BACKGROUND Western pattern diets induce neuroinflammation and impair cognitive behavior in humans and animals. Neuroinflammation and cognitive impairment have been associated with microbiota dysbiosis, through the gut-brain axis. Furthermore, microbiota-accessible carbohydrates (MACs) found in dietary fiber are important in shaping the microbial ecosystem and have the potential to improve the gut-brain-axis. However, the effects of MACs on neuroinflammation and cognition in an obese condition have not yet been investigated. The present study aimed to evaluate the effect of MACs on the microbiota-gut-brain axis and cognitive function in obese mice induced by a high-fat and fiber deficient (HF-FD) diet. METHODS C57Bl/6 J male mice were fed with either a control HF-FD or a HF-MAC diet for 15 weeks. Moreover, an additional group was fed with the HF-MAC diet in combination with an antibiotic cocktail (HF-MAC + AB). Following the 15-week treatment, cognitive behavior was investigated; blood, cecum content, colon, and brain samples were collected to determine metabolic parameters, endotoxin, gut microbiota, colon, and brain pathology. RESULTS We report MACs supplementation prevented HF-FD-induced cognitive impairment in nesting building and temporal order memory tests. MACs prevented gut microbiota dysbiosis, including increasing richness, α-diversity and composition shift, especially in Bacteroidetes and its lower taxa. Furthermore, MACs increased colonic mucus thickness, tight junction protein expression, reduced endotoxemia, and decreased colonic and systemic inflammation. In the hippocampus, MACs suppressed HF-FD-induced neuroglia activation and inflammation, improved insulin IRS-pAKT-pGSK3β-pTau synapse signaling, in addition to the synaptic ultrastructure and associated proteins. Furthermore, MACs' effects on improving colon-cognitive parameters were eliminated by wide spectrum antibiotic microbiota ablation. CONCLUSIONS These results suggest that MACs improve cognitive impairments via the gut microbiota-brain axis induced by the consumption of an HF-FD. Supplemental MACs to combat obesity-related gut and brain dysfunction offer a promising approach to prevent neurodegenerative diseases associated with Westernized dietary patterns and obesity.

中文翻译：

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补充微生物群可及的碳水化合物可通过改善饮食诱发的肥胖小鼠的肠道微生物群-脑轴来预防神经炎症和认知能力下降。

背景技术西方模式饮食在人和动物中诱发神经炎症并损害认知行为。神经炎症和认知障碍已通过肠脑轴与微生物群失调相关。此外，在膳食纤维中发现的微生物可及的碳水化合物（MACs）在塑造微生物生态系统方面很重要，并具有改善肠脑轴的潜力。然而，尚未研究在肥胖状况下MAC对神经炎症和认知的影响。本研究旨在评估MACs对高脂和纤维缺乏（HF-FD）饮食诱导的肥胖小鼠微生物群-肠脑轴和认知功能的影响。方法用对照HF-FD或HF-MAC饮食喂养C57Bl / 6 J雄性小鼠15周。此外，另一组喂食了HF-MAC饮食和抗生素鸡尾酒（HF-MAC + AB）。治疗15周后，调查了认知行为；收集血液，盲肠含量，结肠和脑样本，以确定代谢参数，内毒素，肠道菌群，结肠和脑病理。结果我们报告说，在巢式构建和时间顺序记忆测试中，MACs的添加阻止了HF-FD引起的认知障碍。MACs预防了肠道微生物群的营养不良，包括增加了其丰富度，α-多样性和成分转移，尤其是在拟杆菌和其较低的分类群中。此外，MAC可增加结肠粘液厚度，紧密连接蛋白表达，减少内毒素血症以及减少结肠和全身炎症。在海马体中 除突触超微结构和相关蛋白外，MAC还抑制了HF-FD诱导的神经胶质细胞活化和炎症，改善了胰岛素IRS-pAKT-pGSK3β-pTau突触信号传导。此外，广谱抗生素菌群消融消除了MACs对改善结肠认知参数的影响。结论这些结果表明，MACs通过食用HF-FD引起的肠道菌群-脑轴改善了认知障碍。对抗肥胖相关的肠道和脑功能障碍的补充MAC提供了一种有前途的方法来预防与西餐饮食模式和肥胖相关的神经退行性疾病。广谱抗生素菌群消融消除了对改善结肠认知参数的影响。结论这些结果表明，MACs通过食用HF-FD引起的肠道菌群-脑轴改善了认知障碍。对抗肥胖相关肠道和脑功能障碍的补充MAC提供了一种有前途的方法，可以预防与西餐饮食模式和肥胖相关的神经退行性疾病。广谱抗生素菌群消融消除了对改善结肠认知参数的影响。结论这些结果表明，MACs通过食用HF-FD引起的肠道菌群-脑轴改善了认知障碍。对抗肥胖相关的肠道和脑功能障碍的补充MAC提供了一种有前途的方法来预防与西餐饮食模式和肥胖相关的神经退行性疾病。