Zhang Zeng, Peng Qiannan, Huo Dongxue, Jiang Shuaiming, Ma Chenchen, Chang Haibo, Chen Kaining, Li Congfa, Pan Yonggui, Zhang Jiachao
Key Laboratory of Food Nutrition and Functional Food of Hainan Province, College of Food Science and Engineering, Hainan University, Haikou, China.
Institute of Marine Science and Technology, Shandong University, Qingdao, China.
Front Cell Dev Biol. 2021 May 20;9:678190. doi: 10.3389/fcell.2021.678190. eCollection 2021.
Melatonin has been widely used as a "probiotic agent" capable of producing strong neurotransmitter secretion regulatory effects, and the microbiota-gut-brain axis-related studies have also highlighted the role of the gut microbiota in neuromodulation. In the present study, a zebrafish neural hyperactivity model was established using caffeine induction to explore the regulatory effects of melatonin and probiotic on neurotransmitter secretion disorder in zebrafish. Disorders of brain neurotransmitter secretion (dopamine, γ-aminobutyric acid, and 5-hydroxytryptamine) caused by caffeine were improved after interference treatment with melatonin or probiotic. Shotgun metagenomic sequencing demonstrated that the melatonin-treated zebrafish gradually restored their normal intestinal microbiota and metabolic pathways. Germ-free (GF) zebrafish were used to verify the essential role of intestinal microbes in the regulation of neurotransmitter secretion. The results of the neurotransmitter and short-chain fatty acid determination revealed that the effect on the zebrafish in the GF group could not achieve that on the zebrafish in the melatonin group after adding the same dose of melatonin. The present research revealed the potential mode of action of melatonin through the microbiota-gut-brain axis to regulate the disruption of neurotransmitter secretion, supporting the future development of psychotropic drugs targeting the intestinal microbiota.
褪黑素已被广泛用作一种能够产生强大神经递质分泌调节作用的“益生菌剂”，并且微生物群-肠-脑轴相关研究也突出了肠道微生物群在神经调节中的作用。在本研究中，使用咖啡因诱导建立斑马鱼神经活动亢进模型，以探究褪黑素和益生菌对斑马鱼神经递质分泌紊乱的调节作用。用褪黑素或益生菌进行干预处理后，由咖啡因引起的脑内神经递质（多巴胺、γ-氨基丁酸和5-羟色胺）分泌紊乱得到改善。鸟枪法宏基因组测序表明，经褪黑素处理的斑马鱼逐渐恢复了其正常的肠道微生物群和代谢途径。使用无菌（GF）斑马鱼来验证肠道微生物在神经递质分泌调节中的重要作用。神经递质和短链脂肪酸测定结果显示，在添加相同剂量褪黑素后，GF组对斑马鱼的影响无法达到褪黑素组对斑马鱼的影响。本研究揭示了褪黑素通过微生物群-肠-脑轴调节神经递质分泌紊乱的潜在作用模式，为未来针对肠道微生物群的精神药物开发提供了支持。
