Inulin Ameliorates Cognitive Dysfunction in Type Ⅱ Diabetic Mice by Regulating Intestinal Flora
This study aimed to explore the effects of inulin on cognitive function of type 2 diabetes(T2D)mice.The T2D model was constructed by high-fat diet combined with streptozotocin.Forty-five mice were ran-domly divided into 3 groups with 15 mice in each group,and each mouse was kept in a single cage.Mice in normal group(Con group)were fed with a normal diet,those in model group(T2D group)were fed a high-fat diet,and those in inulin intervention group(DI group)were fed the high-fat diet supplemented with 10%inulin.The feeding experiment was carried out for 8 weeks after adaptive feeding for 1 week.The results showed that inulin significantly alleviated the weight loss in T2D mice(starting from week 4,P<0.05),sig-nificantly reduced the fasting blood glucose(starting from week 4,P<0.05),significantly decreased serum low-density lipoprotein-cholesterol(LDL-C)and total cholesterol(TC)levels(P<0.05),and significantly increased serum high-density lipoprotein-cholesterol(HDL-C)level(P<0.05).In addition,inulin improved the cognitive behavioral and hippocampal neuronal damage in T2D mice,significantly or extremely significant-ly un-regulated the mRNA and protein relative expression levels of nuclear factor E2 related factor 2(Nrf2)and heme oxygenase-1(HO-1)(P<0.05 or P<0.01),and extremely significantly down-regulated the protein relative expression level of high mobility group box protein 1(HMGB1)(P<0.01).Inulin significantly de-creased the contents of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in serum and hippocam-pus,and interleukin-6(IL-6)in hippocampus(P<0.05).Inulin significantly decreased the content of malond-ialdehyde(MDA)in hippocampus(P<0.05),and extremely significantly increased the activities of superox-ide dismutase(SOD)and glutathione peroxidase(GSH-Px)in hippocampus(P<0.01).The enrichment of Lactobacillus,Weissella,Dubosiella,Kurthia and unclassified_f_erysipelotrichaceae in T2D mice,and resul-ted in an extremely significantly decrease in the contents of acetic acid,butyric acid,isovaleric acid,valeric acid,hexanoic acid and total short-chain fatty acids(SCFAs)in the colon contents(P<0.01);the addition of inulin enriched Bifidobacterium,Faecalibacterium and Ileobacterium in T2D mice,and significantly or ex-tremely significantly increased the contents of acetic acid,butyric acid,isovaleric acid,valeric acid andhexano-ic acid in the colon contents(P<0.05 or P<0.01).In conclusion,inulin can affect the structure of the colon microbiota and the production of its metabolites SCFAs,improve T2D mice'weight and FBG,regulate blood lipid level,serum and hippocampal inflammatory factor contents,regulate Nrf2,HO-1 and HMGB1 expression and improve oxidative stress-related indicators in the hippocampus,and it play an important role in reducing hippocampal neuronal damage and cognitive behaviors.[Chinese Journal of Animal Nutrition,2024,36(11):7305-7319]
inulinT2D cognitive dysfunctionoxidative stress and inflammationSCFAscolonic microbes