Variations in the relative proportions of microbial species making up the gut microbiome apparently contribute to variations in LDL-cholesterol in the bloodstream. Lower LDL-cholesterol sustained over a lifetime produces a slower development of atherosclerotic plaque, and lower risk of consequent cardiovascular disease. While it seems likely there is no one optimal gut microbiome, there are certainly specific improvements that can be achieved for most older individuals. Fortunately, producing lasting changes in the balance of microbial populations making up the gut microbiome is an achievable goal. Fecal microbiota transplantation works well, for example. This is a little explored but potentially quite useful area of medical development.
Researchers analyzed metabolites and microbial genomes from more than 1,400 participants in the Framingham Heart Study, a decades-long project focused on risk factors for cardiovascular disease. The team discovered that bacteria called Oscillibacter take up and metabolize cholesterol from their surroundings, and that people carrying higher levels of the microbe in their gut had lower levels of cholesterol. The results suggest that interventions that manipulate the microbiome in specific ways could one day help decrease cholesterol in people.
The researchers found that species in the Oscillibacter genus were surprisingly abundant in the gut, representing on average 1 in every 100 bacteria. The researchers then wanted to figure out the biochemical pathway the microbes use to break down cholesterol. To do this, they first needed to grow the organism in the lab. Fortunately, the lab has spent years collecting bacteria from stool samples to create a unique library that also included Oscillibacter.
After successfully growing the bacteria, the team used mass spectrometry to identify the most likely byproducts of cholesterol metabolism in the bacteria. This allowed them to determine the pathways the bacteria uses to lower cholesterol levels. They found that the bacteria converted cholesterol into intermediate products that can then be broken down by other bacteria and excreted from the body. Next, the team used machine-learning models to identify the candidate enzymes responsible for this biochemical conversion, and then detected those enzymes and cholesterol breakdown products specifically in certain Oscillibacter in the lab.
The team found another gut bacterial species, Eubacterium coprostanoligenes, that also contributes to decreased cholesterol levels. This species carries a gene that the scientists had previously shown is involved in cholesterol metabolism. In the new work, the team discovered that Eubacterium might have a synergistic effect with Oscillibacter on cholesterol levels, which suggests that new experiments that study combinations of bacterial species could help shed light on how different microbial communities interact to affect human health.
Link: https://www.broadins...rt-disease-risk
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