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

Yu Shimizu; Ryodai Yamamura; Yuki Yokoi; Tokiyoshi Ayabe; Shigekazu Ukawa; Koshi Nakamura; Emiko Okada; Akihiro Imae; Takafumi Nakagawa; Akiko Tamakoshi; Kiminori Nakamura

doi:10.1080/19490976.2023.2190306

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

Gut Microbes. 2023 Jan-Dec;15(1):2190306. doi: 10.1080/19490976.2023.2190306.

Authors

Affiliations

¹ Department of Cell Biological Science, Faculty of Advanced Life Science, Hokkaido University, Hokkaido, Japan.
² Division of Biomedical Oncology, Institute for Genetic Medicine, Hokkaido University, Hokkaido, Japan.
³ Department of Social Welfare Science and Clinical Psychology, Osaka Metropolitan University Graduate School of Human Life and Ecology, Osaka, Japan.
⁴ Department of Public Health and Hygiene, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
⁵ Department of Nutritional Epidemiology and Shokuiku, National Institute of Biomedical Innovation, Health and Nutrition, Tokyo, Japan.
⁶ Suttu Municipal Clinic, Hokkaido, Japan.
⁷ The Centre for Family Medicine, Hokkaido, Japan.
⁸ Department of Public Health, Faculty of Medicine, Hokkaido University, Hokkaido, Japan.

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: Intestinal microbiota; Paneth cell; Short sleep; Short-chain fatty acid; Sleep disorder; α-defensin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Defensins
Dysbiosis / metabolism
Fatty Acids, Volatile
Gastrointestinal Microbiome*
Humans
Middle Aged
Sleep

Substances

Fatty Acids, Volatile
Defensins

Grants and 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].