Researchers from Champalimaud Centre for the Unknown in Portugal and the University of Lisbon examined how altered sleeping habits affect gut health. They discovered a group of immune cells that play a role in various gut processes, such as fighting infections and boosting the protective layer of the epithelium. However, these processes can get disrupted among people who go on sleepless nights.
“It comes as no surprise, then, that people who work at night can suffer from inflammatory intestinal disorders,” said co-author Henrique Veiga-Fernandez.
The findings of the study were published in the journal Nature.
Master circadian clock influences immune cells
The body is equipped with its own internal timekeeper called the circadian clock. It serves as a master clock for various circadian rhythms, or 24-hour cycles that make sure bodily functions and processes are optimized at certain times of the day.
Cells follow certain circadian rhythms through their cellular genetic machinery, which is encoded in “clock genes.” These genes work like little clocks that inform cells of the time, which helps organs and bodily systems know if it’s time to perform a certain process.
But while these cell clocks work independently, they still receive input from the brain’s circadian clock. According to Veiga-Fernandez, cells can easily lose track of time because they don’t have direct information about the environment. Thus, they rely on the master clock to get this information and keep their individual clocks up-to-date and synchronized to the body’s overall schedule.
“The job of the brain’s clock, which receives direct information about daylight, is to synchronize all of these little clocks inside the body so that all systems are in sync,” said Veiga-Fernandez.
The team was particularly interested in a particular group of immune cells called type 3 innate lymphoid cells, or ILC3s. These cells play important gut functions, such as fighting infections, controlling the integrity of the gut barrier and instructing lipid absorption. When the researchers disrupted their clocks, they learned that the number of ILC3s in the gut was significantly reduced. This led to severe inflammation, breaching of the gut barrier and increased fat accumulation.
The researchers investigated some more, this time disrupting the master clock to see how it influences the expression of different genes in ILC3s. They found that the “molecular zip code” of ILC3s was missing. This zip code is a protein expressed by the cells on their membrane. It tells ILC3s, which are temporary residents in the gut, how to get to their destination. But without the brain’s circadian input, the cells failed to express this protein, which meant they were unable to reach the gut.
Veiga-Fernandez said that these findings shine a light on why gut health becomes compromised in people who are routinely active at night. When the body is scheduled to feed, the brain’s circadian clock reduces the activity of ILC3s to promote healthy lipid metabolism. But because the gut can be damaged during feeding, the brain’s circadian clock instructs ILC3s to come back to the gut once the feeding period is over. In turn, the ILC3s fight invaders and promote the regeneration of the gut barrier.
“This mechanism is a beautiful example of evolutionary adaptation,” said Veiga-Hernandez. He added that any changes in people’s sleeping habits could have an immediate impact on ILC3s, such as the development of inflammatory bowel disease. This condition refers to disorders that involve the chronic inflammation of the digestive tract, believed to be caused by an immune system malfunction. (Related: Dreamless sleep actually contributes to illness, according to sleep expert.)
By looking at how the brain’s circadian clock affects immune cells, the researchers posit one possible link between the immune and the nervous system.
Brain.news has more on how lack of sleep affects gut health.
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