The Gene FUT2 influences the intestinal flora and is a factor in Crohn’s disease.

Risk genes and bacteria play an important role in the susceptibility to intestinal diseases such as Crohn’s disease. Little is so far known about how the two factors influence each other. New insight into this interaction between genotype and intestinal flora has been won by John Baines and his colleagues of the Inflammation Research Excellence Cluster. Their research findings show how the FUT2 gene affects the bacterial communities in the intestines and what it can mean for humans. PNAS currently reports on their study on the website www.pnas.org/content/early/2011/11/08/1106408108.abstract.

Kiel,  November 9^th 2011 FUT2 is a gene that makes sure ABO blood group antigens are not only in blood but also found in bodily secretions, such as tears, saliva and gastrointestinal mucosa. In addition, the property of protecting against various infectious diseases has been attributed to the gene. Whether or not this property can develop depends on whether a person carries a functional gene variant of FUT2 – about 80 percent of the population – or not, which applies to 20 percent of the population. The 20 percent of the population that doesn’t have the functioning FUT2 gene variant enjoy advantages as well: they are, for example, better protected against certain types of viruses, such as the Norovirus. However, there is a very big disadvantage: they are more susceptible to Crohn’s disease, one of the most prevalent chronic inflammatory bowel diseases, which is considered incurable and has a strong influence on the lives of those affected by it.

An interdiscplinary research team conducted the study

These properties of the FUT2 gene were the reason that John Baines, a biologist at the Max Planck Institute for Evolutionary Biology, Plön, and a member of the Inflammation Research Excellence Cluster at Kiel University, and his colleagues began occupying themselves intensively with the gene and its impact on the intestines. Since bacterial communities that have established themselves in the intestines play an important role in the development of diseases, the interactions between FUT2 and the intestinal bacteria became a special focus: “As we began our investigations, we asked ourselves if people with different variants of the FUT2 gene also had differences in the gastrointestinal bacterial communities, both in terms of the number of bacteria, their diversity, and as regards the composition of these bacterial communities. We suspected that any differences in these bacterial communities could explain the increased susceptibility to Crohn‘s disease in people without a functioning variant of FUT2”, said John Baines regarding the preliminary considerations of the study in which 47 people, of which 29 had Crohn’s disease and 18 were healthy subjects, were examined. In order to fully evaluate the findings, an interdisciplinary research team of physicians, evolutionary biologists and geneticists of the Inflammation Research Excellence Cluster was at work. Lead author Philipp Rausch is a doctoral candidate at the Cluster.
Findings show a definite correlation between genotype and phenotype in the intestines
“We were able to observe definite differences within the bacterial communities that are dependent on the different FUT2 variants. Our studies showed, in respect to various aspects of the bacterial community, that they are not only more pronounced between healthy individuals and Crohn’s disease patients, but are also influenced by the functioning of the FUT2 gene. This finding is reinforced by the greater number of bacteria, such as, e.g. Lactobacillus, in the group with a functioning FUT2 gene. These bacteria are attributed as having, among others, a probiotic effect in the intestines. The changes in the compositon of the bacterial communities could thus make carriers of the non-functional FUT2 gene more susceptible to Crohn’s disease, since important bacteria are not able to colonize such intestines.

We attribute the finding to the property of FUT2 that regulates the expression of certain blood group antigens (sugar chains), as there is an interaction between the intestinal bacterial communities and these sugar chains. It is likely that bacteria adapted themselves in the course of their evolution to these “docking sites” or “food sources” and thus a loss of this factor led to a loss of adapted bacteria.”

The significance of the findings: An example for the relationship between genotype and microbiota as phenotype

Through the research findings, the understanding of the relationship between the genotype and the phenotype of a human increases. John Baines: “It appears that the intestinal flora is a phenotype that is partially controlled by the genotype. The more we learn about the connections, the more possibilities there will be for a better and more individualized treatment and prevention of Crohn’s disease.”

The findings of the study are currently available on the website of the renowned scientific journal PNAS: “Colonica mucosa-associated microbiota is influenced by an interaction of Crohn disease and FUT2 (Secretor) genotype”: www.pnas.org/content/early/2011/11/08/1106408108.abstract

The Cluster of Excellence "Inflammation at Interfaces"

The Inflammation Research Excellence Cluster follows a unique, interdisciplinary research approach in order to decode the causes of chonic inflammation and to develop therapies for healing. The research association brings together the competences of approximately200 geneticists, biologists, nutritionists and physicians from Kiel University and the University of Lübeck, the Research Institute Borstel and the Max Planck Institute for Evolutionary Biology, Plön. In Germany alone, millions of people suffer from chronic inflammation of the lungs (asthma), the skin (psoriasis), the intestines (Crohn’s disease) and the brain (Parkinson’s disease). The trigger is a disorder of the immune system: it incessantly activates inflammatory mediators and defense cells, thereby destroying healthy tissue. The number of sufferers increases daily. This phenomenon of modern civilization has become the challenge for 21st Century medicine. Accordingly, in 2007 the German Federal Government and the German Research Foundation declared the decoding of the complex inflammation mechanism to be a national scientific priority.

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