Sleep apnea’s hidden heart disease trigger found in the gut

The findings, presented at ASM Microbe 2026, point to a potential new target for preventing and treating cardiovascular complications linked to sleep apnea.

How Sleep Apnea Affects the Body

Obstructive sleep apnea causes repeated pauses in breathing throughout the night. These interruptions reduce oxygen levels and increase carbon dioxide in the body, triggering a range of harmful effects.

Earlier studies have shown that low oxygen levels can alter bile acids, substances produced by the liver, stored in the gallbladder, and released into the intestines to help digest fats. Beyond digestion, bile acids also serve as chemical messengers that interact with receptors throughout the body.

Researchers had previously found that gut microbes can modify bile acids and influence the amount of atherosclerosis, or fatty plaque buildup in the arteries, that develops over time. Because bile acids enter the bloodstream, they can affect tissues and organs far beyond the digestive system.

"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?" said study first author Celeste Allaband, DVM, Ph.D. from the University of California, San Diego.

Testing a Key Bile Acid Receptor

To investigate, the team studied two groups of mice. One group consisted of mice genetically prone to heart disease, known as ApoE knock-outs. The second group included mice that were also prone to heart disease but lacked a bile acid receptor called the farnesoid X receptor (FXR). These animals are known as ApoE/FXR knock-outs.

Both types of mice were exposed either to normal sleeping conditions with room air or to conditions designed to mimic sleep apnea. Throughout the study, researchers analyzed fecal samples to track changes in gut microbes and metabolites. At the end of the experiment, they examined plaque buildup in the animals' arteries.

Less Plaque and a Healthier Gut

The results highlighted an important role for FXR in the development of cardiovascular disease during sleep apnea-like conditions.

"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."

Mice lacking the receptor developed significantly less plaque in the aorta and aortic arch, although some plaque remained in the pulmonary artery. The researchers also observed that sleep apnea-like conditions had a smaller impact on both the gut microbiome and the metabolome when FXR was absent.

"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.

Future Sleep Apnea Treatments and Probiotics

The team is now pursuing several follow-up studies. One goal is to examine human datasets to determine whether similar patterns can be found in people with sleep apnea.

"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."

If the findings translate to humans, they could open the door to new therapies that target bile acid signaling or use beneficial microbes to reduce the cardiovascular risks associated with sleep apnea.