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How genes shape body weight by affecting gut microbes

Our genetic makeup influences whether we are fat or thin by shaping which types of microbes thrive in our body, according to a study published by Cell Press in the journal Cell. By studying pairs of twins, researchers identified a specific bacterial family that is highly heritable and more common in lean individuals. Moreover, a member of this class of bacteria protected against weight gain when transplanted into mice. The findings pave the way for personalized probiotic therapies that are optimized to reduce the risk of obesity-related diseases based on an individual’s genetic makeup.

“Up until now, variation in the abundances of gut microbes has been explained by diet, the environment, lifestyle, and health,” says senior study author Ruth Ley of Cornell University. “This is the first study to firmly establish that certain types of gut microbes are heritable–that their variation across a population is in part due to host genotype variation, not just environmental influences.”

Both genetic variation and the composition of gut microbes have previously been linked to metabolic disease. Despite these shared effects, the relationship between genetic variation and the diversity of gut microbes was largely unknown. Moreover, previous studies in human twins failed to reveal an effect of genetic variation on the diversity of gut microbes. Ley and her team suspected that these studies simply did not analyze enough individuals to achieve significant results.

To address this shortcoming, the researchers sequenced the genes of microbes found in fecal samples from 416 pairs of twins. They found that the abundances of specific types of microbes were more similar in identical twins, who are genetically the same, than in fraternal twins, who are genetically no more similar than ordinary siblings but like identical twins share environmental influences even from the womb. The findings firmly demonstrate that human genes influence the composition of gut microbes.

The type of bacteria whose abundance was most heavily influenced by human genetics was a recently identified family called Christensenellaceae. Members of this health-promoting bacterial family were more abundant in lean individuals than in obese individuals. Moreover, mice that were treated with a specific member of this bacterial family gained less weight than did mice that did not receive this treatment, suggesting that manipulation of the abundance of this type of microbe may prevent obesity in humans.

“Our results showing that bacterial abundances run in families may be useful for disease risk prediction,” Ley says. “The microbiome is also an attractive target for therapeutic manipulation. By understanding the nature of our association with these health-associated bacteria, we could eventually exploit them to promote health.”


Cell, Goodrich et al.: “Human genetics shape the gut microbiome.”

Cell Press