Nature, as Well as Nurture, Shapes Human Gut Microbiome

Lara C. Pullen, PhD

November 11, 2014

The composition of an individual's gut microbiome is influenced not just by environmental exposure but also by the genetics of the host. The resulting human gut microbiome affects host metabolism, thereby contributing to obesity.

Julia K. Goodrich, a graduate student at Cornell University in Ithaca, New York, and colleagues published their analysis of the TwinsUK population in the November 6 issue of Cell. They studied 416 twin pairs and sequenced the genome of microbes found in more than 1000 fecal samples.

They report that identical twins have gut microbiomes that are more similar than those of fraternal twins.

The investigators identified the relatively unknown family Christensenellaceae as the most highly heritable taxon in their data set. In contrast, the more well-known Bacteroidetes were not heritable, suggesting that environmental factors largely contribute to their role in the gut microbiome.

They found that the Christensenellaceae family is more common in the guts of individuals with low body weight. Moreover, when the investigators transplanted the specific microbes into mice, they found that they protected against weight gain.

The results are consistent with previous studies that have also suggested host genetic effects. The previous studies, however, have been underpowered to clearly identify the findings described by Goodrich and colleagues. Thus, the current article represents a shift in understanding of the role of genetic variation on the diversity of gut microbes.

The newly described association between the Christensenellaceae family and human genes raises questions about the nature of the interaction. Unfortunately, the study was not designed to identify human genetic factors that might be important in the relationship with this family of microbes.

"Host genetic variation drives phenotype variation, and this study solidifies the notion that our microbial phenotype is also influenced by our genetic state. We have shown that the host genetic effect varies across taxa and includes members of different phyla. The host alleles underlying the heritability of gut microbes, once identified, should allow us to understand the nature of our association with these health-associated bacteria and eventually to exploit them to promote health," the authors write.

The hope is that such research may open the door for personalized probiotic therapies that may reduce the risk for obesity-related diseases. In particular, the current study suggests that increasing the amounts of Christensenellaceae may help to prevent or reduce obesity.

The article also underscores the value of large microbiome studies to uncover the role of the microbiome in health and disease. Tim Spector, MD, head of the Department of Twin Research and Genetic Epidemiology at King's College London, United Kingdom, and coauthor of the study, said in a press release: "Twins have been incredibly valuable in uncovering these links — but we now want to promote the use of microbiome testing more widely in the UK through the British Gut Project. This is a crowd-sourcing experiment that allows anyone with an interest in their diet and health to have their personal microbes tested genetically using a simple postal kit and a small donation via our website. We want thousands to join up so we can continue to make major discoveries about the links between our gut and our health."

The authors have disclosed no relevant financial relationships.

Cell. 2014;4:789-799. Abstract

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