Good-sleep diet: effects on sleep mediated by gut-to-brain direct interactions in modified diets

Titos I, Juginović A, Vaccaro A, et al. A gut-secreted peptide suppresses arousability from sleep. Cell 2023;1867:1382–1397.e21. doi: 10.1016/j.cell.2023.02.022.

To ensure sleep is deep and restorative, external stimuli have to be suppressed. Across species, ‘good sleep’ is influenced by multiple genes. External factors, like diet, have been recognised to impact on sleep quality.

Titos et al identified a gut signalling pathway that suppresses arousability in flies and mice models. Using increased vibrations’ intensity, Titos et al identified arousable phenotypes of flies. Neuropeptide CCHamide1 (CCHa1) and its receptor were then recognised as leading to hyperarousability and poor sleep when suppressed. Depletion of CCHa1, which is present in the nervous system and enteroendocrine cells, in the gut alone was enough to increase arousability (but not other aspects of sleep). By activating enteroendocrine cells, the authors showed suppression of arousability, but if depleted of CCHa1, the effect was lost. Using calcium-dependent nuclear import of LexA system that identifies active cells in natural environment, increased activity in CCHa1 cells was shown following sustained (24 hours vs 6 hours) high-protein diet, but not in sugar and fat in eu-caloric diet experiments. Similarly, mice fed with high-protein diet were harder to wake up and spent more time in the rapid eye movement phase of sleep (deeper) than control mice. Flies were more arousable when CCHa1 receptor was suppressed in a specific subpopulation of protocerebral anterior medial (PAM) dopaminergic cells, while their eating behaviour was not affected. When exposed to high-protein diets, this specific PAM cluster was activated, suggesting direct gut-to-brain signalling. Despite its limitations, this study improves the understanding about how diet affects sleep and demonstrates the need for future studies on interactions between diet, gut and brain.

Extrachromosomal DNA in oesophageal adenocarcinoma: when, why, how?

Luebeck J, Ng A, Galipeau P, et al. Extrachromosomal DNA in the cancerous transformation of Barrett’s oesophagus. …