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Researchers Reconstruct Ancient Human Gut Microbiomes From Paleofeces

NEW YORK — The ancestral human gut microbiome is broadly similar to those of modern-day individuals from non-industrialized populations, a new analysis has found. But more than a third of the reconstruction microbial genomes were novel.

The gut microbiomes of modern-day individuals from industrialized populations are marked by a loss of genetic diversity. This loss has been tied to chronic conditions like obesity and autoimmune disease. Having a better understanding of ancestral human gut microbiomes could provide greater insight into how the gut microbiome has changed with industrialization.

Harvard Medical School's Aleksandar Kostic and his colleagues reconstructed ancient microbial genomes using a set of eight paleofeces between 1,000 years and 2,000 years old uncovered in the southwestern US and Mexico. As they reported on Wednesday in the journal Nature, they compared these ancient gut microbes to modern-day samples from both industrialized and non-industrialized populations.

Kostic noted they weren't sure going into their analysis whether the ancient microbiomes would cluster off by themselves or be similar to either of the modern-day microbiomes. "I was excited by this result because it supported the idea that high-quality ancient human microbiomes could be reconstructed," he said in an email. "And also it made intuitive sense because it might be fair to assume that the lifestyle of these ancient people was much more similar to modern people living in non-industrialized communities relative to industrialized communities."

For their analysis, the researchers performed shotgun metagenomic sequencing on 15 paleofeces samples, though seven were excluded due to poor assembly, contamination, or being from a non-human source. They additionally analyzed 789 stool samples from present-day individuals from both industrialized and non-industrialized populations spanning eight countries for comparison.

The taxonomic makeup of the paleofeces was more similar to the non-industrialized versus the industrialized present-day samples, according to an analysis using the computational tool MetaPhlAn2. There were further no significant differences in the phyla present between the paleofeces and the non-industrialized samples, though a number of phyla differed between them and industrialized samples. For instance, Bacteroidetes and Verrucomicrobia were enriched in the industrial samples, while Firmicutes, Proteobacteria and Spirochaetes were less abundant, as compared to the paleofeces.

However, as this analysis relied on taxa being present in the MetaPhlAn2 database, the researchers also embarked on de novo genome reconstruction of the paleofeces samples and the modern-day samples from Mexico. In all, they reconstructed 181 gut microbe genomes from the paleofeces samples. Of these, 39 percent were novel microbial species and 11 percent belonged to novel genera.

A functional analysis further uncovered differences between the paleofeces and modern-day gut microbiome samples. Both modern-day gut microbiome samples from industrialized and non-industrialized populations were enriched for antibiotic resistance genes, as compared to the ancient samples. Additionally, the paleofeces and the modern-day samples from non-industrialized populations were enriched for carbohydrate-active enzymes, or CAZymes, as compared to industrialized population microbiomes. The ancient samples were particularly enriched for chitin-degrading CAZymes, possibly reflecting an ancient diet that included chitin.

While these differences in gut microbiome makeup could be driven by changes in human diet over time, they also could in part be attributed to changes in living conditions like the advent of antibiotics and increased sanitation and changes in physical activity levels that come with industrialization, Kostic added.

He and his colleagues plan to reconstruct additional gut microbiomes from other regions of the world and other time frames to, in part, piece together whether the novel microbes they identified here were present elsewhere and what may have happened to them. Further afield, they hope to someday test whether fecal microbiota transplants from non-industrial samples similar to these ancient samples could help treat chronic diseases.

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