Gut microbiota regulates host melatonin production through epithelial cell MyD88
Bingnan Liu,
Lijuan Fan,
Youxia Wang,
Hao Wang,
Yuqi Yan,
Shuai Chen,
Ifen Hung,
Chunxue Liu,
Hong Wei,
Liangpeng Ge,
Wenkai Ren
Affiliations
Bingnan Liu
State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
Lijuan Fan
State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
Youxia Wang
State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
Hao Wang
State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
Yuqi Yan
Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, China
Shuai Chen
Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China
Ifen Hung
Anyou Biotechnology Group Co. LTD, Taicang, China
Chunxue Liu
Anyou Biotechnology Group Co. LTD, Taicang, China
Hong Wei
State Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Technology, Key Laboratory of Agricultural Animal Genetics, Breeding, and Reproduction of the Ministry of Education & Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, China
Liangpeng Ge
National Center of Technology Innovation for Pigs, Chongqing, China
Wenkai Ren
State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
ABSTRACTMelatonin has various physiological effects, such as the maintenance of circadian rhythms, anti-inflammatory functions, and regulation of intestinal barriers. The regulatory functions of melatonin in gut microbiota remodeling have also been well clarified; however, the role of gut microbiota in regulating host melatonin production remains poorly understood. To address this, we studied the contribution of gut microbiota to host melatonin production using gut microbiota-perturbed models. We demonstrated that antibiotic-treated and germ-free mice possessed diminished melatonin levels in the serum and elevated melatonin levels in the colon. The influence of the intestinal microbiota on host melatonin production was further confirmed by fecal microbiota transplantation. Notably, Lactobacillus reuteri (L. R) and Escherichia coli (E. coli) recapitulated the effects of gut microbiota on host melatonin production. Mechanistically, L. R and E. coli activated the TLR2/4/MyD88/NF-κB signaling pathway to promote expression of arylalkylamine N-acetyltransferase (AANAT, a rate-limiting enzyme for melatonin production), and MyD88 deficiency in colonic epithelial cells abolished the influence of intestinal microbiota on colonic melatonin production. Collectively, we revealed a specific underlying mechanism of gut microbiota to modulate host melatonin production, which might provide novel therapeutic ideas for melatonin-related diseases.
