Yu Pan,1,* Yan Yuan,1,* Juan Yang,2,* Zhu Qing Feng,1 Xue Yin Tang,1 Yi Jiang,1 Gui Ming Hu,1 Dong Li Luo,1 Yang Jiang,1 Jiang Chuan Dong3 

1Department of Geriatrics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 2Department of Integrated of Chinese and Western Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Oncology Treatment Center of Traditional Chinese Medicine, Affiliated Cancer Hospital of Chongqing University, Chongqing, 400900, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jiang Chuan Dong, Email dongjiangchuan2023@163.com

Abstract: Disruption of circadian rhythms and the condition of frailty are believed to be interrelated. Various manifestations of sleep disturbances, including insomnia, disrupted sleep-wake cycles, and alterations in sleep timing, are considered integral components of circadian rhythm disruption, which are also observed in individuals with frailty. Extensive research has established a connection between gut microbiota and both frailty and circadian rhythm disruption. However, prior studies have predominantly focused on investigating isolated links between gut microbiota and its metabolites with either frailty or circadian rhythm disruption, often neglecting the significant role that gut microbiota and its metabolites may play in the bidirectional relationship between circadian rhythms and frailty. Consequently, we propose the hypothesis that circadian rhythm disruption may induce frailty by altering the composition and structure of gut microbiota metabolites, and conversely, frailty may influence circadian rhythm disruption through similar mechanisms. The aim of our hypothesis is to emphasize the important role of gut microbiota metabolites in the bidirectional communication between circadian disruption and frailty and to speculate on the relevant mechanisms by which gut microbiota metabolites mediate the bidirectional communication between circadian disruption and frailty, rather than being solely related to frailty or circadian disorders.

Keywords: circadian rhythm, frailty, gut microbiota metabolites