But now, a group of Henrique Veiga-Fernandes at the Champalimaud Centre for the Unknown in Lisbon, Portugal has discovered that the function of a group of immune cells, which are known to be strong influencers in gut health, is directly controlled by the brain’s circadian clock.
The underlying cause for weight gain and gut inflammation in those who suffer from sleep deprivation has been the subject of many studies that tried to relate physiological processes with the activity of the brain’s circadian clock. Until this newest study published in the scientific journal Nature, it was unknown how the body’s cells and circadian clock were tied together.
“Sleep deprivation, or altered sleep habits, can have dramatic health consequences, resulting in a range of diseases that frequently have an immune component, such as bowel inflammatory conditions,” says Veiga-Fernandes, the principal investigator who led the study. “To understand why this happens, we started by asking whether immune cells in the gut are influenced by the circadian clock.”
The brain’s circadian clock is generated in response to the daylight cycle. Almost all cells in the body follow the circadian rhythm through the expression of what are known as “clock genes.” This is what helps to inform the cells of the time of day, helping the organs and systems that the cells make up together, anticipate if it’s time to rise, eat, or sleep.
Cells Need to Be Synchronized
Veiga-Fernandes explains, “Even though these cell clocks are autonomous, they still need to be synchronized in order to make sure that “everyone is on the same page”. “The cells inside the body don’t have direct information about external light, which means that individual cell clocks can be off. 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 synch, which is absolutely crucial for our wellbeing”.
There are a variety of immune cells present in the intestine, but the research showed that Type 3 Innate Lymphoid Cells (ILC3s) were particularly susceptible to perturbations of their clock genes. “These cells fulfill important functions in the gut: they fight infection, control the integrity of the gut epithelium and instruct lipid absorption”, explains Veiga-Fernandes. “When we disrupted their clocks, we found that the number of ILC3s in the gut was significantly reduced. This resulted in severe inflammation, breaching of the gut barrier, and increased fat accumulation.”
The research showed that by disrupting the brain’s circadian clock, the ILC3s, would not localize in the intestine. In order for ILC3s to stay where they should in the intestine, they need to express a protein on their membrane. This ‘tag’ tells ILC3s, which are transient residents in the gut, where to migrate. With an absence of the brain’s circadian inputs, ILC3s failed to express this tag, which meant they were unable to reach their destination.
This study offers clarity on why gut health becomes compromised in individuals who are active during the night or have sleep disorders. Veiga-Fernandes concluded the study by saying, “This mechanism is a beautiful example of evolutionary adaptation. During the day’s active period, which is when you feed, the brain’s circadian clock reduces the activity of ILC3s in order to promote healthy lipid metabolism. But then, the gut could be damaged during feeding. So after the feeding period is over, the brain’s circadian clock instructs ILC3s to come back into the gut, where they are now needed to fight against invaders and promote regeneration of the epithelium.”