Can Gut Bacteria Whip Your Circadian Rhythms and Your Weight Into Shape?

by Kristina C. - July 25, 2016

Science writer , from Victoria, BC, is a freelancer whose work has appeared in publications throughout North America and Europe. She currently worked as a web editor for the Gut Microbiota for CanadaPharmacyOnline

It's late, and you're struggling to keep your eyes open. But don't feel bad if you can't resist: you're fighting against not only the weight of your eyelids, but also against the instructions of your genes. That is, certain 'clock genes' in your body turn on and off in a roughly 24-hour cycle, initiating molecular changes in different body tissues and telling you, for example, when you need to sleep. The circadian clock is the name given to these mechanisms that drive daily rhythms, which are coordinated by pacemakers in the brain such as the hypothalamic suprachiasmatic nucleus.

Photo Credit by Kristina Campbell
Photo Credit by Kristina Campbell

The circadian clock is like a bootcamp instructor, telling your body what to do when, in no uncertain terms. It has a huge influence on how your metabolism is regulated—and hence, on your weight. For example, human studies show changing your sleep pattern (as in shift work or jet lag) can lead to increased appetite and a heightened risk of obesity and diabetes.

SEE ALSO: The Science of Using Bacteria to Hack Your Emotions

But even the bootcamp instructor can get instruction from elsewhere. Lately, scientists are beginning to understand that events in your intestinal tract—that is, your gut—can boss your circadian clock.

One clue about the gut's involvement was uncovered in a mouse study by Leone and colleagues in 2015, which found that dietary changes could impact the circadian clock. When the mice in the study consumed a regular diet, everything was hunky dory: their circadian clocks worked normally and they maintained a normal body weight. Not only that, the beneficial bacteria produced molecules called short-chain fatty acids (SCFAs) at levels that varied cyclically.

But when the mice consumed a high-fat diet, this all fell apart. In these mice, there were no more oscillations of the SCFA molecules, but there were oscillations of another molecule, hydrogen sulfide. These ended up influencing the expression of circadian clock genes in the liver and changing the mice's metabolism to make them obese. The researchers concluded that high-fat diets, by changing the 'messenger' molecules that move between the gut and the liver, profoundly disrupt energy use. This idea was backed up by another study that noted the gut microbes of mice on a high-fat diet didn't fluctuate in a daily pattern as they do in other mice, partly because the high-fat diet made them want to eat at odd times.

All in all, it seems the gut microbiome might be a key element for maintaining the circadian rhythms and a healthy weight. Perhaps gut microbes sense what, when, and how much is eaten and then respond by producing molecules that both influence the circadian clock and control metabolism.

But the gut-circadian clock link doesn't end there. New research shows, in addition to the gut microbiota helping regulate the circadian clock, the circadian clock may affect gut bacteria via hormones. University of Kentucky researchers found that a certain species of human gut bacteria, Enterobacter aerogenes, has its own circadian rhythm and responds to the hormone melatonin.

In the study, researchers first took a species of E. aerogenes and found that it proliferated more rapidly when it was exposed to melatonin. Then they tried to address whether the bacteria had their own circadian clocks: by transforming the bacteria to produce bioluminescence, the researchers observed fluctuations in peak bioluminescence on a 24-hour time scale—evidence that, indeed, the bacteria did have their own circadian rhythms. The bacteria reached peak bioluminescence at random times, but the researchers found that adding melatonin caused the bacterial rhythms to synchronize. This is compatible with the idea that the human circadian clock can give out hormonal signals (like melatonin) that elicit responses from the circadian clocks of gut bacteria. More research could confirm whether this is really the case.

As we unravel the links between circadian rhythms, metabolism, and gut bacteria, a question might seem obvious: Why does the circadian clock have anything to do with the gut? Wouldn't it just be easier if our bodies were flexible enough to handle variations and diet and sleep patterns without messing with our weight?

Scientists still don't really know the answer to this question, but one emerging idea is that circadian rhythms are a way of separating vital body processes in time. That is, if some processes in our body need physical space to be carried out (if, for example, a process requires room for cells to proliferate), they wait until their appointed time to do so. Spaces in our body, like the gut, might be like rooms for rent, with different groups taking over at different organized times.

So far we don't have a lot of control over the metabolic effects of messing with our sleep cycles or diet. In the future, though, perhaps specialized probiotics taken at different times in the 24-hour cycle will be able to manipulate the gut bacterial community to offset these effects.


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