Studies in mice reveal a new target for potentially treating and preventing life-threatening cardiovascular complications in the millions of patients with sleep apnea worldwide. The study, presented at ASM Microbe 2026, showed how microbes modify bile to help protect mice from sleep apnea's heart and metabolic toll.
Obstructive sleep apnea is a widespread sleep disorder where a person's breathing repeatedly stops and starts throughout the night. This deprives the body of oxygen and builds up carbon dioxide, causing a variety of issues in the body. Previous research has shown that the lack of oxygen alters bile acids, which are compounds made by the liver, stored in the gallbladder and released in the intestines to digest fats. However, bile acids also act as chemical messengers to different receptors in the body.
In previous papers, the researchers showed that bile acids can be modified by microbes and affect how much of the fatty plaques on the heart (atherosclerosis) are present at the end of the study. Since bile acids are absorbed into the bloodstream, they can bind to receptors all over the body and cause changes in physiology.
We were pretty sure from our previous studies that bile acids, especially microbially modified ones, were a key to regulating the disease so we wanted to know what happens when one of the key receptors for them are missing - does the disease go away?"
Celeste Allaband, DVM, Ph.D., study first author, University of California, San Diego
Allaband explained that there were 2 types of mice in the study: those prone to heart disease (called ApoE knock-outs) and those prone to heart disease that also have a particular bile acid receptor missing -the farnesoid X receptor (FXR) (these mice are called ApoE/FXR knock-outs). The researchers exposed both types of mice to both normal room air sleeping conditions or sleep apnea-like sleeping conditions. Then the researchers looked at the microbes and metabolites in the gut (via fecal samples) during the study as well as the fatty plaques on the heart at the end of the study.
"Our study shows that the FXR host receptor, which can be activated or deactivated by bile acids, plays a central role in driving the buildup of fatty plaques in the arteries during sleep apnea-like conditions," Allaband said. "Strikingly, when this receptor was removed from the mice, the development of arterial plaques dropped significantly in some areas and disruptions to the gut microbiome were minimized."
The researchers found that knocking out the bile acid receptor resulted in significantly fewer fatty plaques in both the aorta and aortic arch, but there were still some present on the pulmonary artery. They also saw reduced impact of sleep apnea-like conditions on the gut microbiome and metabolome.
"These results tell us that microbially modified bile acids and how they signal through the receptor we knocked out (FXR) seem to be key to the impact of sleep apnea-like conditions in our mouse model. We also identified specific bile acids of interest to explore further," Allaband said.
The researchers are exploring several different avenues to follow up on these results, including checking human datasets to see if they can see similar trends. "We also plan to take some of our key bile acids of interest and see if supplementation of these compounds alone can help prevent or reduce disease," Allaband said. "We may also take some key microbes of interest and see if they can be given preventively as a probiotic. There is lots of exciting future work to come."
Subjective aging predicts poorer sleep health and daytime impairment