Blood group helps determine composition of gut microbiome

Research team from Kiel University demonstrates connections of certain gene variants with the composition of bacterial colonization in the human body in large genome study

For several years, scientists worldwide have been investigating the extent to which the microorganisms living in and on the human body influence central life processes and thus health and disease. Today, they assume that there is a connection between the entire microbial population, the human microbiome, and the development of diseases. Specifically, inflammatory bowel disease (IBD) is likely to be closely linked to the composition and balance of the gut microbiome. However, how the microbiome and disease development are causally linked and what determines the composition of the microbiome in an individual is still largely unclear.

Researchers at Kiel University (CAU) have now investigated possible influences of genetics, i.e. individual human genetic information, on the characteristics of the microbiome. To this end, they have searched for concrete links between genetics and colonizing microorganisms in a large-scale genome study with data from around 9000 subjects. The research team from the Institute of Clinical Molecular Biology (IKMB), led by Professor Andre Franke, was able to prove, among other things, a previously unknown connection between genetic variations responsible for the blood group and the occurrence and frequency of certain bacterial species. The researchers, who are part of the CAU Collaborative Research Center (SFB) 1182 “Emergence and Functioning of Metaorganisms”, published their results today in the renowned journal Nature Genetics.

Individual genetic makeup influences microbiome

The new publication by the Kiel research team builds on findings from a smaller study that found initial evidence of the influence of genetic variation on the gut microbiome. Now the scientists have succeeded in analyzing gut microbiome samples from five extensive cohorts from three German sites – primarily Kiel, Augsburg and Greifswald – making this the largest so-called genome-wide association study (GWAS) in Germany. In the process, the research team came across 38 conspicuous so-called genetic loci, i.e., the physical positions of individual genes within the overall genetic information, which indicate a connection between individual genetics and the composition of the microbiome.

“We made the most interesting observation in the context of the genetic factors responsible for the expression of the blood group in humans,” highlights first author Dr. Malte Rühlemann, a scientist at the Kiel IKMB and SFB 1182 member. “These genes, which are responsible for the AB0 blood group system, decide whether a person belongs to one of the blood groups grouped within it. In some people, the so-called ‘secretors’, these blood group antigens are not only formed on the surface of red blood cells, but are also released into the intestine. These are mainly sugar residues, which can presumably be used as an energy source by some bacteria of the Bacteroides group, so that they occur more frequently. Particularly in people with blood groups A, AB or B, the mechanism thus seems to directly favor the occurrence of these bacteria in the human intestine,” Rühlemann continued.

This connection has potentially great health significance, because in about 20 percent of the global population belonging to the ‘non-secretor’ group, as well as in people with blood group 0, the release of sugar residues falls away and their microbiome composition deviates as a result. “These metabolites appear to be important molecules in the interaction of the host and a wide variety of microorganisms,” explains Rühlemann, who also conducts research in the Precision Medicine in Chronic Inflammation (PMI) Cluster of Excellence. “Previous studies have shown that people without this secretion pathway are better protected against norovirus infections, for example,” Rühlemann adds. In the research group of SFB 1182 member and co-author Professor John Baines from the Institute of Experimental Medicine, these metabolic pathways have been intensively studied for several years.

The example illustrates the effects that individual genetic variation has on human metabolism and can thus help determine the composition of the microbiome. The researchers hope to gain a better understanding of the detailed mechanisms underlying this interaction between humans and microorganisms in the future. On a larger scale, the new findings of the Kiel research team provide further explanations for the formation of the human microbiome as a whole: in addition to environmental and nutritional influences, the genetics of the human body is apparently also a central factor influencing the bacterial colonization of the body. Thus, the microbiome would be more than a random assortment of microorganisms available in the environment.

Therapeutic targets in the gut microbiome?

In order to be able to deduce clear causal relationships between the bacterial colonization of the body and the development of disease in the future, the Kiel researchers in SFB 1182, in the Cluster of Excellence PMI and within the CAU research group miTarget want to gradually identify further factors that contribute to the composition and balance of the gut microbiome. One approach will be to identify individual critical bacterial species whose occurrence and abundance, both as risk and protective factors, significantly influence the microbial colonization of the body. “Our analyses of large amounts of genetic data in the context of the largest possible cohort studies will provide clinicians with valuable clues in this search as to where they can best intervene in the microbiome in order to specifically treat diseases based on disturbed bacterial colonization in the future,” emphasizes Professor Andre Franke, member of SFB 1182 and Cluster of Excellence PMI as well as spokesperson of the miTarget research group. “The identification of such therapeutic targets is an important first step on the way to a future treatment of, for example, chronic intestinal inflammation by targeted changes in the composition of the microbiome,” Franke continues.

Further information:

Original press release Kiel University

Genome-wide association study in 8,956 German individuals identifies influence of ABO histo-blood groups on gut microbiome. Nature Genetics DOI: 10.1038/s41588-020-00747-1

Scientific contact:

Dr. Malte Rühlemann
Genetics und Bioinformatic Group,
Institute for Clinical Molecular Biology, Kiel University / UKSH
+49 (0) 431-500-15132
m.ruehlemann@ikmb.uni-kiel.de