Jet lag. Daylight savings woes. Exhaustion and insomnia with a side of appetite change and indigestion. We’ve all experienced the side effects, but why are we so sensitive to changes in our schedules? The answer lies in our genetic makeup and, new research suggests, also in the bacterial passengers that make up over half the cells in the human body.
When we think about bacteria, we tend to focus on the ones that make us sick. We’re just beginning to understand the vast importance of the bacteria living inside of and on top of us, collectively called our microbiome. The composition and activity of our microbiome could impact everything from the evolution of breast milk to acne to obesity to depression. New evidence suggests that studying our gut microbiome could also help to address multimillion-dollar health problems like insomnia and seasonal depression.
According to a recent study at the Weissman Institute of Science in Israel, we rely on bacteria to help establish and maintain rhythmic changes throughout the day that prepare us for different activities like sleep or digestion of a large meal. These cycles, called circadian rhythms control our energy levels, mood, appetite, and more. Circadian rhythms are carefully controlled by changes in the activity of our genes to make sure we don’t crash too early or crave midnight snacks.
You can think of the genetic information in each of your cells as a massive and diverse orchestra where only certain musicians (genes) play at any given time to produce a symphony that fluxes in volume and tempo. The symphony is conducted by a group of circadian genes with clever names like “period,” “chryptochrome,” and “clock.” Circadian genes are found everywhere in nature including plants, animals, and bacteria.
When we travel our clock is reset, and it takes time for our cells to adjust to the new schedule. To find out if our bacterial passengers also feel the effects of a change in time zones, researchers looked to mice. Remarkably, bacteria move around the gut of lab mice in 24-hour cycles. In addition to changing locations, the bacteria also secrete different compounds depending on the time of day. The same patterns were not seen in mutant mice with dysfunctional circadian genes. This suggests that a mouse’s circadian rhythm influences the cyclic patterns of the bacteria in its gut.
If the mouse’s schedule influences the bacteria’s rhythm, could the activity of the bacteria also influence the mouse’s clock? To find out, researchers treated mice with antibiotics to wipe out most of the bacteria in their guts. While the mice behaved similarly, and took their meals at the same time, the activity of many of their clock genes changed. Not surprisingly, most of the pathways affected by these changes were involved in metabolism. That means not only does our circadian rhythm influence the bacteria in our guts, but the bacteria’s circadian rhythm could affect us too.
If the circadian rhythm of our bacterial passengers can affect our body’s normal functions, changes to our microbiome could impact our health even when we’re not traveling. Such changes could have deadly consequences as even the ability of our livers to detoxify substances like acetaminophen, the active ingredient in Tylenol, fluctuates throughout the day. The same pattern was not seen in mice with altered circadian rhythms. In both antibiotic-treated mice and mutant mice with dysfunctional circadian genes, liver function was not affected by the time of day. This means that the circadian rhythm of our microbiome could actually alter the function of essential organs.
These findings suggest that the bacteria in your gut act as a type of “circadian organizer” that has coevolved to help us adjust to different needs throughout the day such as mealtime or sleep. We are just beginning to understand the relationships between the circadian rhythms of bacteria and their hosts. When they’re thrown out of sync, indigestion, insomnia, or even impaired liver function could result. Future studies on the biological clock of our microbiome could help us learn to cope with or even prevent circadian rhythm related ailments. Imagine a future where cultured bacteria trained to certain time-zones could treat seasonal depression or help travelers pre-adjust to their destination.
For any scientists in the room, check out this graphical abstract!