Genes Shape the Gut Large Study Identifies 11 Genomic Regions Influencing the Microbiome

Large-scale genetic analyses are shedding new light on how human DNA shapes the gut microbiome. Drawing on data from 28,000 individuals, two international studies identify 11 genomic regions that influence which bacteria colonise the intestine and how they function.

In two new studies on 28,000 individuals, researchers are able to show that genetic variants in 11 regions of the human genome have a clear influence on which bacteria are in the gut and what they do there. Only two genetic regions were previously known. Some of the new genetic variants can be linked to an increased risk of gluten intolerance, haemorrhoids and cardiovascular diseases.

The community of bacteria living in our gut, or gut microbiome, has become a hot research area in recent years because of its great significance for health and disease. However, the extent to which our genes determine which bacteria are present in our intestines has been unclear. Until now, it has only been possible to link a few genetic variants to the composition of the gut microbiome with certainty.

Gut Bacteria from 28,000 Individuals

Now, in two coordinated international studies, researchers have conducted the most comprehensive investigation so far of the link between the genome and the gut microbiome. The researchers have analysed genetic data and gut bacteria from over 28,000 individuals. They have also carefully surveyed the bacteria the participants have in their intestines. Each individual carries hundreds of different bacteria species.

The analysis identified 11 genetic regions that affect both the bacteria present in the gut and the roles they play. Several of the genes are associated with fundamental processes in the gastrointestinal tract, for example, how nutrients are absorbed and how the body reacts to the bacteria.

“We have learnt a lot about the role played by genetics in the gut microbiome. Several of the genetic connections that we found have to do with very specific biological mechanisms. These concern, for instance, which molecules are present on the surface of gut cells and are thereby available as food for bacteria. They also relate to the way in which the gut reacts to molecules produced by bacteria,” says Tove Fall, Professor of Molecular Epidemiology at Uppsala University, who is responsible for one of the studies.

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Clear Associations Between Genetic Variants and Disease Risk

The researchers also saw clear connections between some of the genetic variants and several diseases. The diseases investigated had been previously linked with the gut microbiome.

“We saw that some of these genetic variants were linked to the risk of gluten intolerance, haemorrhoids and cardiovascular diseases. This suggests that changes in the composition of intestinal bacteria could provide a way to better understand how genetic risks affect health,” says Claes Ohlsson, Professor at the University of Gothenburg, who led the other study together with Kristian Hveem, Professor at the Norwegian University of Science and Technology (NTNU).

The biobanks that the researchers have built up are among the largest in the world for gut microbiome.

“Given that many aspects of our health are linked to the gut microbiome, we naturally want our research to contribute to better ways of preventing and treating diseases by paying attention to the interaction between genes, gut biology and the microbiome,” says Fall.

Original Article: Genome-wide association analyses highlight the role of the intestinal molecular environment in human gut microbiota variation; Nature Genetics; DOI:10.1038/s41588-026-02512-2

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