Individual genes help determine the composition of the gut microbiome

Individual genes help determine the composition of the gut microbiome

Using the house mouse as an example, the researchers investigated how an individual’s genetic makeup affects the composition of the microbiome. Credit: Dr. Leslie Turner

Microorganisms are involved in almost all biological processes on Earth. As an important component of the organism, that is, a complex organism community with colonizing microorganisms, it is an essential building block of life on our planet and of great importance to the health of humans, animals and plants. For several years, scientists at Kiel University, among others, have investigated the extent to which the microorganisms that live in the animal’s gut, the so-called gut microbiome, are involved in controlling diverse life processes and also in the development of disease.

The role of the host genome in this interaction, that is, whether and how the individual genetic makeup It affects the composition of the microbiome, is not yet fully understood. It can be difficult to distinguish the effect of genetic variation from other factors such as changes in the environment of the dead organism. Researchers from the Department of Evolutionary Medicine at Kiel University and the Max Planck Institute for Developmental Biology (MPI-EB) in Plun led by Professor John Baines, along with research collaborator Dr Leslie Turner from the University of Bath, UK, have now investigated this relationship in a A genome-wide association study (GWAS) as part of Collaborative Research Center (CRC) 1182 “Origin and Function of Macroorganisms.” Using hybrid strains of two house mouse subspecies, they found 428 genomic regions in mouse genome which correlates significantly with the abundance of 120 different bacterial taxa in the gut. Furthermore, they showed that many bacterial taxa are inherited, and that these inherited taxa are more likely to interbreed, that is, when two species (for example, a mouse and a certain bacterial species) diversify together, resulting in identical strains. The new findings were recently published by the international research team in the journal eLife.

Microbiome-related genes map

The new work by CRC 1182 researchers is based on two subspecies of the house mouse living in the wild, originating from a hybrid region of central Europe: Mus musculus musculus and Mus musculus localus who live here in a common habitat and can partly interbreed, so their example can be used to observe the effects of genetic differentiation on The composition of the microbiome. The research team studied the inbred lineages of these wild animals, which still possess largely natural microbiome diversity, and analyzed intestinal mucosa In the GWAS study.

“The advantage of working with these hybrid mice is that they have more of that genetic diversity, due to many generations of natural crossbreeding compared to laboratory animals generally used. We chose to focus on bacteria associated with the intestinal cell wall, as these bacteria are most likely to reflect the result of interactions with the host. Thus, the influence of genes on microbial colonization of the gut is best studied there. 120 different bacterial taxa within the microbiome. We were able to narrow this large number down to about 80 high-confidence candidate genes, many of which are known to be involved in bacteria recognition and communication.”

The co-evolution of microorganisms and host organisms

The fact that mice are protospecies also opened up the possibility to investigate the role of the host genome in changes in the microbiome at the interface of differences within and between species. “To do this, we calculated heritability estimates for each bacterial taxon and were able to show that many bacterial taxa were highly genetic. Next, we tested whether these heritability estimates correlated with their respective co-breeding rate and found that bacterial co-breeding appears to be highly genetic,” Turner said. University of Bath Lecturer: “Greater Dependence on Host Genes.”

Thus, a large proportion of microbial species appear to be heritable for successive generations, which may provide a basis for genetic and microbial diversification in the early stages of speciation. “This likely indicates that this inheritance reflects a greater history of host adaptation to common bacteria. Overall, our study is the first to establish a relationship between heritability and the degree of diversity of bacteria with their hosts during the speciation process,” emphasizes Turner.

New approaches to investigate microbiome-related causes of disease

Additionally, to test for potential links to disease development, the research team then searched the animal genomes for genes already known to be associated with human diseases, such as mental disorders and inflammatory bowel disease (IBD). “In those regions of the host genome that are associated with bacterial colonization of the gut, we actually found an accumulation of such genes,” Baines notes.

This opens a new research approach that Baines and his team hope to follow, among other things, in the planned third phase of CRC 1182 funding from the German Research Foundation (DFG). “Understanding the forces that determine variability in bacterial communities within a host species is fundamental to better understanding evolution and function, but also to the disruption of macroorganisms. Our study of the genetic structure of host-microbe interactions provides important new perspectives on this complex interaction,” summarizes the CRC Project Lead. 1182 Baines.

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more information:
Shauni Doms et al, Key features of genetic engineering and evolution of host-microbe interactions revealed by high-resolution genetic mapping of the mucosa-associated gut microbiome in hybrid mice, eLife (2022). DOI: 10.7554 / eLife.75419

Journal information:

Introduction of
Keel University

the quote: Individual Genetics Help Determine Gut Microbiome Composition (2022, Aug 4th) Retrieved Aug 4, 2022 from

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