Shorter sleep time relates to lower human defensin 5 secretion and compositional disturbance of the intestinal microbiota accompanied by decreased short-chain fatty acid production

ABSTRACT

Sleep is essential for our health. Short sleep is known to increase disease risks via imbalance of intestinal microbiota, dysbiosis. However, mechanisms by which short sleep induces dysbiosis remain unknown. Small intestinal Paneth cell regulates the intestinal microbiota by secreting antimicrobial peptides including α-defensin, human defensin 5 (HD5). Disruption of circadian rhythm mediating sleep-wake cycle induces Paneth cell failure. We aim to clarify effects of short sleep on HD5 secretion and the intestinal microbiota. Fecal samples and self-reported sleep time were obtained from 35 healthy middle-aged Japanese (41 to 60-year-old). Shorter sleep time was associated with lower fecal HD5 concentration (r = 0.354, p = 0.037), lower centered log ratio (CLR)-transformed abundance of short-chain fatty acid (SCFA) producers in the intestinal microbiota such as [Ruminococcus] gnavus group (r = 0.504, p = 0.002) and Butyricicoccus (r = 0.484, p = 0.003), and lower fecal SCFA concentration. Furthermore, fecal HD5 positively correlated with the abundance of these genera and SCFA concentration. These findings suggest that short sleep relates to disturbance of the intestinal microbiota via decreased HD5 secretion.

KEYWORDS:

• Short sleep
• α-defensin
• Paneth cell
• Intestinal microbiota
• Short-chain fatty acid
• Sleep disorder

Author contribution

Conceptualization: YS, TA, AT, and Kiminori N. Data curation: YS, RY, YY, SU, Koshi N, EO, AI, TN, AT, and Kiminori N. Formal analysis: YS, YY, and Kiminori N. Funding acquisition: TA, AT, and Kiminori N. Investigation: YS and Kiminori N. Methodology: YS and Kiminori N. Project administration: AT and Kiminori N. Resources: YS and Kiminori N. Supervision: TA and Kiminori N. Validation: YS and Kiminori N. Visualization: YS and Kiminori N. Writing-original draft: YS. Writing-review & editing: TA, AT, and Kiminori N. All authors read, revised, and approved the final draft.

Acknowledgments

The authors gratefully acknowledge all volunteers who participated in our study, municipal government officers of Suttu town, staff members of Suttu municipal clinic, and other people who cooperated with the DOSANCO Health Study. The authors also acknowledge experimental supports from Ms. Aiko Kuroishi.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author, Kiminori N. The data are not publicly available due to their containing information that could compromise the privacy of research participants.

Ethics approval

This study was approved by the Ethical Committee of the Faculty of Medicine (15–002, 15–045), Hokkaido University. Written informed consent was obtained from all participants.

Additional information

Funding

This study was supported by the Japan Society for the Promotion of Science [22K16009 to YS, 18H02788 to TA, 26670322 to AT, and 17K11661 to Kiminori N]; Japan Science and Technology Agency [JPMJCE 1301 to TA, AT, and Kiminori N, JPMJPF2108 to AT and Kiminori N]; Ministry of Agriculture, Forestry and Fisheries, Japan [14538261 to AT]; the Japan Foundation for Aging and Health [2015-58-2 to SU]; and the Mitsubishi Foundation [10492 to AT].