Bile acids are essential for regulating cholesterol, fat and sugar metabolism. Now, researchers have identified new microbiota-derived molecules that can help regulate bile acid production.

The findings, published in Nature, offer insights for treating metabolic conditions such as diabetes.

Bile acids are produced in the liver and modified by the gut microbiota. While certain bile acids help regulate their own production, whether other modifications of these molecules could influence their metabolism remains unclear.

Researchers led by Tae Hyung Won at Cornell University in New York compared germ-free mice and animals with a healthy microbiota to identify new bile acid derivatives.

Bile acid metabolism

The researchers discovered a previously unrecognized family of microbiota-dependent bile acid derivatives called BA–MCYs. Although germ-free mice produced some BA–MCYs, experiments showed that both the host and its gut microbiota are involved in their metabolism.

Indeed, germ-free mice had lower levels of BA–MCYs compared to animals with a normal microbiota. But when human microbiotas were transferred to the guts of germ-free mice, the animals showed increased levels of BA–MCYs. 

A diet high in fiber, which raises free bile acids levels, also increased BA–MCY levels in mice, the researchers found. This discovery suggests that free bile acids levels can regulate the production of BA–MCYs.

Therapeutic potential

Next, the team tested how BA–MCYs influence the activity of a key protein involved in bile acid production. While free bile acids activated this protein, BA–MCYs reduced its activity. The findings suggest that BA–MCYs contribute to regulating the production of bile acids and balancing their effects.

Giving mice on a high-cholesterol diet certain BA–MCY derivatives reduced the accumulation of fat in the liver, indicating its potential for treating liver conditions and related metabolic disorders.

The findings highlight the importance of the host-microbiota interaction in maintaining a balanced system for bile acid production and regulation, the authors say.