Zhao Lina, Li Dongyao, Chitrakar Bimal, Li Chen, Zhang Na, Zhang Shaogang, Wang Xinyu, Wang Miaoshu, Tian Hongtao, Luo Yunbo
College of Food Science and Technology, Hebei Agricultural University, Baoding, Hebei 071000, China.
Hebei Technology Innovation Center of Probiotic Functional Dairy Product, Baoding, Hebei 071000, China.
Food Funct. 2023 Apr 3;14(7):3304-3318. doi: 10.1039/d2fo03708d.
The prevention, mitigation and treatment of depression has become a global issue that needs to be solved urgently. Sayram Ketteki, a traditional natural fermented yoghurt from the region with the world's fourth highest life expectancy, has been known as the "longevity secret", whose longevity and anti-depression factors are speculated to come from its rich microorganisms. Therefore, for the first time, we systematically studied in depth the microbes of Sayram Ketteki, screened a new edible probiotic strain, R6-3, and explored its anti-depression effect in chronic unpredictable mild stress (CUMS)-induced depression in mice. It is encouraging that R6-3 was significantly superior to the classic anti-depressant drug, fluoxetine, in the performance of promoting sucrose preference test (SPT) behavior by 18% ( < 0.001), lowering the serum CORT content by 5.6% ( < 0.05), accelerating the brain-derived neurotrophic factor (BDNF) level by 5.9% ( < 0.01), increasing the serum IL-10 concentration by 2.3% ( < 0.05), up-regulating the expression of BDNF and phosphorylated-ERK by 74% ( < 0.01) and 45% ( < 0.001), respectively, and facilitating the secretion of fecal short-chain fatty acids (SCFAs), including -butyric, -valeric, and isovaleric acid by 47% ( < 0.01), 42% ( < 0.05) and 38% ( < 0.05), respectively. Through the microbiota-gut-brain axis, R6-3 promoted the secretion of intestinal SCFAs through regulation of the composition and function of the gut microbiota, and activated the production of the monoamine neurotransmitter, renewed the level of brain neurotrophic factor, and suppressed the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis by adjusting the hippocampal BDNF/TrkB/ERK/CREB signaling pathway, thereby improving the immune and oxidative stress status, protecting hippocampal tissue from damage, maintaining a healthy weight and preventing CUMS-induced depressive behavior in mice. It has great prospects for the development of natural functional foods, the prevention and treatment of depression and in innovative microecological preparations.
抑郁症的预防、缓解和治疗已成为一个亟待解决的全球性问题。赛里木开提克是一种来自世界预期寿命排名第四地区的传统天然发酵酸奶，被誉为“长寿秘诀”，其长寿和抗抑郁因子据推测来自其丰富的微生物群。因此，我们首次对赛里木开提克的微生物群进行了系统深入的研究，筛选出一种新的可食用益生菌菌株R6-3，并探讨了其在慢性不可预测轻度应激（CUMS）诱导的小鼠抑郁症中的抗抑郁作用。令人鼓舞的是，在促进蔗糖偏好试验（SPT）行为方面，R6-3比经典抗抑郁药物氟西汀表现更为显著，提高了18%（<0.001），血清皮质酮（CORT）含量降低了5.6%（<0.05），脑源性神经营养因子（BDNF）水平提高了5.9%（<0.01），血清白细胞介素-10（IL-10）浓度增加了2.3%（<0.05），BDNF和磷酸化细胞外信号调节激酶（p-ERK）的表达分别上调了74%（<0.01）和45%（<0.001），粪便短链脂肪酸（SCFAs），包括丁酸、戊酸和异戊酸的分泌分别增加了47%（<0.01）、42%（<0.05）和38%（<0.05）。通过微生物-肠道-脑轴，R6-3通过调节肠道微生物群的组成和功能促进肠道SCFAs的分泌，激活单胺类神经递质的产生，恢复脑神经营养因子水平，并通过调节海马体BDNF/酪氨酸激酶受体B（TrkB）/ERK/环磷腺苷效应元件结合蛋白（CREB）信号通路抑制下丘脑-垂体-肾上腺（HPA）轴的亢进，从而改善免疫和氧化应激状态，保护海马组织免受损伤，维持健康体重，预防CUMS诱导的小鼠抑郁行为。它在天然功能性食品的开发、抑郁症的预防和治疗以及创新微生态制剂方面具有广阔的前景。
