent of the ancient microbiome species had never been seen before. What could explain this high genetic variability? One possible explanation, the researchers hypothesized, could be diet.
“In ancient cultures, people ate a diverse range of foods, which allowed for the growth and presence of a more eclectic collection of microbes,” Kostic explained. “However, as people progressed toward industrialization and a more grocery-store diet, they lost a significant amount of nutrients that contribute to a more diverse microbiome.”
Additionally, the ancient microbiomes had a greater number of transposases than modern industrial microbiomes. Transposases are DNA sequences that can change their position on the genome.
The findings shed light on an unresolved scientific question: Do populations of human gut microbes evolve vertically or predominantly in response to their environment?
When the researchers examined the ancestry of the modern bacterium Methanobrevibacter smithii in ancient samples, they discovered that the organism evolved in accordance with a shared ancestral strain that has been dated to approximately the time when humans first crossed the Bering Strait into North America.
“Like our own genomes, these microbes appear to have traveled with us,” Kostic explained.
The research project started with the objective of identifying uncontaminated human paleofeces samples in unusually good condition.
“When we reconstructed these genomes, we exercised extreme caution,” Wibowo said. To verify the samples’ age and origin, the scientists used a technique called carbon-14 dating in conjunction with dietary tests and other techniques to ensure that the ancient samples were, in fact, human and not tainted by soil or other organisms, she explained. Additionally, the investigators verified that the selected samples exhibited the decay patterns that all DNA is known to exhibit over time.
“We believe this is a strategy used by microbes to adapt to a much more dynamic environment than the modern industrialized microbiome, where we eat the same foods and live the same lives year after year,” Kostic said. “By contrast, in a changing environment, microbes may use this much larger collection of transposases to seize and collect genes that will aid in their adaptation to new environments.”
Additionally, ancient microbial species possessed fewer antibiotic resistance genes. Additionally, the ancient samples contained fewer genes that encode proteins that weaken the protective mucous layer of the intestine, a process that has been connected to a variety of diseases.
