食品科学 ›› 2025, Vol. 46 ›› Issue (5): 182-193.doi: 10.7506/spkx1002-6630-20240818-130

• 营养卫生 • 上一篇    下一篇

后生元调节肠道微生态及减少脑内β-淀粉样蛋白沉积改善阿尔茨海默病大鼠的认知障碍

肖灵,唐琳琳,宋晓妍,张艺华,韩雪梅,吕厚姣,梁武,王艳萍,耿伟涛,贾龙刚   

  1. (1.天津科技大学食品科学与工程学院,天津市食品质量与健康重点实验室,天津 300457;2.天津创源生物技术有限公司,天津市食用益生菌重点实验室,天津 300301)
  • 出版日期:2025-03-15 发布日期:2025-02-07
  • 基金资助:
    天津市食品质量与健康重点实验室开放基金资助项目(TJS202301)

Postbiotics Regulate Intestinal Microbiota and Reduce Amyloid β-Protein Deposition in the Brain, Thereby Ameliorating Cognitive Impairment in Rats with Alzheimer’s Disease

XIAO Ling, TANG Linlin, SONG Xiaoyan, ZHANG Yihua, HAN Xuemei, LÜ Houjiao, LIANG Wu, WANG Yanping, GENG Weitao, JIA Longgang   

  1. (1. Tianjin Key Laboratory of Food Quality and Health, College of Food Science and Engineering, Tianjin University of Science and Technology, Tianjin 300457, China; 2. Tianjin Key Laboratory of Edible Probiotics, Tianjin InnoOrigin Biological Biotechnology Co., Ltd., Tianjin 300301, China)
  • Online:2025-03-15 Published:2025-02-07

摘要: 为探究3 种不同剂量的后生元对D-半乳糖联合AlCl3诱导的阿尔茨海默病(Alzheimer’s disease,AD)大鼠记忆认知能力的影响,以SPF级Wistar大鼠为实验对象,随机分为空白对照组,AD模型组,阳性药物盐酸多奈哌齐对照组,后生元动物双歧杆菌乳亚种IOBL07低、高剂量组(108、109 CFU/kg),后生元植物乳植杆菌IOB602低、高剂量组(108、109 CFU/kg)和后生元副干酪乳酪杆菌IOB413低、高剂量组(108、109 CFU/kg)。除空白组腹腔注射生理盐水、灌胃生理盐水外,其余各组均腹腔注射D-半乳糖,同时灌胃AlCl3,连续造模13 周,在造模药物注射并灌胃结束1 h后,干预组分别灌胃盐酸多奈哌齐和3 种不同剂量的后生元,空白组和模型组灌胃等量的生理盐水。采用Morris水迷宫测试各组大鼠学习记忆能力,并测定大鼠海马中β-淀粉样蛋白(amyloid β-protein,Aβ)的含量及其荧光强度,小肠组织病理形态和肠道菌群的变化,粪便、血清及海马中脂多糖(lipopolysaccharide,LPS)水平和炎症因子信号通路Toll样受体4(Toll-like receptor 4,TLR4)/NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)/髓样分化因子88(myeloid differentiation factor 88,MyD88)相对表达量。结果表明,3 种不同剂量的后生元均能够显著提升AD大鼠的学习记忆能力,并显著降低海马中Aβ的含量,降低粪便、血清及海马中LPS水平和炎症因子信号通路TLR4/NLRP3/MyD88的相对表达量。肠道菌群分析结果显示,后生元的干预可以调节AD大鼠肠道微生物群的结构和组成,与AD组大鼠相比,各后生元干预组肠道优势菌Firmicutes和肠道有益菌Ruminococcaceae相对丰度增加,肠道有害菌Muribaculaceae相对丰度降低。因此,后生元具有明显改善AD大鼠记忆认知障碍的作用,且后生元植物乳植杆菌IOB602高剂量组的干预效果最佳,其机制可能与改善肠道微生物群的结构组成和降低脑组织炎症因子信号通路的相对表达量有关。

关键词: 阿尔茨海默病, 后生元, 认知障碍, 肠道菌群, 炎症因子

Abstract: This study aimed to investigate the impact of three postbiotics at different doses on cognitive function in a rat model of Alzheimer’s disease (AD) induced by D-galactose combined with AlCl3. Specific pathogen-free (SPF) Wistar rats were randomly divided into nine groups: control (Ctrl), AD model, positive drug (donepezil hydrochloride), low-dose (108 CFU/kg) and high-dose (109 CFU/kg) Bifidobacterium animalis spp. lactis IOBL07, Lactiplantibacillus plantarum IOB602 and L. paracasei IOB413. The Ctrl group was intraperitoneally and orally administered with normal saline, while all other experimental groups were subjected to intraperitoneal injection of D-galactose and oral gavage of AlCl3. The model induction period lasted for 13 consecutive weeks. At 1 h following the last injection and oral gavage, the intervention groups were orally administered with donepezil hydrochloride or postbiotics, whereas the Ctrl and AD groups were given an equivalent volume of normal saline. The Morris water maze was used to assess the learning and memory capacities of the rats in each group. Additionally, the content and immunofluorescence intensity of amyloid β-protein (Aβ) in hippocampal tissues were determined. Histopathological changes in the small intestine were examined along with changes in the intestinal microbiota. The levels of lipopolysaccharide (LPS) in feces, serum, and hippocampal tissues were determined as well as the relative mRNA transcription levels of toll-like receptor 4 (TLR4), NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and myeloid differentiation factor 88 (MyD88) in brain tissues. The results showed that all three postbiotics could significantly improve the learning and memory capacities of AD rats, significantly reduce the content of Aβ in hippocampal tissues, and decrease the LPS levels in feces, serum, and hippocampal tissues and the relative mRNA transcription levels of TLR4, NLRP3 and MyD88 in brain tissues. Intervention with the postbiotics regulated the structure and composition of the intestinal microbiota. In the postbiotic intervention groups, the relative abundance of the predominant intestinal bacteria, Firmicutes, and the beneficial species, Ruminococcaceae increased, the relative abundance of the potential harmful intestinal bacteria, Muribaculaceae, decreased compared with the AD model group. Thus, the postbiotics IOBL07, IOB602, and IOB413 have significant efficacy in ameliorating memory and cognitive deficits in AD rats, the most pronounced effect being observed with high-dose IOB602. The underlying mechanisms might be associated with regulating the structure and composition of the gut microbiota and down-regulating the relative mRNA transcription levels of TLR4, NLRP3 and MyD88 in brain tissues.

Key words: Alzheimer’s disease, postbiotics, cognitive impairment, gut microbiota, inflammatory factors

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