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Mouse Study Suggests Host Genetics Influence Core Gut Microbiome

By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – Host genetics help shape the type and abundance of microbes living in the mouse gut, according to a paper appearing in the early, online version of Proceedings of the National Academy of Sciences last night.

Researchers from the University of North Carolina and the University of Nebraska used pyrosequencing to assess gut microbial communities in hundreds of mice. Although they found a core group of microbes in the guts of most of the mice tested, they explained, the team also detected differences in the abundance of core microbiome players from one animal to the next — with host genetics apparently influencing at least some of this variation.

"These data provide clear evidence for the importance of host genetic control in shaping individual microbiome diversity in mammals, a key step toward understanding the factors that govern the assemblages of gut microbiota associated with complex diseases," senior author Daniel Pomp, a genome science and nutrition researcher at the University of North Carolina, and co-authors wrote.

Pomp and his co-workers used the Roche 454 GS FLX Titanium approach to sequence the V1-V2 region of microbial 16S rRNA genes from 645 mouse fecal samples.

When they took stock of the microbes present in all of these samples, the researchers found microbes from more than 400 genera, representing 16 phyla and two-dozen bacterial classes.

Of these, microbes from just 64 microbial taxonomic groups and 19 genera seem to be shared between most of the mice tested. And the abundance of microbes in this group of so-called "core measurable microbiota" or CMM varied from one animal to the next, the team explained.

When they added in host genetic data, looking at how genotype at 530 host SNPs related to core microbiome characteristics, the researchers identified 13 quantitative trait loci associated with core gut microbiome characteristics, along with another five that potentially influence the CMM.

But not all of the QTLs have the same sorts of influence over gut microbe population structure, they explained, noting that "some loci control individual microbial species, some control groups of related taxa, and some have putative pleiotropic effects on groups of distantly related organisms."

For example, the researchers pinned down QTLs specifically tied to microbes that are closely related to one another, as well as QTLs that simultaneously influence the abundance of microbes from different phyla.

Based on their findings so far, the researchers argue that the core gut microbiome in mice is influenced by host genetics in such a way that components of this community are passed along as a polygenic trait from one mouse generation to the next.

"Our discovery that the CMM taxa, which are some of the most abundant organisms in the [gastrointestinal tract], are subject to host genetic control now supports the concept of a core microbiome as a universal feature among vertebrate hosts, with the relative abundance of CMM taxa collectively behaving as a complex polygenic trait," the team explained.

While they noted that more research is needed to determine how mouse genetics affect the gut microbiome — and to determine the extent to which host genetics influence gut microbial communities in humans and other animals — those involved in the study say their findings pave the way for a more complete understanding of the gut microbiome.

"Establishment of this murine model and demonstration of heritability are important steps toward experimental paradigms that can define the mechanisms which drive the assembly of the microbiota in individuals," Pomp and colleagues wrote. "We believe that, with highly refined data from murine models, mapping heritable genetic factors controlling gut microbiome composition will ultimately be an important tool for studying disease."

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