Intestinal health has a close connection with healthy brain function. New research from the University of Tsukuba in Japan suggests that gut bacteria may also influence normal sleep patterns by helping create important chemical messengers in the brain, such as serotonin and dopamine.

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This finding could offer new hope for people who have difficulty sleeping or experience sleep-related health problems, such as insomnia, chronic fatigue, and mental fog.

“We found that microbe depletion eliminated serotonin in the gut, and we know that serotonin levels in the brain can affect sleep-wake cycles,” says the study’s lead author, Prof. Masashi Yanagisawa. “Thus, changing which microbes are in the gut by altering diet has the potential to help those who have trouble sleeping.”

This new research builds on a solid body of previous work, which established that elements of cognition and brain development have a strong link with intestinal microbial health and metabolism. The study appears in Scientific Reports.

Internal and external cues, such as circadian rhythms and eating, significantly affect sleep. Circadian rhythms are essential biological processes or functions that follow a 24-hour cycle based on the body’s internal clock.

One of the most important circadian rhythms is the sleep-wake cycle. Factors that alter or throw off the sleep-wake cycle can cause sleep disturbances.

Intestinal metabolism is closely connected to brain function by way of the circulatory system and vagus nerve, which create a network called the “brain-gut axis” or “microbiota-gut-brain axis.”

Research shows that the gut microbiome (the community of bacteria, viruses, and fungi that live in the gut) has an effect on elements of cognitive function, brain development, memory formation, circadian rhythmicity, and mental health.

When and what people eat affects the composition, size, and daily rhythms of the gut microbiota. Changes to the gut microbiota can alter intestinal metabolism because microbes belonging to the microbiota produce many gut metabolites — the molecules that result from the chemical reactions that occur during the process of digestion.

Therefore, changing their diet may potentially improve a person’s sleep or reduce sleep problems. Should this prove to be the case, it would serve as a natural, fairly simplistic alternative treatment to sleep medications, which can have a range of negative side effects, including daytime drowsiness and gastrointestinal problems.

In the study, the researchers divided 25 genetically identical 8-week old male mice into two groups.

They gave the mice in the experimental group access to water with four commonly used broad spectrum antibiotics. They included the antibiotic treatment to deplete the mice’s gut microbiota. Meanwhile, the other mice — the control group — drank water without antibiotics.

After 4 weeks, the researchers found that the mice that drank the antibiotic water had far fewer intestinal metabolites than the control mice.

“We found more than 200 metabolite differences between mouse groups,” says Prof. Yanagisawa. “About 60 normal metabolites were missing in the microbiota-depleted mice, and the others differed in the amount — some more and some less than in the control mice.”

The team found that the biological pathways that the antibiotic treatment most affected were those that play a role in producing neurotransmitters, the molecules that neurons use to communicate.

The results indicated that the antibiotic treatment totally shut down the tryptophan-serotonin pathway. The microbiota-depleted mice had higher tryptophan levels than the control mice but almost no serotonin. Therefore, it seems that gut microbes are critical to the process that produces serotonin from tryptophan in foods.

The microbiota-depleted mice were also deficient in vitamin B6 metabolites, which are molecules that speed up the production of serotonin and dopamine.

Next, the researchers examined the mice’s brain activity using electrodes that they had implanted in their scalps to record electroencephalogram (EEG)/electromyogram (EMG) signals, which track the electrical activity of the brain.

This step revealed that compared with the control mice, the microbiota-depleted mice experienced more rapid eye movement (REM) and non-REM sleep at night, a time when mice should be active. The microbiota-depleted mice also had less non-REM sleep during the daytime, most of which mice usually spend sleeping.

Finally, the team noted that the microbiota-depleted mice experienced a higher number of REM sleep episodes than the control mice during both the day and night and a higher number of non-REM episodes in the daytime.

These findings suggest that the microbiota-depleted mice were switching more frequently between sleep and wake stages than the control mice. The researchers believe that these sleep disturbances may be related to low serotonin levels, but more research is necessary to determine the mechanism.

The limitations of the study include the fact that the researchers could not disregard the direct effect of the antibiotics on brain function. The researchers suggest that one way to get around this in future studies is to use germ-free mice.

Future studies could also use controlled feeding and the administration of certain microbes to determine the gut microbiota, allowing the team to assess each microorganism’s individual impact on the sleep-wake cycle.

Some research shows that prebiotics, which are nutrients that support a healthy intestinal microbiota, help improve sleep quality in humans. Supplementation with prebiotics may also reduce stress-related sleep disturbances in rats.

Future research will need to test whether these findings hold up in human subjects.