No Sleep ’till Gut Balance

Gut Health

Whether it’s a belly full of turkey from the recent Thanksgiving holiday or just a really big meal, we have all experienced the sedative effects that come along with the feasting. While there are a host of potential factors that span the relationship between food and sleep, the microbiota of the gut is an area that is getting more of the recognition that it rightfully deserves. As such, a team of investigators from the University of Tsukuba has recently published their detailed findings in mice that revealed the extent to which bacteria can change the environment and contents of the intestines, which ultimately impacts behaviors like sleep.

Results from the new study were published recently in Scientific Reports through an article titled, “Gut microbiota depletion by chronic antibiotic treatment alters the sleep/wake architecture and sleep EEG power spectra in mice.”

The research team set up very simple yet straightforward experiments that gave a group of mice a powerful cocktail of antibiotics for four weeks, which depleted them of intestinal microorganisms. They then compared intestinal contents between these mice and control mice who had the same diet. The scientists found significant differences between metabolites in the microbiota-depleted mice and the control mice.

“We found more than 200 metabolite differences between mouse groups,” noted senior study investigator Masashi Yanagisawa, MD, PhD, professor at the University of Tsukuba and UT Southwestern Medical Center. “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.”

Next, Yanagisawa and his colleagues set out to determine what these metabolites normally do. Using metabolome set enrichment analysis, they found that the biological pathways most affected by the antibiotic treatment were those involved in making neurotransmitters, the molecules that cells in the brain use to communicate with each other. For example, the tryptophan-serotonin pathway was almost totally shut down; the microbiota-depleted mice had more tryptophan than controls but almost zero serotonin. This shows that without important gut microbes, the mice could not make any serotonin from the tryptophan they were eating. The team also found that the mice were deficient in vitamin B6 metabolites, which accelerate the production of the neurotransmitters serotonin and dopamine.

“We examined the effects of the gut microbiota on sleep/wake regulation. C57BL/6 male mice were treated with broad-spectrum antibiotics for four weeks to deplete their gut microbiota,” the authors wrote. “Metabolome profiling of cecal contents in antibiotic-induced microbiota-depleted (AIMD) and control mice showed significant variations in the metabolism of amino acids and vitamins related to neurotransmission, including depletion of serotonin and vitamin B6, in the AIMD mice. Sleep analysis based on electroencephalogram and electromyogram recordings revealed that AIMD mice spent significantly less time in non-rapid eye movement sleep (NREMS) during the light phase while spending more time in NREMS and rapid eye movement sleep (REMS) during the dark phase.”

Yanagisawa and his team also analyzed how the mice slept by looking at brain activity in EEGs. They found that compared with the control mice, the microbiota-depleted mice had more REM and non-REM sleep at night—when mice are supposed to be active—and less non-REM sleep during the day—when mice should be mostly sleeping. The number of REM sleep episodes was higher both during the day and at night, whereas the number of non-REM episodes was higher during the day. In other words, the microbiota-depleted mice switched between sleep/wake stages more frequently than the controls.

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



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