Genes and diet regulate fungi in the gut

Lübeck study on the relationship between fungal colonization in the gut, host genetics and nutrition published – Host genes influence microbiome.

Nutrition has a significant impact on the composition of the microbiome, the colonization by microorganisms, especially in the gut. The mammalian gut is colonized by a variety of beneficial microorganisms that have an important function in health. A disturbance of the balance of the intestinal flora, which is composed of bacteria and fungi, among others, can contribute decisively to the development of diseases such as chronic inflammatory bowel diseases, cancer or autoimmune diseases.

In contrast to the influence of bacteria in the microbiome, the role of fungi is virtually unexplored. In a study, an international team of researchers led by the Lübeck Institute of Experimental Dermatology (LIED) was able to show for the first time that certain fungi in the intestinal microbiome are regulated by host genes and nutrition. The work was published in the journal Nature Communications.

The mammalian gut harbors a diverse microbial ecosystem, the composition of which interacts with the host organism in various ways. Genetic analyses have shown that the interplay of host genetics, bacteria and environmental factors influence metabolism and the immune system, among other things. However, the role of fungi in these complex interactions has not been adequately explored.

Nutritional forms investigated

To address this fundamental question, genetically different mice were fed three different diets over a period of six months: a control diet, a Western diet (high in fat, salt, and sugar), or a calorie-reduced diet. At the end of feeding, the composition of the intestinal flora (bacteria and fungi) was determined using genetic analysis. In particular, in the animals fed the Western diet, there were drastic changes in the composition of the intestinal microbiome. The Western Diet resulted in, among other things, a significant increase in fungi of the genus Wallemia.

“An occurrence of this genus is associated with the development of a whole range of chronic inflammatory diseases, some of them severe, and even certain malignant tumors. Therefore, the basic findings of our study on the influence of diet on the composition of intestinal flora can contribute to disease prevention,” explains Prof. Ralf Ludwig, head of the Lübeck Institute of Experimental Dermatology and corresponding last author of the study.

Another part of the work investigated whether the presence of certain fungi or bacteria in the intestine is associated with certain genes in the mouse. Here, both the composition of bacteria and fungi in the gut were found to be associated with specific, but different, genes. “We were surprised to find that certain microorganisms associated with the same genes that are linked to certain diseases,” Ludwig said. In the future, this knowledge could be used to influence the microbiome in certain individuals through a targeted intervention so that it has a composition that is not associated with certain diseases.

The work was made possible by support from the German Research Foundation: the Excellence Cluster Precision Medicine in Chronic Inflammation (EXC 2167), the Collaborative Research Center Pathomechanisms of Antibody-mediated Autoimmunity (SFB 1526), the Graduate Colleges Modulation of Autoimmunity (GRK1727) and Genes Environment and Inflammation (GRK1743).

Original publication:
Gupta, Y., Ernst, A.L., Vorobyev, A. et al. Impact of diet and host genetics on the murine intestinal mycobiome. Nat Commun 14, 834 (2023).

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