In fact, the first generation of cholesterol-lowering drugs tried to exploit this mechanism by preventing the recycling of bile acids. But the side effects were unpleasant, and drug companies, for the most part, abandoned this approach.
“If you can understand how these more than 100 different bile acids signal both the small intestine and the liver to use cholesterol, you potentially could design a molecule, like a drug, that could increase the conversion of cholesterol into bile acid with the net effect of reducing serum cholesterol,” he says.
Furthermore, “you potentially could say that the composition of an individual’s intestinal bacteria controls their serum cholesterol levels,” he adds. “That would be a very important finding. Let’s say we identify one specific bile acid that will inhibit our body’s ability to convert cholesterol to bile acid. Let’s say it’s made by one particular strain of bacteria made in the gut. That’s a pretty powerful connection, that having this bacterial strain in the gut could cause you to have cholesterol problems.”
Ultimately, the result could be a drug or a microbiological strategy that would inhibit the bacteria’s ability to make this harmful bile acid, providing a targeted new way to reduce serum cholesterol. “I think this would be a wonderful example of how looking at a very fundamental basic science question could have important translational implications on human health,” he says.