Thursday 20 May 2021

Ancient gut microbiomes may offer clues to modern diseases


Scientists are rapidly gathering evidence that variants of gut microbiomes, the collections of bacteria and other microbes in our digestive systems, may play harmful roles in diabetes and other diseases. Researchers have found dramatic differences between gut microbiomes from ancient North American peoples and modern microbiomes, offering new evidence on how these microbes may evolve with different diets.


The scientists analyzed microbial DNA found in indigenous human paleofeces (desiccated excrement) from unusually dry caves in Utah and northern Mexico with extremely high levels of genomic sequencing.


Performing genomic analysis more broadly and deeply than previous studies on ancient human gut microbiomes, the study was the first to reveal novel species of microbes in the specimens,.


The scientists compared the DNA from eight exceptionally well-preserved ancient gut samples from dry caves (some dated as early as the first century of the current era) with DNA in 789 modern samples. Slightly more than half of the modern samples were from people on industrialized "Western" diets and the remainder from people consuming non-industrialized foods (grown mostly within their own communities).


The differences between microbiome populations were striking. For instance, a bacteria known as Treponema succinifaciens is not in a single Western microbiome analyzed, but it's in every single one of the eight ancient microbiomes. The ancient microbiomes did match up more closely with modern non-industry microbiomes.


Strikingly, the researchers found that almost 40% of the ancient microbial species had never been seen before. What might explain this high genetic variability?


In ancient cultures, the foods you're eating are very diverse and can support a more eclectic collection of microbes. But as you move toward industrialization and more of a grocery-store diet, you lose a lot of nutrients that help to support a more diverse microbiome.


The ancient microbiomes also had relatively higher numbers than the modern industrial microbiomes of transposases (transposable elements of DNA sequences that can change location in the genome).


This could be a strategy for the microbes to adapt in an environment that shifts a lot more than the modern industrialized microbiome, where we eat the same things and live the same life more or less year-round. Whereas in a more traditional environment, things change and microbes need to adapt. They might use this much larger collection of transposases to grab and collect genes that will help them adapt to the different environments.


Moreover, the ancient microbial populations incorporated fewer genes related to antibiotic resistance. The ancient samples also featured lower numbers of genes that produce proteins that degrade the intestinal mucus layer, which then can produce inflammation that is linked with various diseases.


Additionally, the work may shed light on a scientific controversy about whether populations of gut microbes are transmitted vertically from generation to generation of humans, or evolve primarily from surrounding environments.


Looking at the lineage of the common bacteria Methanobrevibacter smithii in the ancient samples, they found its evolution was consistent with a shared ancestral strain that has been dated to roughly when humans first migrated across the Bering Strait into North America.


In addition to carbon-14 dating, the scientists used dietary analyses and other methods to validate that the selected samples were indeed human and not contaminated by soil or by other animals such as dogs, she says. The investigators also confirmed that the chosen samples displayed the patterns of decay that all DNA is known to exhibit over time.


The team performed far deeper sequencing of DNA than what was achieved in previous efforts, at least 100 million reads, with 400 million reads of DNA for one specimen.


The researchers plan to expand their studies to many other ancient microbiome specimens, aiming to detect novel microbial species and trying to predict their metabolic functions.




Marsha C. Wibowo, Zhen Yang, Maxime Borry, Alexander Hübner, Kun D. Huang, Braden T. Tierney, Samuel Zimmerman, Francisco Barajas-Olmos, Cecilia Contreras-Cubas, Humberto García-Ortiz, Angélica Martínez-Hernández, Jacob M. Luber, Philipp Kirstahler, Tre Blohm, Francis E. Smiley, Richard Arnold, Sonia A. Ballal, Sünje Johanna Pamp, Julia Russ, Frank Maixner, Omar Rota-Stabelli, Nicola Segata, Karl Reinhard, Lorena Orozco, Christina Warinner, Meradeth Snow, Steven LeBlanc, Aleksandar D. Kostic. Reconstruction of ancient microbial genomes from the human gut. Nature, 2021; DOI: 10.1038/s41586-021-03532-0


Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (

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