New study shows that genes play a role in microbiome composition

In a new study, a group of researchers from the UMCG who have joined forces as the Groningen Microbiome Team have shown that your genes influence the composition of your gut microbiome. This information is important for understanding the precise role of the gut microbiome in human diseases, and these results provide a new starting point for developing efficient personalised nutritional strategies to prevent diseases or to enhance the efficacy of some disease therapies. The results of the study and a preview of the expected challenges and future perspectives of microbiome studies are published today in Nature Genetics.

Growing understanding of the crucial role of the microbiome

Over the past ten years, our understanding of the human microbiome, especially the microbiome of the digestive track, has expanded rapidly. We now know that the gut microbiome plays an important role in human health and that a healthy microbiome consists of a higher diversity of bacteria that keep each other in balance. Which bacteria occur in the microbiome and their abundance depends to a large extent on external factors like diet, medication and lifestyle. However, in the new study, the researchers show that specific points in our genome also influence the gut microbiome.

Large Lifelines cohort study

In this work the researchers from Groningen Microbiome Team and the UMCG Genetics Department analysed the gut microbiome of 7,738 participants of the Dutch Microbiome Project, a project within the Lifelines Dutch Biobank.

For each participant, the team used high-resolution techniques to map out which bacteria are present and their function. Information about more than 5 million common genetic variants available through the UMCG Genetics Lifelines Initiative was then used to scan the entire human genome for possible associations with the gut microbiome.

Two genetic variations profoundly affect gut microbiome composition and function

The researchers identified two genetic variations that have a major impact on gut microbiome composition and function. The first is the lactase gene, which encodes for the lactase enzyme need to digest lactose (milk sugar) in the stomach. The new study shows that the lactase gene influences the abundance of Bifidobacteria species in the gut. The key metabolic feature of Bifidobacteria are their ability to digest lactose, and the abundance of these bacteria was shown to be lower in participants who consume milk and are genetically predisposed to produce the lactase enzyme.

The other gene identified to impact the gut microbiome is ABO, which determines blood group types. ABO was found to influence bacteria of the Collinsella family, and this association was dependent on another gene, FUT2, that encodes fucosyl transferase. FUT2 determines if an individual secrets the blood group antigens into the gut, making these available to the bacteria as source of energy. Researchers found that both genes also influence the bacterial pathways involved in lactose and galactose degradation.

Overall, the study shows that host genetics can influence gut microbiome composition and function. In general, the overall effect of genetics is modest and smaller than the effect of environment. However, a subset of bacteria are heritable, and for these species the effect of host genetics is comparable to its contribution to common traits such as glucose metabolism or common diseases.

These results are important starting point for gaining a better understanding of the role of gut microbiome in human diseases and for developing efficient personalised nutrition strategies.

What next?

Researchers from the Groningen Microbiome Center are world leaders in studying the relations between host genome and the gut microbiome. As experts, Dr. Serena Sanna, Prof. Alexandra Zhernakova and their colleagues, discussed the next steps in a perspective paper. They estimated that there are likely to be many other genetic variants that influence the microbiome, but to find these, many more participants need to be studied, at least 50,000. This large number of volunteers may soon be reached as both genome analysis and microbiome analysis are becoming routine procedures. Millions of people have now received information on their genome through public genotyping services such as 23andMe. Similarly, microbiome analysis is also becoming more popular with the general public.

The researchers also suggest that future studies should also focus on the bacterial genome. Bacteria of the same type can have small differences in their genomes that may change their activity and function. Thus, this extra information can further help studies aiming to understand specific relations between bacterial genes and human phenotypes. Within the Groningen Microbiome Team, this bacterial genome work is led by Prof. Jingyuan Fu, a co-author of the perspective paper who recently received a Dutch VICI grant to study this topic.

Link to the research and perspective articles:

Genetics research article
Perspective article