Sleep disorders associated with lifestyle changes and unhealthy habits are major public health concerns. Our previous study showed that Bifidobacterium adolescentis SBT2786 has a potent sleep-promoting effect on fruit flies. Fruit flies share many similarities with mammals, making them suitable model organisms for studying sleep. Thus, in the present study, we conducted a randomized, double-blind, placebo-controlled clinical trial to test whether SBT2786 has sleep-enhancing effects in humans. In this study, 61 participants in the SBT2786 group and 65 participants in the placebo group were analyzed. The results showed that SBT2786 increased sleep time; however, it predominantly increased light sleep and did not improve subjective sleep quality. Interestingly, mood improvement was observed. A subgroup analysis was conducted on participants with high stress levels, and results showed that these participants experienced an increase in sleep duration and an improvement in sleepiness upon waking up and reported feeling well-rested during the day. We concluded that SBT2786 may improve sleep quality, particularly in individuals experiencing high levels of stress, and that SBT2786 can be used as a dietary supplement to improve sleep and mood.

We previously identified the sleep-promoting bacterium Bifidobacterium adolescentis SBT2786; however, its molecular mechanism remains unknown. In Drosophila melanogaster, tissue-/region-specific RNA interference (RNAi) targeted the gut-brain neuropeptide CCHamide-1 (CCHa1) and the CCHa1 receptor (CCHa1R). The increase in SBT2786-induced early-night sleep was abolished by systemic CCHa1 and pan-neuronal CCHa1R knockdown. This phenotype persisted after enteroendocrine cell-specific CCHa1 knockdown, suggesting that it is not fully explained by gut enteroendocrine cell-derived CCHa1 alone. Region-specific RNAi revealed that CCHa1R is required in the ellipsoid body (EB), not the fan-shaped body and tested dopaminergic populations. Ring-driver mapping implicated EB ring neuron circuits, including R3-enriched populations, in the SBT2786 effect: CCHa1R knockdown with the 189 years driver abolished the effect, whereas knockdown with drivers labeling R2/R4m populations did not. These findings show that SBT2786-induced early-night sleep requires CCHa1-CCHa1R signaling and EB ring neuron circuits, and is not fully explained by enteroendocrine cell-derived CCHa1.