Gut microbiome linked to poor sleep via metabolite production

Among the many negative health outcomes that may be driven by changes to our gut microbiome is poor sleep, with recent research uncovering links between it and alterations to the community of bacteria living in our bellies. A new study out of Japan’s University of Tsukuba is shining yet more light on this relationship, describing how depleted diversity of microbes in the gut can led to disrupted sleep in mice.

The research follows similar studies carried out on mice and fruit flies earlier this year, in which scientists found changes to the gut microbiome could lead to high blood pressure and fragmented sleep, as well as early death from sleep deprivation. The latest work carried out at the University of Tsukuba focuses on the role this bacteria plays in affecting sleep via the production of the neurotransmitters serotonin and dopamine.

To investigate this connection, the researchers gave a group of mice strong doses of antibiotics over the course of four weeks. This depleted the diversity of bacteria in their intestines, which led to significant differences in their metabolites compared to a control group of mice fed the same diet.

“We found more than 200 metabolite differences between mouse groups,” says Professor Masashi Yanagisawa, who led the research. “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.”

Metabolites are a byproduct of digested food, and from here the team set out to determine what role the missing ones normally play in healthy mice. They found that the biological pathways most heavily affected by the missing metabolites were the ones that help generate neurotransmitters in the gut, including one that plays a role in creating serotonin from tryptophan, an amino acid found in turkey. The mice were also found to be low in vitamin B6 metabolites, which speed up serotonin and dopamine production.

Next up, the team observed the rodents' sleep performance by using EEGs to monitor their brain activity. Those with the depleted microbiome experienced frequently disrupted sleep/wake cycles, switching between REM and non-REM sleep at a higher rate than the control group, which Yanagisawa suspects is the result of the lack of serotonin.

“We found that microbe depletion eliminated serotonin in the gut, and we know that serotonin levels in the brain can affect sleep/wake cycles,” he says. “Thus, changing which microbes are in the gut by altering diet has the potential to help those who have trouble sleeping.”

The research was published in the journal Scientific Reports.

Source: University of Tsukuba