College of Food Science & Technology, Nanjing Agricultural University, Nanjing 210095, China.
Institute of Vegetable, Gansu Academy of Agricultural Sciences, Lanzhou 730070, China.
Food Funct. 2023 Feb 21;14(4):1909-1928. doi: 10.1039/d2fo04014j.
Large preclinical evidence suggested that colitis was one of the risk factors for depression and probiotics were effective therapeutic agents to prevent the disease. The effect of Fmb14 on colitis-related depression-like behavior and its possible mechanisms were investigated. One week of DSS exposure led to the following changes in male C57BL/6N mice: a reduction in the movement distance from 2218 to 1299 cm, time in central areas from 23.6 s to 11.5 s, and time in the bright box from 217 s to 103 s, which were restored to 1816 cm, 18.4 s, and 181 s, respectively, with preadministration of Fmb14 for 8 weeks. All improvements provided by Fmb14 indicated a remarkable protective effect on depression-like behavior. Fmb14 first worked to repair intestinal barrier damage and the inflammatory response in the colon through ZO1 and Ocln enhancement and IL-1β, NF-κB and IL-6 reduction, respectively. Second, dysbiosis of the gut microbiota was modulated by Fmb14, including reduction of (18.9% to 5.4%), (0.6% to 0.1%) and (0.32% to 0.03%). Fmb14 supplementation ameliorates the brain inflammatory response IL-18 and NF-κB reduction and improves the blood-brain barrier increased levels of ZO1 and Ocln. Moreover, brain activity was facilitated by an increase in BDNF and dopamine and the downregulation of GABA in the Fmb14 group. As a consequence of the modulatory effect on the dysfunction of neurotransmitters and neuroinflammation, Fmb14 prevents neurodegeneration by inhibiting neuronal apoptosis and Nissl edema. In addition, the correlation analysis further demonstrated the preventative effect of Fmb14 on depression-like behavior through the microbiota-gut-brain axis. Together, these findings demonstrated the important role of Fmb14 in biological signal transduction over the microbiota-gut-brain axis to improve mood disorders.
大量的临床前证据表明，结肠炎是导致抑郁的一个风险因素，而益生菌是预防这种疾病的有效治疗药物。本研究旨在探讨 Fmb14 对结肠炎相关的抑郁样行为的影响及其可能的机制。在雄性 C57BL/6N 小鼠中，DSS 暴露一周会导致以下变化：运动距离从 2218cm 减少到 1299cm，中央区域时间从 23.6s 减少到 11.5s，明亮箱时间从 217s 减少到 103s，而用 Fmb14 预处理 8 周后，这些变化分别恢复到 1816cm、18.4s 和 181s。Fmb14 提供的所有改善都表明对抑郁样行为具有显著的保护作用。Fmb14 首先通过增强 ZO1 和 Ocln 来修复肠道屏障损伤和结肠炎症反应，降低 IL-1β、NF-κB 和 IL-6，从而发挥作用。其次，Fmb14 调节肠道微生物群的失调，包括减少 （从 18.9%减少到 5.4%）、 （从 0.6%减少到 0.1%）和 （从 0.32%减少到 0.03%）。Fmb14 补充剂可改善大脑炎症反应 降低 IL-18 和 NF-κB，改善血脑屏障 增加 ZO1 和 Ocln 的水平。此外，Fmb14 组通过增加 BDNF 和多巴胺并下调 GABA 来促进大脑活动。由于对神经递质和神经炎症功能障碍的调节作用，Fmb14 通过抑制神经元凋亡和尼氏水肿来预防神经退行性变。此外，相关性分析进一步证明了 Fmb14 通过微生物群-肠道-大脑轴对抑郁样行为的预防作用。总之，这些发现表明 Fmb14 在通过微生物群-肠道-大脑轴进行生物信号转导方面对改善情绪障碍具有重要作用。
