Rescue of social deficits by early-life melatonin supplementation through modulation of gut microbiota in a murine model of autism
文献类型： 外文期刊
作者： Liu, Wei 5 ; Zhang, Di 1 ; Liu, Xia 1 ; Cui, Yi 3 ; Zhang, Yuhan 1 ; Xiang, Guo 1 ; Yu, Meng 1 ; Wang, Xianshu 5 ; Qiu, Bin 5 ; Li, Xin-gang 1 ;
作者机构： 1.Shandong Univ, Qilu Hosp, Dept Neurosurg, Jinan 250012, Peoples R China
2.Jinan Microecol Biomed Shandong Lab, Jinan 250000, Peoples R China
3.Shandong Univ, Qilu Hosp, Dept Crit Care Med, Jinan 250012, Peoples R China
4.Shandong Univ, Inst Brain & Brain Inspired Sci, Jinan 250012, Peoples R China
5.Shandong Acad Agr Sci, Insititute Food & Nutr Sci & Technol, Jinan 250100, Peoples R China
6.Shandong Univ, Qilu Hosp, Dept Neurosurg, 107 Wenhuaxi Rd, Jinan 250012, Peoples R China
7.Shandong Acad Agr Sci, nstitute Food & Nutr Sci & Technol, 23788 Gongyebei Rd, Jinan 250100, Peoples R China
关键词： Melatonin; Gut microbiota; Akkermansia; Ventral tegmental area
期刊名称：BIOMEDICINE & PHARMACOTHERAPY （ 影响因子：7.419； 五年影响因子：6.581 ）
ISSN： 0753-3322
年卷期： 2022 年 156 卷
页码：
收录情况： SCI
摘要： Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a rapidly increasing global prevalence. Early unstable and immature microbiota are often observed in ASD patients, resulting in neurobehavioral dysfunction. Since the establishment of stable gut microbiota in early life falls into the same critical time window as neurodevelopment, manipulations of the gut microbiota during early life could become a promising strategy for ASD. Melatonin is an endogenous hormone and can restore gut microbial dysbiosis under various disease conditions. Here, we explored the effects of melatonin supplementation during early life on the gut microbiota of the offspring and the subsequent impact on ASD-associated behaviors. Using the valproic acid (VPA) - induced mouse model of autism, we found that melatonin supplementation during late gestation and early postnatal development rescued the social deficits of the offspring. In addition, melatonin restored gut microbial dysbiosis in the VPA-exposed offspring, which was characterized by the significant upregulation of Akkermansia spp. Furthermore, supplementation of Akkermansia spp. alleviated the social deficits induced by VPA exposure via activating the dopaminergic neurons in the ventral tegmental area. These findings discover a novel mechanism underlying the gut microbiota regulation of social behaviors and provide the biological basis for developing gut microbiota-based therapeutics for ASD
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