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Microbial Genes Characterized in Human Gut, Oral Microbiomes

NEW YORK – A team from the US and Canada has started documenting and characterizing the collection of microbial genes swimming around in the human mouth and gut — results reported online today in Cell Host & Microbe.

"[W]e hope that our catalog, along with a searchable web application, will have many practical uses and seed many directions of research in the field of host-microbe relationships," co-senior and co-corresponding author Chirag Patel, a biomedical informatics researcher at Harvard Medical School, said in a statement.

Patel and his colleagues brought together meta-genomic sequence data for almost 3,700 mouth and gut samples collected for more than a dozen prior studies, narrowing in on nearly 45.7 million non-redundant microbial genes. Half of the microbial genes appeared to be so-called singletons, present in just one of the samples included in the analysis, including genes spanning a wide range of functional pathways.

Although prior studies have tallied the bacterial strains and species present at sites within and across the human body, Patel noted that "[t]wo members of the same bacterial strain could have markedly different genetic makeup, so information about bacterial species alone could mask critical differences that arise from genetic variation."

To dig into the bacterial genes present in the human mouth and gut, the researchers did de novo assembly on 3,655 publicly available metagenomes previously generated from 1,473 human mouth samples and 2,182 gut samples, uncovering nearly 24 million microbial genes in the mouth microbiome, along with more than 22 million gut microbiome-related genes. They noted that 549,610 genes turned up in both the oral and gut microbiomes.

The team's analysis suggested that the set of shared, non-singleton sequences found in at least three samples often came from genes in pathways found in oral and gut microbiomes. On the other hand, singleton genes found exclusively in just one of the microbiomes appeared to be more genetically diverse, springing from a wide range of functional pathways.

"If a microbe needs to become resistant to an antibiotic because of exposure to drugs or suddenly faces a new selective pressure, the singleton genes may be the wellspring of genetic diversity the microbe can pull from to adapt," first author Braden Tierney, a graduate student affiliated with the Joslin Diabetes Center and Harvard Medical School, said in a statement.

Along with the singleton and non-singleton gene analyses, the team put together an online database outlining the microbial genes detected in the context of the wider mouth and gut microbiomes.

"We built this resource with a focus on the variation of genomic content across the human microbiome, identifying an order of magnitude more genes in both the oral and gut microbiomes than ever before," the authors reported.