A recent study published in Engineering has identified a potential new approach to managing sleep disorders. The research, led by a team of scientists from Jiangnan University and other institutions, focuses on the role of S-adenosylmethionine (SAM)-producing probiotics in regulating sleep and circadian rhythms.

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Insomnia is a common sleep disorder that affects a significant portion of the global population. Current first-line medications for sleep disorders often have suboptimal effectiveness, highlighting the need for novel therapeutic strategies.

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In this study, the researchers first conducted a cross-sectional analysis and found that serum SAM levels were significantly reduced in insomnia patients. This discovery suggests that SAM could serve as a potential biomarker and therapeutic target for sleep disorders.

Sleep deprivation

The team then screened 60 gut strains and identified Lactobacillus helveticus CCFM1320, a high-SAM-producing probiotic. In a mouse model of sleep deprivation, treatment with CCFM1320 reversed neurobehavioral abnormalities, such as improved recognition and memory of new objects, reduced hyperactivity, and enhanced spatial exploration ability. Mechanistically, CCFM1320 enhanced the methylation of N-acetylserotonin, a precursor of melatonin synthesis, which normalized the expression of downstream circadian rhythm genes.

To further evaluate the clinical efficacy of CCFM1320, the researchers conducted a four-week placebo-controlled clinical trial involving 60 volunteers with insomnia. The results showed that CCFM1320 significantly improved sleep quality in patients with sleep disorders. Participants had reduced Pittsburgh sleep quality index (PSQI) scores, lower serum cortisol levels, and a decreased prevalence of pathogenic species in the gut. Additionally, probiotic treatment elevated the abundance of SAM synthesis and metabolism-related enzyme genes in the gut microbiome.

Gut microbiome

The study also explored the impact of CCFM1320 on the gut microbiota of insomnia patients. Although the overall gut microbiota diversity did not change, the intervention affected the composition and abundance of core microbiota species. Probiotic treatment reduced the number of potentially pathogenic species and increased the abundance of some beneficial bacteria.

However, the study has some limitations. The efficiency of gut microbiota-derived SAM supplementation to the circulatory system and brain requires further validation. Also, the differences in the effects of probiotics on sleep quality indices and hormone levels between the human trial and animal studies need to be further investigated.

Promising strategy

Overall, this research presents a promising probiotic-based strategy for managing sleep disorders, offering a potential non-pharmacological treatment alternative. Further studies are needed to fully understand the mechanisms and optimize the use of these probiotics in clinical practice.

The paper “Regulation of Sleep and Circadian Rhythms by S-Adenosylmethionine-Producing Probiotics,” authored by Peijun Tian, Yuming Lan, Zhiying Jin, Feng Hang, Xuhua Mao, Xing Jin, Gang Wang, Wei Chen. Full text of the open access paper: https://doi.org/10.1016/j.eng.2024.12.025