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Study explores genetic differences among people’s gut microbes, and their health consequences

Scientists have learned a lot in recent years about the gut microbiome—the vast assortment of bacteria that line our intestines—and its role in health and disease. But many studies have neglected a big question: What if the same microbe behaves differently in different people?

New research published in Nature now reveals that small differences in the genomes of microbes affect the overall health of their human hosts. The findings could help in the search for more-targeted probiotics for various diseases.

David Zeevi, who started the investigation at the Weizmann Institute of Science and is continuing it as a fellow in physics and biology at Rockefeller, developed algorithms to systematically identify genetic variants across human-gut microbiomes. In analyzing nearly 900 Israeli subjects, Zeevi and his colleagues discovered around 100 variants in microbial DNA associated with risk factors for disease, whose presence was later confirmed in a separate Dutch cohort.

For example, one of these variants appeared to be related to body weight—people whose gut microbes carry it were found to be 13 pounds lighter on average compared to those who had the same microbe without that particular variant. The scientists subsequently found that this variant gives the microbe the ability to convert certain sugars into a metabolism-augmenting substance—providing a possible explanation for how the bacterial gene might curb weight gain in its human host.

“The real potential of our approach,” says Zeevi, “is that it allows us to not only find such associations, but to then explore the actual mechanisms behind them, giving us a better idea of how to design probiotics and treatments to make people healthier.”