,Probiotics modulate the microbiota-gut-brain axis and improve memory deficits in aged SAMP8 mice

• 作 者: Xueqin Yang Dongke Yu Li Xue Hui Li Junrong Du
• 机 构: Department of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Educati
• 出 处: 药学学报（英文版）
• 发表日期: 2020年3期
• 关键词: Microbiota-gut-brain axis Cognitive decline TLR4 RIG-Ⅰ NF-κB Probiotics SAMP8 mi

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-α at both mRNA and protein levels,reduced plasma and cerebral lipopolysaccharide (LPS) concentration,toll-like receptor 4 (TLR4) expression,and nuclear factor-κB (NF-κB) nuclear translocation in the brain.In addition,not only did ProBiotic-4 significantly decreased the levels of γ-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 microbiota-gut-brain axis and cognitive function in aging,and that its mechanism is associated with inhibition of both TLR4-and RIG-Ⅰ-mediated NF-κB signaling pathway and inflammatory responses.