Administration of Exogenous Melatonin Improves the Diurnal Rhythms of the Gut Microbiota in Mice Fed a High-Fat Diet
Jie Yin,
Yuying Li,
Hui Han,
Jie Ma,
Gang Liu,
Xin Wu,
Xingguo Huang,
Rejun Fang,
Kenkichi Baba,
Peng Bin,
Guoqiang Zhu,
Wenkai Ren,
Bie Tan,
Gianluca Tosini,
Xi He,
Tiejun Li,
Yulong Yin
Affiliations
Jie Yin
College of Animal Science and Technology, Hunan Co-Innovation Center of Animal Production Safety, Hunan Agricultural University, Changsha, China
Yuying Li
Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Chinese Academy of Sciences, Changsha, Hunan, China
Hui Han
Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Chinese Academy of Sciences, Changsha, Hunan, China
Jie Ma
College of Animal Science and Technology, Hunan Co-Innovation Center of Animal Production Safety, Hunan Agricultural University, Changsha, China
Gang Liu
College of Animal Science and Technology, Hunan Co-Innovation Center of Animal Production Safety, Hunan Agricultural University, Changsha, China
Xin Wu
Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Chinese Academy of Sciences, Changsha, Hunan, China
Xingguo Huang
College of Animal Science and Technology, Hunan Co-Innovation Center of Animal Production Safety, Hunan Agricultural University, Changsha, China
Rejun Fang
College of Animal Science and Technology, Hunan Co-Innovation Center of Animal Production Safety, Hunan Agricultural University, Changsha, China
Kenkichi Baba
Department of Pharmacology and Toxicology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, Georgia, USA
Peng Bin
College of Veterinary Medicine, Yangzhou University, Yangzhou, China
Guoqiang Zhu
College of Veterinary Medicine, Yangzhou University, Yangzhou, China
Wenkai Ren
Guangdong Provincial Key Laboratory of Animal Nutrition Control, Institute of Subtropical Animal Nutrition and Feed, College of Animal Science, South China Agricultural University, Guangzhou, China
Bie Tan
College of Animal Science and Technology, Hunan Co-Innovation Center of Animal Production Safety, Hunan Agricultural University, Changsha, China
Gianluca Tosini
Department of Pharmacology and Toxicology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, Georgia, USA
Xi He
College of Animal Science and Technology, Hunan Co-Innovation Center of Animal Production Safety, Hunan Agricultural University, Changsha, China
Tiejun Li
Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Chinese Academy of Sciences, Changsha, Hunan, China
Yulong Yin
College of Animal Science and Technology, Hunan Co-Innovation Center of Animal Production Safety, Hunan Agricultural University, Changsha, China
ABSTRACT Melatonin, a circadian hormone, has been reported to improve host lipid metabolism by reprogramming the gut microbiota, which also exhibits rhythmicity in a light/dark cycle. However, the effect of the administration of exogenous melatonin on the diurnal variation in the gut microbiota in mice fed a high-fat diet (HFD) is unclear. Here, we further confirmed the antiobesogenic effect of melatonin on mice fed an HFD for 2 weeks. Samples were collected every 4 h within a 24-h period, and diurnal rhythms of clock gene expression (Clock, Cry1, Cry2, Per1, and Per2) and serum lipid indexes varied with diurnal time. Notably, Clock and triglycerides (TG) showed a marked rhythm in the control in melatonin-treated mice but not in the HFD-fed mice. The rhythmicity of these parameters was similar between the control and melatonin-treated HFD-fed mice compared with that in the HFD group, indicating an improvement caused by melatonin in the diurnal clock of host metabolism in HFD-fed mice. Moreover, 16S rRNA gene sequencing showed that most microbes exhibited daily rhythmicity, and the trends were different for different groups and at different time points. We also identified several specific microbes that correlated with the circadian clock genes and serum lipid indexes, which might indicate the potential mechanism of action of melatonin in HFD-fed mice. In addition, effects of melatonin exposure during daytime or nighttime were compared, but a nonsignificant difference was noticed in response to HFD-induced lipid dysmetabolism. Interestingly, the responses of microbiota-transplanted mice to HFD feeding also varied at different transplantation times (8:00 and 16:00) and with different microbiota donors. In summary, the daily oscillations in the expression of circadian clock genes, serum lipid indexes, and the gut microbiota appeared to be driven by short-term feeding of an HFD, while administration of exogenous melatonin improved the composition and diurnal rhythmicity of some specific gut microbiota in HFD-fed mice. IMPORTANCE The gut microbiota is strongly shaped by a high-fat diet, and obese humans and animals are characterized by low gut microbial diversity and impaired gut microbiota compositions. Comprehensive data on mammalian gut metagenomes shows gut microbiota exhibit circadian rhythms, which is disturbed by a high-fat diet. On the other hand, melatonin is a natural and ubiquitous molecule showing multiple mechanisms of regulating the circadian clock and lipid metabolism, while the role of melatonin in the regulation of the diurnal patterns of gut microbial structure and function in obese animals is not yet known. This study delineates an intricate picture of melatonin-gut microbiota circadian rhythms and may provide insight for obesity intervention.
