Data Sheet 1_Lacticaseibacillus rhamnosus CBT LR5 with skim milk alleviates scopolamine-induced cognitive impairment in mice.docx

IntroductionEmerging evidence highlights the gut-brain axis as a pivotal pathway linking gastrointestinal health with cognitive function, particularly in neurodegenerative conditions such as Alzheimer’s disease (AD).
MethodsThis study investigated the cognitive-enhancing effects of the probiotic strain Lacticaseibacillus rhamnosus CBT LR5 (LR5), alone or in combination with skim milk, in a mouse model of scopolamine-induced cognitive impairment. The cognitive functions were evaluated using the novel object recognition test (NOR) and the passive avoidance test (PAT).
ResultsThe results demonstrated that the oral administration of LR5, especially when combined with skim milk, significantly ameliorated scopolamine-induced cognitive deficits. Mechanistically, treatment with LR5 combined with skim milk restored the diversity and composition of the gut microbiota increased the abundance of beneficial genera, such as Muribaculaceae and enhanced intestinal barrier integrity by increasing the expression of tight junction proteins, including claudin-1, occludin, and zonula occludens-1. Additionally, this combination reduced systemic inflammation by lowering serum TNF-α and PGE2 levels and promoted increased expression of BDNF by activating the CREB-BDNF-TrkB signaling pathway in hippocampal and cortical tissues. Furthermore, correlation analyses revealed significant associations between specific gut bacterial genera, such as Lacticaseibacillus, Turicibacter, Cryptobacteroides, Ruminococcus, and Muribaculaceae, and cognitive or inflammatory biomarkers.
DiscussionCollectively, these findings suggest that the synergistic effects of L. rhamnosus CBT LR5 combined with skim milk may represent an effective dietary intervention for cognitive enhancement, potentially through gut microbiota modulation, improved barrier integrity, reduced inflammation, and enhanced neurotrophic signaling.

引言 越来越多的研究证据表明，肠-脑轴（gut-brain axis）是联结胃肠道健康与认知功能的核心通路，在阿尔茨海默病（Alzheimer’s disease, AD）等神经退行性疾病中发挥着关键作用。
方法 本研究以东莨菪碱诱导的认知障碍小鼠模型为对象，探究了鼠李糖乳杆菌（Lacticaseibacillus rhamnosus）CBT LR5（LR5）单独灌胃或与脱脂乳联合使用的认知增强效应。采用新物体识别实验（novel object recognition test, NOR）与避暗实验（passive avoidance test, PAT）对小鼠认知功能进行评价。
结果 结果表明，灌胃LR5，尤其是与脱脂乳联合使用时，可显著改善东莨菪碱诱导的认知功能缺陷。机制层面，LR5与脱脂乳联合处理可恢复肠道菌群（gut microbiota）的多样性与组成，提升Muribaculaceae科（Muribaculaceae）等有益菌属的丰度；同时通过上调闭合蛋白-1（claudin-1）、紧密连接蛋白Occludin（occludin）以及闭锁小带蛋白-1（zonula occludens-1）等紧密连接蛋白的表达，增强肠道屏障完整性。此外，该联合疗法可通过降低血清肿瘤坏死因子-α（TNF-α）与前列腺素E2（PGE2）水平减轻全身炎症反应，并通过激活海马与皮层组织中的cAMP反应元件结合蛋白-脑源性神经营养因子-酪氨酸激酶受体B（CREB-BDNF-TrkB）信号通路，促进脑源性神经营养因子（BDNF）的表达上调。相关性分析进一步揭示，特定肠道细菌属如乳杆菌属（Lacticaseibacillus）、图里杆菌属（Turicibacter）、隐杆菌属（Cryptobacteroides）、瘤胃球菌属（Ruminococcus）以及Muribaculaceae科（Muribaculaceae）与认知或炎症生物标志物存在显著关联。
讨论 综上，本研究结果提示，鼠李糖乳杆菌CBT LR5与脱脂乳联合使用的协同效应有望成为一种有效的认知增强饮食干预策略，其潜在机制可能涉及肠道菌群调控、肠道屏障功能改善、全身炎症反应减轻以及神经营养信号通路增强。