Our health is significantly impacted by the dynamic microbial communities we carry in and on our bodies, especially the one in our gastrointestinal tract - the gut microbiome. Many factors influence the composition of that microbiome, including our environment, the foods we eat and the medicines we ingest. Our genes also impact those microbes, which have genes of their own. It’s a complex system, to be sure, but now scientists are learning more about how small variations in gene sequences can affect the gut microbiome.
Reporting in PLOS Genetics, researchers led by Federico Rey of the University of Wisconsin - Madison have used a mouse model to investigate how small changes in various genes related to bile acids influence the mouse microbiome. They found genetic variants that alter bile acid levels, and that can influence the size of a specific microbial population in the gut.
Bile acids sit at the intersection of gut bacteria and the genome of an individual. The host’s body uses the instructions in the genome to generate bile acids, which help break down the food we ingest so that nutrients can be absorbed by the small intestine. The bile acids can encourage the growth of some microbes and discourage the expansion of others in the intestine. Bacteria there can also metabolize and modify the bile acids, producing secondary bile acids in the process, which also affect the host’s digestion.
In this work, the scientists assessed 400 mice with diverse genomes, to identify the genetic variations that had an impact on the gut microbiome. They hypothesized that bile acid variants are related to differences in the microbiome. They zeroed in on a gene that encodes for a protein that absorbs bile acids in the last section of the small intestine so the acids can be sent back to the liver; the protein is called the ileal bile acid transporter. Small changes in this gene can affect the levels of a bacterial group called Turicibacter, and influence how much of a bile acid metabolite is present in the blood.
"We are interested in identifying the microbial functions that are under host genetic control," said study author Federico Rey, "and future studies will integrate additional metabolomic, metagenomic and transcriptional data derived from the host intestine."
This research can help show how to identify relationships between the microbes we carry in our guts and specific aspects of our physiology. Much more work will be needed to fully understand how host genetics, the microbiome, the environment, and host health are all connected, but studies like this one are a start.
In the research talk in the video above, Rey discusses metabolites made by the microbiome.