How the Gut Microbiome Controls Sleep and Circadian Rhythm

Summary: Normal sleep patterns in mice depend on gut bacteria that support the production of key neurotransmitters—most notably serotonin.

Source: University of Tsukuba

Gut microbes influence sleep: an overview of the mouse study

As autumn and winter gatherings approach, many people wonder how food affects sleep. Researchers led by Professor Masashi Yanagisawa at the University of Tsukuba focused on a crucial intermediary in that relationship: the gut microbiota. In a controlled mouse study, the team demonstrated that eliminating intestinal microbes changes the intestinal metabolite profile and produces measurable changes in sleep architecture and brain electrical activity.

Study design and methods

The experimental protocol was straightforward. Adult C57BL/6 male mice received a broad-spectrum antibiotic cocktail for four weeks to deplete gut microbes. These antibiotic-treated, microbiota-depleted mice were compared with control mice on the same diet but with an intact microbiome. The researchers analyzed cecal contents to profile metabolites—small molecules that represent digestion and microbial activity—and recorded sleep using electroencephalogram (EEG) and electromyogram (EMG) monitoring to evaluate sleep/wake cycles and EEG power spectra.

Key metabolite changes

Metabolome profiling revealed more than 200 differences between the two groups. Approximately 60 metabolites present in controls were absent from microbiota-depleted mice, while other metabolites showed altered concentrations. Pathway-level analysis highlighted pronounced disruptions in metabolic routes involved in neurotransmitter synthesis. The tryptophan–serotonin pathway, in particular, was nearly shut down: treated mice accumulated higher levels of tryptophan but had almost no serotonin in the gut.

The study also identified deficiencies in vitamin B6–related metabolites in microbiota-depleted mice. Vitamin B6 plays a supporting role in synthesizing neurotransmitters such as serotonin and dopamine, so its reduction likely contributes to altered neurotransmitter availability.

This shows a woman clutching her belly
The team also found that the mice were deficient in vitamin B6 metabolites, which accelerate production of the neurotransmitters serotonin and dopamine. Credit: Emily Frost

Sleep and EEG findings

EEG and EMG recordings showed that microbiota depletion changed sleep timing and structure. Compared with controls, antibiotic-treated mice spent less time in non-rapid eye movement sleep (NREMS) during the light phase—when mice typically rest—and more time in both NREMS and rapid eye movement sleep (REMS) during the dark phase—when mice are usually active. The number of REM episodes increased during both light and dark periods, and the number of NREMS episodes rose during the day. These changes reflect more frequent transitions between sleep and wake states and more rapid switching between NREMS and REMS. Additionally, theta power density during REMS was reduced in microbiota-depleted mice during the light phase.

Interpretation and implications

Professor Yanagisawa and colleagues propose that the loss of gut-derived serotonin and reduced vitamin B6 metabolites are central to the observed sleep disturbances. Because serotonin influences brain circuits that regulate sleep and wakefulness, depleting the microbes that help produce serotonin from dietary tryptophan appears to alter sleep architecture. While the precise mechanisms linking intestinal metabolites to brain function and EEG changes remain to be fully mapped, the findings suggest that gut microbiota composition—and by extension diet—can affect sleep regulation.

These results highlight a potential route for dietary or microbial interventions to improve sleep in people with sleep difficulties, though translation from mouse models to humans requires further research.


About this sleep research news

Source: University of Tsukuba
Contact: Press Office – University of Tsukuba
Image: Emily Frost / University of Tsukuba

Original Research: Open access. “Gut microbiota depletion by chronic antibiotic treatment alters the sleep/wake architecture and sleep EEG power spectra in mice” by Yukino Ogawa, Chika Miyoshi, Nozomu Obana, Kaho Yajima, Noriko Hotta-Hirashima, Aya Ikkyu, Satomi Kanno, Tomoyoshi Soga, Shinji Fukuda & Masashi Yanagisawa. Scientific Reports.


Abstract

Gut microbiota depletion by chronic antibiotic treatment alters the sleep/wake architecture and sleep EEG power spectra in mice

Dysbiosis of the gut microbiota influences physiological processes, including brain function, by changing intestinal metabolism. In this study, male C57BL/6 mice received broad-spectrum antibiotics for four weeks to deplete gut microbes. Metabolome profiling of cecal contents revealed significant changes in amino acid and vitamin metabolism relevant to neurotransmission, including depletion of serotonin and vitamin B6–related metabolites in microbiota-depleted mice. Sleep analysis using EEG and EMG showed that these mice spent less time in NREMS during the light (rest) phase and more time in NREMS and REMS during the dark (active) phase. The number of REMS episodes increased across both phases, with frequent transitions from NREMS to REMS, and theta power during REMS was reduced in the light phase. These results indicate that the gut microbiota can shape sleep/wake architecture by altering intestinal neurotransmitter balance.