Researchers in Japan, at the University of Tsukuba, have just published an incredibly interesting study on the bacterial microbiome and sleep.[i] While it was conducted in mice, it undoubtedly has implications for humans as well. As you know from my previous posts on the subject (see here and here as just two examples), the link between sleep and the microbiome has already been established, but the exact mechanisms of action have not been fully elucidated.
In this experiment, the researchers gave mice a cocktail of strong antibiotics for 4 weeks, decimating their microbiomes. Bearing in mind that when you digest, food is broken down by your body and your microbes into metabolites, the scientists compared these metabolites in the experimental group to those in normal controls. All mice ate the same diets. As you might expect, there were major differences: more than 200 metabolites differed, with 60 missing altogether.
The question then became – what do these differing metabolites actually do in the body? This is where this research gets really interesting: they found that the antibiotics most affected biological pathways involved in making neurotransmitters. One of the most dramatic examples: the tryptophan-serotonin pathway was almost entirely non-functional. The treated mice had more tryptophan than the controls, but almost no serotonin. Tryptophan is an amino acid that is the precursor to serotonin and without normal gut bacteria, the mice could not make the conversion. Another discovery: the treated mice were deficient in B6 metabolites, which are crucial in the production of serotonin, as well as the catecholamines, including and dopamine, adrenaline and noradrenaline. What’s more, as you’ve read in previous posts of mine (like here for example), the gut bacteria themselves follow circadian rhythms: “…disrupting these oscillations perturbs the host circadian clocks…” So basically, the mouse – or the person – gets with a double whammy.
(All I could think of as I read this were the number of children with autism and related disorders that I have worked with over the years who were given antibiotics at birth or in the first 2 years of life…like my own son. How common are anxiety and sleep issues in this population?!)
The researchers also analyzed sleep in the animals. At night, the pineal gland in the brain converts serotonin to melatonin, which helps induce sleep. Again, as you’d expect, there were significant differences: mice are nocturnal, but at night – when they should have been most active – the treated mice had way more REM and non-REM sleep than the controls; and too, they had less non-REM sleep during the day when they should have been sleeping. Basically, the treated mice reversed their whole sleep/wake cycles: “…the gut microbiota is suggested to affect the sleep/wake architecture by altering the intestinal balance of neurotransmitters.”
The paper concludes by saying that, “This study has revealed the relationship between the gut microbiota and sleep/wake regulation, indicating that changes to the intestinal microbiota have the potential to improve sleep-related problems such as daytime sleepiness and insomnia. Notably, some prebiotics have already been shown to improve subjective sleep quality in humans and stress-induced sleep disruption in rats.” Says the lead researcher of this study, “We found that microbe depletion eliminated serotonin in the gut, and we know that serotonin levels in the brain can affect sleep/wake cycles. Thus, changing which microbes are in the gut by altering diet has the potential to help those who have trouble sleeping.”[ii]
[i] Ogawa, Y., et al. (2020) Gut microbiota depletion by chronic antibiotic treatment alters the sleep/wake architecture and sleep EEG power spectra in mice. Scientific Reports. doi.org/10.1038/s41598-020-76562-9.