Background:The intestinal microbiota and its metabolites, particularly short-chain fatty acids (SCFAs), have been implicated in immune function, host metabolism, and even behavior. Objective:This study was performed to investigate whether probiotic administration influences levels of intestinal microbiota and their metabolites in a fashion that may attenuate brain changes in a mouse model of Alzheimer’s disease (AD). Methods:C57BL/6 wild-type (WT) mice were compared to AppNL-G-Fmice. The animals were treated with either vehicle or probiotic (VSL#3) for 8 weeks. Fecal microbiome analysis along with Aβ, GFAP, Iba-1, c-Fos, and Ki-67 immunohistochemistry was done. SCFAs were analyzed in serum and brains using UPLC-MS/MS. Results:Probiotic (VSL#3) supplementation for 2 months resulted in altered microbiota in both WT and AppNL-G-Fmice. An increase in serum SCFAs acetate, butyrate, and lactate were found in both genotypes following VSL#3 treatment. Propionate and isobutyrate were only increased in AppNL-G-Fmice. Surprisingly, VSL#3 only increased lactate and acetate in brains of AppNL-G-Fmice. No significant differences were observed between vehicle and VSL#3 fed AppNL-G-Fhippocampal immunore activities of Aβ, GFAP, Iba-1, and Ki-67. However, hippocampal c-Fos staining increased in VSL#3 fed AppNL-G-Fmice. Conclusion:These data demonstrate intestinal dysbiosis in the AppNL-G-Fmouse model of AD. Probiotic VSL#3 feeding altered both serum and brain levels of lactate and acetate in AppNL-G-Fmice correlating with increased expression of the neuronal activity marker, c-Fos.

中文翻译：

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补充益生菌对阿尔茨海默病 AppNL-GF 小鼠模型中短链脂肪酸的影响。

背景：肠道微生物群及其代谢物，特别是短链脂肪酸（SCFA），与免疫功能、宿主代谢甚至行为有关。目的：本研究旨在调查益生菌的施用是否会影响肠道微生物群及其代谢物的水平，从而减轻阿尔茨海默病 (AD) 小鼠模型的大脑变化。方法：将 C57BL/6 野生型 (WT) 小鼠与 AppNL-G-F 小鼠进行比较。这些动物用载体或益生菌 (VSL#3) 治疗 8 周。进行了粪便微生物组分析以及 Aβ、GFAP、Iba-1、c-Fos 和 Ki-67 免疫组织化学分析。使用 UPLC-MS/MS 分析血清和脑中的 SCFA。结果：补充益生菌 (VSL#3) 2 个月导致 WT 和 AppNL-G-F 小鼠的微生物群发生改变。VSL#3 治疗后，两种基因型的血清 SCFA 乙酸盐、丁酸盐和乳酸盐均有所增加。丙酸盐和异丁酸盐仅在 AppNL-G-Fmice 中增加。令人惊讶的是，VSL#3 仅增加 AppNL-G-Fmice 大脑中的乳酸和乙酸盐。在赋形剂和 VSL#3 饲喂 AppNL-G-Fhippocampal 的 Aβ、GFAP、Iba-1 和 Ki-67 免疫活性之间没有观察到显着差异。然而，喂食 VSL#3 的 AppNL-G-F 小鼠中海马 c-Fos 染色增加。结论：这些数据表明 AD 的 AppNL-G-Fmouse 模型中肠道菌群失调。益生菌 VSL#3 喂养改变了 AppNL-G-Fmice 血清和大脑中乳酸和乙酸的水平，与神经元活动标记物 c-Fos 表达增加相关。