Department of Food and Nutrition, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
Neurobiota Research Center, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
Benef Microbes. 2021 Nov 16;12(6):541-551. doi: 10.3920/BM2020.0109. Epub 2021 Sep 13.
The gut microbiota communicates with the brain through microbiota-gut-brain (MGB) and hypothalamus-pituitary-adrenal (HPA) axes and other pathways. Excessive expression of interleukin (IL)-6 is closely associated with the occurrence of the psychiatric disorders depression and dementia. Therefore, to understand whether IL-6 expression-suppressing probiotics could alleviate psychiatric disorders, we isolated IL-6 expression-inhibiting (formerly ) NK112 from the human faecal bacteria strain collection (Neurobiota Research Center, Seoul, Korea) and examined its therapeutic effect for the depression and cognitive impairment in mice. C57 BL/6J mice with depression and cognitive impairment were prepared by exposure to K1. Oral gavage of NK112 significantly alleviated K1-induced anxious, depressive, and memory-impaired behaviours in the elevated plus maze, tail-suspension and Y-maze tasks, IL-1β, IL-6, and tumour necrosis factor (TNF)-α expression, and nuclear factor kappa beta (NF-κB) activation in the hippocampus, while K1-suppressed brain-derived neurotrophic factor (BDNF) expression increased. Treatment with NK112 also improved K1-induced myeloperoxidase activity, IL-6 and TNF-α expression, and NF-κB activation in the colon and reduced K1-induced population in the gut microbiota. Heat-killed NK112 and its lysate supernatant, and precipitate fractions also improved anxiety/depression, cognitive impairment, and colitis in mice. In conclusion, NK112, even if heat-killed or lysed, alleviated K1 stress-induced colitis, anxiety/depression, and cognitive impairment by suppressing IL-6, TNF-α, and BDNF expression through the regulation of gut microbiota and NF-κB activation.
肠道微生物群通过微生物群-肠道-脑（MGB）和下丘脑-垂体-肾上腺（HPA）轴以及其他途径与大脑进行交流。白细胞介素（IL）-6 的过度表达与精神障碍抑郁症和痴呆症的发生密切相关。因此，为了了解是否可以通过抑制白细胞介素（IL）-6 表达的益生菌来缓解精神障碍，我们从人类粪便细菌株库（韩国首尔神经生物研究中心）中分离出了抑制 IL-6 表达的（以前称为）NK112，并检查了其对抑郁和认知障碍的治疗效果。在小鼠中。通过暴露于 K1 来制备具有抑郁和认知障碍的 C57BL/6J 小鼠。NK112 的口服灌胃显著缓解了 K1 在高架十字迷宫、悬尾和 Y 迷宫任务中引起的焦虑、抑郁和记忆障碍，减轻了海马中 IL-1β、IL-6 和肿瘤坏死因子（TNF）-α 的表达和核因子 kappa beta（NF-κB）的激活，同时 K1 抑制了脑源性神经营养因子（BDNF）的表达。NK112 的治疗还改善了 K1 引起的髓过氧化物酶活性、IL-6 和 TNF-α 的表达以及 NF-κB 的激活，并减少了肠道微生物群中 K1 诱导的种群。热处理的 NK112 及其溶解物上清液和沉淀物也改善了小鼠的焦虑/抑郁、认知障碍和结肠炎。总之，NK112，即使热失活或溶解，也通过调节肠道微生物群和 NF-κB 激活来抑制 IL-6、TNF-α 和 BDNF 的表达，从而缓解 K1 应激引起的结肠炎、焦虑/抑郁和认知障碍。
