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Few health topics have garnered more interest in recent years than the human microbiome — the rich community of microorganisms that share our bodies, from the surface of our skin to the insides of our stomachs. Research is increasingly revealing the many complex ways that these little guys interact with and influence our bodily processes, and a growing scientific consensus suggests that we may need them just as much as they need us.

The microbes in our guts are proving themselves to be among the most essential, if also the most mysterious. Studies have suggested that they can influence everything from our weight to our mood, and disruptions in their natural, healthy structure can have noticeable impacts on our health. Entire diets have been constructed over this conceit.

Now, a growing body of research is suggesting that gut microbes may also be closely linked with our sleep quality, due to their close connection with our circadian rhythms, hormone expressions and other such processes. We’re still just beginning to understand these interactions, and many of the relevant studies so far have focused on mice instead of humans. Still, the research that does exist hints at some fascinating relationships between the little bugs in our stomachs and our nightly rest. 

The Connection Between Microbiome and Circadian Rhythm

Some of the most intriguing recent research has focused on the connection between the gut microbiota and circadian rhythms — the 24-hour cycles the body goes through that regulate processes like sleeping and eating. 

The circadian clock is what helps control when you fall asleep and when you wake up, and is also believed to be linked to the body’s metabolism, helping to control factors like when you’re hungry and how easily you gain or lose weight. Scientists now believe that gut microbes have a lot to do with the regulation of these processes.

One key to the connection is the liver, which helps express genes related to the regulation of the circadian clock. Past research in mice has found that mice specially raised to have no gut microbes at all have livers that function very differently from mice with normal microbiomes, said Eugene Chang, a professor of medicine at the University of Chicago.

“The liver is what is perhaps your major metabolic organ,” Chang explained. “And when we looked at the differences in the sort of profile of genes expressed in the liver of these two groups of mice, we found that a lot of these genes called circadian clock genes were really differentially expressed.”

The study “showed that gut microbes themselves actually have what we call diurnal, or ‘day versus night,’ patterns that are directly tied to our own circadian or diurnal patterns,”

Last year, Chang co-authored a study that built on these observations, revealing a link between diet, bacterial populations in the gut and the expression of genes that help control the circadian clock. He and his colleagues already knew that microbes in both mice and humans change their activity levels throughout the day in a way that suggests they respond to their own circadian rhythms. In addition, these microbes produce substances in the gut that help affect gene expression related to the circadian clock.

The new study showed that the microbes in mice who were fed a high-fat diet — aka relatively an unhealthy diet — did not exhibit the normal kinds of fluctuations throughout the day and produced different substances than those in mice who were fed a more normal diet. Additionally, mice who were specially raised to have no gut microbes did properly express the genes that control circadian rhythm -- and they also had trouble gaining weight, even when fed a high-fat diet. 

In summary, the study “showed that gut microbes themselves actually have what we call diurnal, or ‘day versus night,’ patterns that are directly tied to our own circadian or diurnal patterns,” said the study’s lead author, Vanessa Leone, also of the University of Chicago. “And those interactions appear to be impacted by the type of diet that you take in.”

Other studies have suggested similar links. A 2014 paper, for instance, showed that mice who were both fed a high-fat diet and subjected to sleep disruptions showed significant changes in the structure of their gut microbiota. 

How Gut Bacteria Messes with Hormones and Mood

It’s fairly well established that our hormones and our moods play a big role in the quality of our sleep. And these may also be significantly influenced by gut microbes.

Some previous research in mice has suggested that gut microbes are involved with the regulation of cortisol levels in the body, said Leone. When scientists reduced the amount of gut bacteria in these mice, levels went down.

Cortisol is involved in a number of bodily functions, including metabolic regulation and immune expression — and it’s also thought to be a key player in the sleep cycle. Cortisol levels have been shown to dip to their lowest levels at night when we’re sleeping, and they spike in the morning when we wake up. So disruptions in the microbiome that affect cortisol levels also have the potential to disturb the regular sleep cycle as well. 

Certain gut microbes have exhibited the ability to produce, convert or consume other hormones related to sleep and the circadian rhythm, including melatonin and serotonin

The hormone is also known to affect mood, with high levels of it associated with stress. Leone pointed out that past research has also shown that mice with no gut microbes exhibit higher cortisol levels when they’re put in stressful situations, for example, if they’re forced into small, restrained areas.

“In the absence of gut microbes, those mice are at a heightened level of anxiety,” Leone said. This research could provide another glimpse into the link between the microbiome and sleep, as research in humans has suggested that mood — including problems with stress, anxiety or depression — can heavily influence our sleep quality.

Leone also added that certain gut microbes have exhibited the ability to produce, convert or consume other hormones related to sleep and the circadian rhythm, including melatonin and serotonin. However, scientists are just starting to explore these interactions.

“You kind of have a situation where we know that those hormones are really important for regulating circadian rhythm, but clearly the gut microbes have their own capacity to utilize or produce those hormones as well,” Leone said. “How that feeds into our circadian system isn’t fully appreciated. We’re just kind of now starting to examine the microbial side of that and how that interaction occurs.” 

The Two-Way Street

One especially interesting aspect of all the research described so far is that it suggests a two-way interaction between gut microbes and the factors that influence sleep.

Some studies have shown that disruptions to the microbiome — caused by diet, for instance, or other external factors — can produce changes in hormones or gene expression that could then affect the sleep cycle. Other studies have suggested that disruptions in sleep can feed back in the other direction, causing changes in the gut microbiota.

“The way I see the gut microbiome — it’s an organ of our body,” Chang said. “And that organ is highly sensitive to environmental and dietary changes."

“The way I see the gut microbiome — it’s an organ of our body,” Chang said. “And that organ is highly sensitive to environmental and dietary changes, and also it’s probably very responsive to cues or signals from the person or individual as well.”

On top of this two-way feedback, changes in sleep and the microbiome — caused by any factors — can also team up together to bring about changes in other aspects of the body.

A study earlier this year from Baylor College of Medicine, for instance, explored the connection between sleep apnea, disruptions in the microbiome and hypertension. That study, conducted in rats, found that rodents with both sleep apnea and an imbalanced microbiome were likely to develop hypertension, while those with sleep apnea and a normal microbiome tended to maintain normal blood pressure 

The Human Connection  

It’s important to keep in mind that all of these studies have taken place in mice, rather than humans — so we can’t definitively say the same kinds of effects would take place in our own bodies. Given what’s known about the similarities between the functions of mouse microbes and human ones, however, researchers feel confident that there’s good reason to continue exploring the connections.

And, in fact, at least one group of researchers is in the process of conducting one of the first human studies to examine the link between gut microbes and sleep quality. That project is being led by Amy Reynolds, a research associate at CQ University in Australia, in collaboration with uBiome, a startup that sells microbiome sampling kits and analyzes the samples for consumers.

By analyzing microbiome samples from participants with varying degrees of sleep disruption, the project aims to explore the ways that sleep quality and the gut microbiota influence one another.

When people are sleep restricted, we see changes in their cortisol levels.” And as Leone pointed out before, cortisol is one of the hormones thought to be tightly tied up with healthy microbiome function.

Reynolds, whose background is in psychology, first developed an interest in the subject after studying the ways that shift work — and the unusual sleep schedules that tend to accompany it — affect metabolic health, which is also shown to be linked to the microbiome. “Surely there may be something going on in humans that explains this sleep-microbiota-metabolic relationship,” she says.

The research in mice and rats has already provided a good starting point, she added, so there are already some theories to go on when it comes to the link.

“We know…not getting enough sleep initiates a stress response in your body,” Reynolds said. “When people are sleep restricted, we see changes in their cortisol levels.” And as Leone pointed out before, cortisol is one of the hormones thought to be tightly tied up with healthy microbiome function.

For now, the human study, as Reynolds says, is “still in its infancy” so it will be a while yet before we see any published results. But she has high hopes that the project will help shed some light on what is unfolding into a complex and fascinating series of connections among our body’s processes.