In the JournalsPerspective

Diet, lifestyle outweigh genetic impact on gut microbiome

Genetics play a surprisingly minor role in shaping the gut microbiome, while environmental factors like diet and lifestyle appear to have the greatest impact, according to new research published in Nature.

These findings provide strong new evidence supporting the concept of modifying the gut microbiota to improve human health, investigators from the Weizmann Institute of Science in Israel concluded.

“We cannot change our genes, but we now know that we can affect — and even reshape — the composition of the different kinds of bacteria we host in our bodies,” study investigator Eran Segal, PhD, of the departments of computer science and applied mathematics, and molecular cell biology at Weizmann, said in a press release. “So, the findings of our research are quite hopeful; they suggest that our microbiome could be a powerful means for improving our health.”

To test the hypothesis that differences in gut microbiota composition between individuals is largely determined by their genes, Segal and colleagues analyzed genotype and microbiome data from 1,046 healthy Israelis who participated in a longitudinal nutrition study. As the Israeli population is highly diverse, the study included participants with varied genetic ancestry, making this setting ideal for the genetic aspect of the study, investigators noted.

They found that the gut microbiome did not significantly correlate with genetic ancestry, and that an individual’s genes play only a minor role in determining their gut microbiota composition, accounting for just about 2% of the variation observed between populations.

An illustration of the human gut microbiota
Genetics play a surprisingly minor role in shaping the gut microbiome

Photo Source: Shutterstock.com

Further, they found genetically unrelated people who lived in the same household showed significant similarities in gut microbiota composition, while relatives with no history of living together shared no significant similarities in their microbiomes.

In contrast, they found that environmental factors like diet, drugs and anthropometric measurements accounted for more than 20% of the gut microbiota variation observed between individuals. They also showed that gut microbiome composition was as good or superior to genetics for predicting clinical measures like BMI, fasting glucose levels, glycemic status, high-density lipoprotein levels, cholesterol, waist and hip circumference, waist-hip ratio and lactose consumption.

“Our results demonstrate that the gut microbiome is predominantly shaped by environmental factors, and is strongly correlated with many human phenotypes after accounting for host genetics,” Segal and colleagues concluded. This suggests that modulating the microbiome to improve clinical outcomes should work across diverse genetic backgrounds, they added. – by Adam Leitenberger

Disclosures: The authors reported no relevant financial disclosures.

Genetics play a surprisingly minor role in shaping the gut microbiome, while environmental factors like diet and lifestyle appear to have the greatest impact, according to new research published in Nature.

These findings provide strong new evidence supporting the concept of modifying the gut microbiota to improve human health, investigators from the Weizmann Institute of Science in Israel concluded.

“We cannot change our genes, but we now know that we can affect — and even reshape — the composition of the different kinds of bacteria we host in our bodies,” study investigator Eran Segal, PhD, of the departments of computer science and applied mathematics, and molecular cell biology at Weizmann, said in a press release. “So, the findings of our research are quite hopeful; they suggest that our microbiome could be a powerful means for improving our health.”

To test the hypothesis that differences in gut microbiota composition between individuals is largely determined by their genes, Segal and colleagues analyzed genotype and microbiome data from 1,046 healthy Israelis who participated in a longitudinal nutrition study. As the Israeli population is highly diverse, the study included participants with varied genetic ancestry, making this setting ideal for the genetic aspect of the study, investigators noted.

They found that the gut microbiome did not significantly correlate with genetic ancestry, and that an individual’s genes play only a minor role in determining their gut microbiota composition, accounting for just about 2% of the variation observed between populations.

An illustration of the human gut microbiota
Genetics play a surprisingly minor role in shaping the gut microbiome

Photo Source: Shutterstock.com

Further, they found genetically unrelated people who lived in the same household showed significant similarities in gut microbiota composition, while relatives with no history of living together shared no significant similarities in their microbiomes.

In contrast, they found that environmental factors like diet, drugs and anthropometric measurements accounted for more than 20% of the gut microbiota variation observed between individuals. They also showed that gut microbiome composition was as good or superior to genetics for predicting clinical measures like BMI, fasting glucose levels, glycemic status, high-density lipoprotein levels, cholesterol, waist and hip circumference, waist-hip ratio and lactose consumption.

“Our results demonstrate that the gut microbiome is predominantly shaped by environmental factors, and is strongly correlated with many human phenotypes after accounting for host genetics,” Segal and colleagues concluded. This suggests that modulating the microbiome to improve clinical outcomes should work across diverse genetic backgrounds, they added. – by Adam Leitenberger

Disclosures: The authors reported no relevant financial disclosures.

    Perspective
    William D. Chey

    William D. Chey

    Rothschild and colleagues present a comprehensive study that dispels myths about the relative contributions of genetics and environment to the composition of the gut microbiome. Their findings have potentially important implications regarding how the microbiome might influence the pathogenesis of a wide range of diseases. Further, if environmental factors exert a significant impact on the gut microbiome, it should be possible to fashion diet interventions, probiotics, or drugs that exert targeted effects on the microbiome that prevent or treat GI and non-GI diseases.

    • William D. Chey, MD
    • Nostrant Professor of Gastroenterology & Nutrition Sciences Michigan Medicine, Ann Arbor

    Disclosures: Chey reports consulting for Nestle Health Sciences and Ritter Pharmaceuticals, research grant funding from Nestle Health Sciences and True Self Foods, and is a patent holder of My Nutrition Health.

    Perspective
    David L. Suskind

    David L. Suskind

    This well organized and thoughtful study emphasizes what smaller studies have also noted: That environmental factors have the greatest impact over the gut microbiome. The strength of the study has to do with its methodology; the investigators use a large cohort of subjects from Israel with varied genetic backgrounds.  They then also used the same analysis in other patient cohorts, validating their initial findings, that environmental factors, and especially diet, have much more to do with an individual’s gut microbiome than their genetic background.

    Outside of the basic science interest to this study, understanding how the microbiome functions, this data helps to solidify potential treatments for chronic diseases like inflammatory bowel disease. Given the fact that we know the environment has such a large impact on the microbiome, and because we know the microbiome plays a significant role in IBD, we can now, with greater confidence, move forward with dietary therapies, having shown that diet truly does impact the microbiome and therefore disease.

    With both clinical and basic science research on the microbiome moving in this direction, there is huge potential for interventions that may be able to treat microbiome-related diseases, not only IBD, but also C. difficile infection, asthma, depression, multiple sclerosis,  the list goes on. As our understanding of the associations between the microbiome and these diseases improve, so does our understanding of the potential interventions that may be effective for changing the microbiome for the better.

    • David L. Suskind, MD
    • Professor of Pediatrics Division of Gastroenterology, Hepatology and Nutrition Seattle Children's Hospital University of Washington

    Disclosures: Suskind reports no relevant financial disclosures.

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