Human genes have an impact on shaping our gut ecosystem. A large, international study by the MiBioGenconsortium, led by the University Medical Center Groningen, analyzed the common genetic factors that influence the composition of the human gut microbiome in more than 18,000 people. The results were published January 18 in the leading scientific magazine Nature Genetics. Haydeh Payami, Ph.D., professor in the Department of Neurology, and Zachary Wallen, a postdoctoral fellow in the Payami laboratory, were collaborating authors on the study.
“The last decade has greatly expanded our understanding of the human microbiome, the trillions of microbes that inhabit the internal and external surfaces of our bodies,” Payami says. “We have come to appreciate their vital role in helping proper human development from infancy to adulthood and their active participationin many human functions: helping us to digest food, training our immune system and, importantly, affecting our brain function via the gut-brain axis.”
The largest and richest human microbiome inhabits the gut and contributes substantially to our health. Yet the factors that shape its composition, although widely studied, remain unclear, and the more than 80 percent difference in gut microbiome between individuals remains unexplained. In general, environmental factors such as diet and medication play a major role; however, a role for human genetic variants has also been suggested by the identification of heritable bacteria, i.e., those that are more common in twins and family members.
Haydeh Payami, Ph.D., professor in the Department of NeurologyNow, the new study from the MiBioGen consortium, an international collaboration involving more than 20 labs across the world, highlights the common host genetic factors that influence the composition of the human gut microbiome in the more than 18,000 people analyzed.
The study says that at least two human genes have a major impact in shaping our gut ecosystem: the lactase gene LCT, which influences the abundance of lactose-digesting Bifidobacteria, and the fucosyl transferase gene FUT2, which determines the abundance of Ruminococcus torques. They also show that other human genes affecting microbiome composition are involved in important aspects of host metabolism, nutrition, and immunity. The analyses stretch as far as establishing relationships between several bacterial species and human diseases. The data converge on humangenes that are most active in the small intestine and brain. These results support the existence of the gut–brain axis mediated by the microbiome and likely influencing gastrointestinal and brain disorders.
“This study is a great example of a large international collaboration and is the first to accurately estimate the effect of host genetics on the gut microbiome,” says Alexandra Zhernakova, one of the principal investigators leading the consortium. “More genetic effects will likely be identified with increased sample size in future studies, but our multi-center approach did identify robust loci that are shared across populations. However, further studies in large and more homogenous groups are essential to identify population-specific effects and gene-environmental interactions.”
“It was a challenge to combine datasets from multiple cohorts due to the large technical differences and to biological variations across populations,” says Alex Kurilshikov, the first author of the study.
“However, this diversity also brings strength—for example, we could see that genetic variants in the lactase gene determine Bifidobacteria abundance in adults, but not in children, and that this effect is more pronounced in European populations. The large sample size also allowed us to apply genetic methods and show that some bacteria are causal for developing diseases.”
Zachary Wallen, a postdoctoral fellow in the Payami laboratoryThe MiBioGen researchers have made their results available to other scientists and the scientific community for additional and future analyses. All results are uploaded to http://mibiogen.org, supported by the Genomics Coordination Center in the Department of Genetics, UMCG.
At UAB, Payami’s research focuses on the gut microbiome as a potential missing link between genetic and environmental causes of Parkinson’s disease. Her research is supported by a four-year, $2.5 million grant from the U.S. Army Medical Research and Materiel Command.
Previously, Payami’s laboratory published findings showing that the composition of the bacteria in the guts of people with Parkinson’s disease differed from healthy controls. The researchers also discovered that Parkinson’s medications were linked to changes in gut bacteria as well. Payami and Wallen recently characterized three clusters of microorganisms that are off-balance in Parkinson’s gut, including the presence of opportunistic pathogens at high levels which they suspect (and are currently testing) may have triggered the development of Parkinson’s in some individuals. They also find unusually elevated levels of bacteria that are commonly sold as probiotic, which could be a warning sign against self-medicating with supplements. ~Bob Shepard