Introduction

Dietary oligosaccharides can impact the gut microbiota and confer tremendous health benefits.

Objectives

The aim of this study was to determine the impact of a novel functional oligosaccharide, neoagarotetraose (NAT), on aging in mice.

Methods

8-month-old C57BL/6J mice as the natural aging mice model were orally administered with NAT for 12 months. The preventive effect of NAT in Alzheimer’s disease (AD) mice was further evaluated. Aging related indicators, neuropathology, gut microbiota and short-chain fatty acids (SCFAs) in cecal contents were analyzed.

Results

NAT treatment extended the lifespan of these mice by up to 33.3 %. Furthermore, these mice showed the improved aging characteristics and decreased injuries in cerebral neurons. Dietary NAT significantly delayed DNA damage in the brain, and inhibited reduction of tight junction protein in the colon. A significant increase at gut bacterial genus level (such as Lactobacillus, Butyricimonas, and Akkermansia) accompanied by increasing concentrations of SCFAs in cecal contents was observed after NAT treatment. Functional profiling of gut microbiota composition indicated that NAT treatment regulated the glucolipid and bile acid-related metabolic pathways. Interestingly, NAT treatment ameliorated cognitive impairment, attenuated amyloid-β (Aβ) and Tau pathology, and regulated the gut microbiota composition and SCFAs receptor-related pathway of Alzheimer’s disease (AD) mice.

Conclusion

NAT mitigated age-associated cerebral injury in mice through gut-brain axis. The findings provide novel evidence for the effect of NAT on anti-aging, and highlight the potential application of NAT as an effective intervention against age-related diseases.

中文翻译：

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膳食新琼脂四糖通过调节微生物群-肠-脑轴延长小鼠寿命并阻止大脑衰老

介绍

膳食低聚糖可以影响肠道微生物群并带来巨大的健康益处。

目标

本研究的目的是确定一种新型功能性寡糖新琼脂四糖 (NAT) 对小鼠衰老的影响。

方法

8月龄C57BL/6J小鼠作为自然衰老小鼠模型，口服NAT，连续12个月。进一步评估了 NAT 对阿尔茨海默病 (AD) 小鼠的预防作用。分析了衰老相关指标、神经病理学、肠道微生物群和盲肠内容物中的短链脂肪酸（SCFA）。

结果

NAT 治疗使这些小鼠的寿命延长了 33.3%。此外，这些小鼠表现出衰老特征的改善和脑神经元损伤的减少。饮食 NAT 显着延缓了大脑中的 DNA 损伤，并抑制了结肠中紧密连接蛋白的减少。NAT 处理后，观察到肠道细菌属水平（如乳杆菌、丁酸单胞菌和阿克曼氏菌）显着增加，同时盲肠内容物中 SCFA 浓度增加。肠道微生物群组成的功能分析表明 NAT 治疗调节糖脂和胆汁酸相关的代谢途径。有趣的是，NAT 治疗可改善阿尔茨海默病 (AD) 小鼠的认知障碍，减弱β淀粉样蛋白 (Aβ) 和 Tau 病理学，并调节肠道微生物群组成和 SCFA 受体相关通路。

结论

NAT 通过肠-脑轴减轻小鼠与年龄相关的脑损伤。这些发现为 NAT 的抗衰老作用提供了新的证据，并强调了 NAT 作为有效干预年龄相关疾病的潜在应用。