Sleep Apnea's Hidden Heart Disease Trigger Found in the Gut: FXR Receptor Drives Atherosclerosis
核心洞察
Researchers at UC San Diego identified the farnesoid X receptor (搜索) (FXR) as a central driver of arterial plaque buildup during sleep apnea-like conditions in mice.
Mice lacking the FXR receptor developed significantly less plaque in the aorta and aortic arch, with minimized disruptions to the gut microbiome.
The study, presented at ASM Microbe 2026, suggests microbially modified bile acids signaling through FXR are key to cardiovascular complications in sleep apnea.
A new study presented at ASM Microbe 2026 has uncovered a mechanistic link between obstructive sleep apnea (搜索) and cardiovascular disease that runs through the gut, identifying the farnesoid X receptor (搜索) (FXR) as a central mediator of arterial plaque formation during sleep apnea-like conditions.
Researchers from the University of California, San Diego demonstrated that microbially modified bile acids signal through FXR to drive the buildup of fatty plaques in arteries, and that removing this receptor in mice significantly reduced atherosclerosis (搜索) while preserving gut microbiome integrity.
"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 UC San Diego.
The Gut–Heart Axis in Sleep Apnea
Obstructive sleep apnea (搜索) causes repeated pauses in breathing throughout the night, reducing oxygen levels and increasing carbon dioxide in the body. Earlier studies established that low oxygen levels can alter bile acids — compounds produced by the liver, stored in the gallbladder, and released into the intestines to digest fats. Beyond their digestive role, bile acids also function as chemical messengers that interact with receptors throughout the body.
Because bile acids enter the bloodstream, they can affect tissues and organs far beyond the digestive system. The UC San Diego team had previously shown that gut microbes can modify bile acids and influence the amount of atherosclerosis (搜索) that develops over time.
FXR Knockout Yields Striking Results
To investigate FXR's role, the researchers studied two groups of mice: ApoE knock-outs, which are genetically prone to heart disease, and ApoE/FXR knock-outs, which are prone to heart disease but lack the FXR bile acid receptor. Both groups were exposed either to normal room air sleeping conditions 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.
"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 FXR 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.
Identifying Key Bile Acids and Microbes
"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 findings point toward a potential new therapeutic target for preventing and treating cardiovascular complications linked to sleep apnea, a condition affecting millions of patients worldwide.
Future Directions: From Mice to Humans
The research 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.