Regulation of Sleep and Circadian Rhythms by S-Adenosylmethionine-Producing Probiotics

Peijun Tian , Yuming Lan , Zhiying Jin , Feng Hang , Xuhua Mao , Xing Jin , Gang Wang , Wei Chen

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Engineering ›› DOI: 10.1016/j.eng.2024.12.025

Regulation of Sleep and Circadian Rhythms by S-Adenosylmethionine-Producing Probiotics

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Abstract

Current first-line medications for sleep disorders often overlap with antidepressants, yet their effectiveness remains suboptimal, highlighting the urgent need for novel therapeutic strategies based on new mechanisms. Our study initially identified a significant reduction in serum S-adenosylmethionine (SAM) levels in insomnia patients through a cross-sectional analysis, suggesting SAM as a potential biomarker and therapeutic target for sleep disorders. We then screened 60 gut strains across seven species and identified a high-SAM-producing probiotic, Lactobacillus helveticus CCFM1320, which improved cognitive and memory impairments caused by sleep deprivation in mice. Mechanistically, CCFM1320 enhances the methylation of N-acetylserotonin, a precursor of melatonin synthesis, normalizing the expression of downstream circadian rhythm genes. A subsequent four-week placebo-controlled clinical trial demonstrated that CCFM1320 significantly improved sleep quality in patients with sleep disorders, as evidenced by reduced Pittsburgh sleep quality index (PSQI) scores, lower serum cortisol levels, and decreased prevalence of pathogenic species in the gut. Probiotic treatment also elevated the abundance of SAM synthesis and metabolism-related enzyme genes in the gut microbiome, likely due to the introduction of high-SAM-producing probiotics and subsequent SAM accumulation. This study presents a promising probiotic-based strategy for managing sleep disorders, offering a potential non-pharmacological treatment alternative.

Keywords

Lactobacillus / S-adenosylmethionine / Sleep / Circadian rhythm / Melatonin

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Peijun Tian, Yuming Lan, Zhiying Jin, Feng Hang, Xuhua Mao, Xing Jin, Gang Wang, Wei Chen. Regulation of Sleep and Circadian Rhythms by S-Adenosylmethionine-Producing Probiotics. Engineering DOI:10.1016/j.eng.2024.12.025

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CRediT authorship contribution statement

Peijun Tian: Writing – review & editing, Writing – original draft, Funding acquisition, Conceptualization. Yuming Lan: Visualization, Investigation. Zhiying Jin: Visualization, Investigation. Feng Hang: Resources. Xuhua Mao: Methodology. Xing Jin: Investigation. Gang Wang: Methodology, Funding acquisition. Wei Chen: Writing – review & editing, Supervision, Resources, Funding acquisition, Conceptualization.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (32394051 and 32201988), National Key Research and Development Program of China (2023YFC2506004), the Fundamental Research Funds for the Central Universities (JUSRP123047), Special Fund for Science and Technology Program of Jiangsu Province (BM2022019), and the Program of Collaborative Innovation Centre of Food Safety and Quality Control in Jiangsu Province.

Compliance with ethics guidelines

Peijun Tian, Yuming Lan, Zhiying Jin, Feng Hang, Xuhua Mao, Xing Jin, Gang Wang, and Wei Chen declare that they have no conflict of interest or financial conflicts to disclose.

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