The human digestive tract follows a pattern of digesting food and nutrients while awake and replenishing senescent cells while asleep. But shift work and jet lag can disrupt the body clock, which has been linked to increased risks of intestinal infections, obesity, inflammatory bowel disease and colorectal cancer.
Now, researchers at the University of California School of medicine have discovered an immune cell that helps keep the gut healthy. These cells, called type 3 innate lymphoid cells (ILC3), are responsible for keeping the gut functioning normally and healthily. The researchers found that so-called clock genes were highly active in these cells, which produced immune molecules closely related to clock gene activity. When researchers knocked out a key clock gene in mice, the mice were unable to produce a subset of ILC3 cells and had difficulty controlling bacterial infections in their guts.
The findings could help explain why disruptions in circadian rhythms often lead to gastrointestinal problems. In addition, they point out, the clock's genes can affect immune cells and help counteract the negative effects of sleep irregularities associated with bowel disease.
"High strength work, insomnia, chronic sleep deprivation on the destruction of the circadian rhythm is more and more obvious, and have harmful effects on human health, but we still don't know why interrupted sleep can cause these problems," the researchers Bruce r. Stevens said, "now we have found that circadian rhythms directly affects the function of immune cells in the gut, which could help explain some health problems, such as inflammatory bowel disease."
ILC3 cells maintain the balance in the gut. They also produce immune molecules that help the gut immune system avoid overreacting to harmless microbes and food particles, while maintaining its ability to fight disease-causing microbes.
The researchers studied ILC3 cells taken from the intestinal tract of mice every six hours and found that over the course of a day, the activity of clock genes changed in a predictable pattern, with the immune molecules' genetic activity consistent with clock genes. When they had some mice work on a schedule similar to that of shift workers, ILC3 cells stopped working properly. When stimulated to respond to infection, they produce low levels of immune molecules. Mice also failed to grow the normal number of ILC3 cells. Stevens suggests that ILC3 is regulated by circadian rhythms, and that certain key circadian genes are essential for the development and function of ILC3 cells. And the lack of ILC3 cells or changes in ILC3 behavior may affect the body's ability to resist intestinal infections.
"At the same time, in intestinal health, the relevance of circadian regulation may affect medical practice. Stevens says we have to start thinking about the circadian rhythm of gut cells when choosing the best time for nutritional and drug interventions.
Stevens and his researchers will continue to study the role of circadian rhythms in the digestive tract.