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寡糖和类黄酮介导的益生元干预措施治疗与肠道菌群失调相关的认知衰退

Oligosaccharide and Flavanoid Mediated Prebiotic Interventions to Treat Gut Dysbiosis Associated Cognitive Decline.

作者信息

Sarkar Suparna Roy, Mazumder Papiya Mitra, Banerjee Sugato

机构信息

Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India.

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Kolkata, West Bengal, India.

出版信息

J Neuroimmune Pharmacol. 2022 Jun;17(1-2):94-110. doi: 10.1007/s11481-021-10041-4. Epub 2022 Jan 19.

Abstract

Oligosaccharides are potential prebiotic which maintains gut microbiota and improves gut health. The association of gut and brain is named as gut-brain-axis. Gut dysbiosis disrupts gut-brain-axis and effectively contributes to psychiatric disorders. In the present study, Xylo-oligosaccharide (XOS) and Quercetin were used as therapeutic interventions against gut dysbiosis mediated cognitive decline. Gut dysbiosis was established in mice through administration of Ampicillin Sodium, orally for 14 days. XOS and quercetin were administered separately or in combination along with antibiotic. Gene expression studies using mice faecal samples showed both XOS and quercetin could revive Lactobacillus, Bifidobacterium, Firmicutes and Clostridium which were reduced due to antibiotic treatment. FITC-dextran concentration in serum revealed XOS and quercetin protected intestinal barrier integrity against antibiotic associated damage. This was verified by histopathological studies showing restored intestinal architecture. Moreover, intestinal inflammation which increased after antibiotic treated animals was reduced upon XOS and quercetin treatment. Behavioural studies demonstrated that gut dysbiosis reduced fear conditioning, spatial and recognition memory which were reversed upon XOS and quercetin treatment. XOS and quercetin also reduced inflammation and acetylcholine esterase which were heightened in antibiotic treated animal brain. They also reduced oxidative stress, pro-inflammatory cytokines and chemokines and protected hippocampal neurons. In conclusion, XOS and quercetin effectively reduced antibiotic associated gut dysbiosis and prevented gut dysbiosis associated cognitive decline in mice.

摘要

低聚糖是一种潜在的益生元,可维持肠道微生物群并改善肠道健康。肠道与大脑的关联被称为肠-脑轴。肠道菌群失调会破坏肠-脑轴,并有效地导致精神疾病。在本研究中,木寡糖(XOS)和槲皮素被用作针对肠道菌群失调介导的认知衰退的治疗干预措施。通过口服氨苄西林钠14天在小鼠中建立肠道菌群失调。XOS和槲皮素与抗生素分开或联合给药。使用小鼠粪便样本进行的基因表达研究表明,XOS和槲皮素都可以使因抗生素治疗而减少的乳酸杆菌、双歧杆菌、厚壁菌门和梭菌恢复活力。血清中的异硫氰酸荧光素-葡聚糖浓度表明,XOS和槲皮素可保护肠道屏障完整性免受抗生素相关损伤。组织病理学研究显示肠道结构恢复,证实了这一点。此外,XOS和槲皮素治疗后,抗生素处理动物后增加的肠道炎症有所减轻。行为学研究表明,肠道菌群失调会降低恐惧条件反射、空间和识别记忆,而XOS和槲皮素治疗后这些症状会得到逆转。XOS和槲皮素还降低了抗生素处理动物大脑中升高的炎症和乙酰胆碱酯酶。它们还减少了氧化应激、促炎细胞因子和趋化因子,并保护了海马神经元。总之,XOS和槲皮素有效地减少了抗生素相关的肠道菌群失调,并预防了小鼠中与肠道菌群失调相关的认知衰退。

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