The missing variability of the Human Gut Microbiome what is the role of host genetics?

The human intestinal tract contains billions of bacteria and archaea, they train our immune system, digest food and provide energy, and at the same time defend host against infectious bacteria. Studies have identified multiple environmental factors affecting the gut flora composition: diet, living habits, gender and disease have great impact. However, much less knowledge is there for the effects of host genetics, and none for the interplay of various factors. As there is still a surprisingly large part of the microbiome differences among humans that we haven't been able to explain, they could be due to not yet studied environmental factors, the host’s genetic background, or a combination of both. Here, we will take advantage of the recently initiated "Flemish Gut Flora Project" that will determine the gut microbiome composition and host genetics in more than 3000 individuals, where extensive metadata and medicine usage are available, and combine it with knowledge from a 1400 individual cohort from Germany. We aim to first quantify the relative importance of genes versus environment on shaping the gut microbiome, and disentangle possible complex interactions between them; second, focusing on previously neglected genetic variation, taking large insertions, deletions and rearrangements as well as gene copy number variation into account; and last, discover specific interactions between drug usage and genes, to understand how they together interact with the microbiome.