Probiotics modulate the microbiota-gut-brain axis and improve memory deficits in aged SAMP8 mice
Probiotics modulate the microbiota-gut-brain axis and improve memory deficits in aged SAMP8 mice
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DOI：
10.1016/j.apsb.2019.07.001
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发表时间：
2020-03-01
影响因子：
14.5
通讯作者：
Du, Junrong
中科院分区：
文献类型：
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作者：
Yang, Xueqin;Yu, Dongke;Du, Junrong
ProBiotic-4是由乳酸双歧杆菌、干酪乳杆菌、两歧双歧杆菌和嗜酸乳杆菌组成的益生菌制剂。本研究旨在研究益生素-4对微生物群-肠-脑轴和认知障碍的影响，并利用加速衰老小鼠易感8（SAMP 8）小鼠探索潜在的分子机制。将ProBiotic-4口服给予9个月大的SAMP 8小鼠12周。我们观察到ProBiotic-4显著改善了老年SAMP 8小鼠的记忆缺陷、脑神经元和突触损伤、胶质细胞活化以及粪便和大脑中的微生物群组成。益生菌-4显著减弱了肠屏障和血脑屏障的衰老相关破坏，降低了mRNA和蛋白水平的白细胞介素-6和肿瘤坏死因子-a，降低了血浆和脑脂多糖（LPS）浓度、toll样受体4（TLR 4）表达和脑中核因子-κ B（NF-κ B）核转位。此外，益生菌-4不仅显著降低了γ-H2 AX、8-羟基脱氧鸟苷和视黄酸诱导基因-I（RIG-I）的水平，还消除了大脑中的RIG-I多聚化。这些研究结果表明，用益生菌靶向肠道微生物群可能对衰老中的微生物群-脑轴和认知功能的缺陷具有治疗潜力，其机制与抑制TLR 4和RIG-I介导的NFkB信号通路和炎症反应有关。(C)2020中国药学会、中国医学科学院药物研究所。制作和主办：Elsevier B. V.
ProBiotic-4 is a probiotic preparation composed of Bifidobacterium lactis, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus acidophilus. This study aims to investigate the effects of ProBiotic-4 on the microbiota-gut-brain axis and cognitive deficits, and to explore the underlying molecular mechanism using senescence-accelerated mouse prone 8 (SAMP8) mice. ProBiotic-4 was orally administered to 9-month-old SAMP8 mice for 12 weeks. We observed that ProBiotic-4 significantly improved the memory deficits, cerebral neuronal and synaptic injuries, glial activation, and microbiota composition in the feces and brains of aged SAMP8 mice. ProBiotic-4 substantially attenuated aging-related disruption of the intestinal barrier and blood-brain barrier, decreased interleukin-6 and tumor necrosis factor-a at both mRNA and protein levels, reduced plasma and cerebral lipopolysaccharide (LPS) concentration, toll-like receptor 4 (TLR4) expression, and nuclear factor-kappa B (NF-kappa B) nuclear translocation in the brain. In addition, not only did ProBiotic-4 significantly decreased the levels of gamma-H2AX, 8-hydroxydesoxyguanosine, and retinoic-acid-inducible gene-I ( RIG-I), it also abrogated RIG-I multimerization in the brain. These findings suggest that targeting gut microbiota with probiotics may have a therapeutic potential for the deficits of the microbiotaegutebrain axis and cognitive function in aging, and that its mechanism is associated with inhibition of both TLR4-and RIG-I-mediated NFkB signaling pathway and inflammatory responses. (C) 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.