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Articles Highlight Advances, Potential Applications of Gut Microbiome Research

NEW YORK (GenomeWeb News) – A collection of studies, perspectives articles, and reviews in this week's issues of Science and Science Translational Medicine outline the progress that's been made in understanding the gut microbiome since researchers started systematically studying it with high-throughput sequencing and related approaches.

Following from a special issue on the gut published in Science in 2005, the publications include historical perspectives on studies of microbes in the gut, issues related to gut microbiome studies, both for researchers and society as a whole, findings from the field, and theoretical frameworks for interpreting gut microbiome data.

Areas of interest for future study are also highlighted, as researchers continue to delve into gut microbiome contributions to health, disease, and immune function and consider the possibility of using therapeutics to tailor or augment this internal community.

Among the new research presented in the package is work by a University of Pennsylvania-led team looking at how the function of a group of human immune cells known as innate lymphoid cells influence the location of beneficial gut bacteria.

That team's mouse studies indicated that depriving mammals of these intestinal immune cells allows normally helpful bugs — in this case bacteria from the Alcaligenes genus — to stray from their home in the gut and move to other parts of the body, where they can cause systemic inflammation.

"A fundamental question that has puzzled researchers for many years is how did the human body evolve to accommodate all these commensal bacteria and keep them in their correct locations?" senior author David Artis, a University of Pennsylvania microbiology and pathobiology researcher, said in a statement.

"The indication from these studies is that the body may have different pathways to limit the spread of commensal bacteria," he added, "and these pathways may be tailored to specific types of bacteria."

Another study looked at virulence factors and their role in interactions between commensal microbes and potential pathogens, while a third, by researchers from Cedars-Sinai Medical Center, the University of California at Los Angeles, and the University of Aberdeen, explored other sorts of host immune system interactions with the gut microbiome.

Authors of the latter study used Roche 454 and Illumina GAII sequencing of fungal ribosomal DNA in mouse fecal samples to characterize fungal communities in the mouse gut, identifying more than 100 known fungal species, along with as many uncharacterized fungi.

In the absence of an innate immune receptor known as Dectin-1, though, the team found that mice no longer interacted the same way with these fungi. Instead, their gut microbe communities housed higher-than-usual levels of fungi that act as opportunistic pathogens.

Moreover, researchers reported, mice lacking Dectin-1 were more prone to inflammation when exposed to dextran sodium sulfate, a chemical that induces colitis.

Consistent with the notion that altered interactions with the gut mycobiome might affect inflammatory bowel disease severity in humans as well, that research team went on to identify a variant in the gene coding for the human version of Dectin-1 that is associated with forms of ulcerative colitis that respond poorly to treatment.

"This study takes us an important step closer to understanding how fungi contribute to disease, as well as significantly expanding our understanding of what types of fungi are living in our bodies," Cedars-Sinai researcher Iliyan Iliev, the study's first author, said in a statement.

Interactions between the host immune system and members of microbial communities in the gut were also explored in two accompanying reviews in Science and in Science Translational Medicine. In other reviews, meanwhile, researchers explored the possibility of using ecological theory to explore gut community dynamics and related therapeutics.

While some contributors to the collection focused on strategies for understanding and applying microbial functions not only for human health but also in industrial settings, still others focused on relationships between gut microbes, nutrition, and metabolism — interactions that have some considering the prospect of therapeutics that target the metagenome.

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