Department of Translational Medicine (DIMET) & Center for Translational Research on Autoimmune and Allergic Disease (CAAD), University of Piemonte Orientale, Novara, Italy.
Department of Health Science (DSS) & Center for Translational Research on Autoimmune and Allergic Disease (CAAD), University of Piemonte Orientale, Novara, Italy.
PLoS One. 2022 Aug 24;17(8):e0273036. doi: 10.1371/journal.pone.0273036. eCollection 2022.
The key role played by host-microbiota interactions on human health, disease onset and progression, and on host response to treatments has increasingly emerged in the latest decades. Indeed, dysbiosis has been associated to several human diseases such as obesity, diabetes, cancer and also neurodegenerative disease, such as Parkinson, Huntington and Alzheimer's disease (AD), although whether causative, consequence or merely an epiphenomenon is still under investigation. In the present study, we performed a metabologenomic analysis of stool samples from a mouse model of AD, the 3xTgAD. We found a significant change in the microbiota of AD mice compared to WT, with a longitudinal divergence of the F/B ratio, a parameter suggesting a gut dysbiosis. Moreover, AD mice showed a significant decrease of some amino acids, while data integration revealed a dysregulated production of desaminotyrosine (DAT) and dihydro-3-coumaric acid. Collectively, our data show a dysregulated gut microbiota associated to the onset and progression of AD, also indicating that a dysbiosis can occur prior to significant clinical signs, evidenced by early SCFA alterations, compatible with gut inflammation.
近年来，宿主-微生物群相互作用对人类健康、疾病的发生和发展以及宿主对治疗的反应的关键作用日益凸显。事实上，肠道菌群失调与多种人类疾病有关，如肥胖症、糖尿病、癌症，也与神经退行性疾病有关，如帕金森病、亨廷顿病和阿尔茨海默病（AD），尽管其是否是致病因素、后果还是仅仅是一种伴随现象仍在研究之中。在本研究中，我们对 AD 小鼠模型（3xTgAD）的粪便样本进行了代谢组学和基因组学分析。与 WT 相比，AD 小鼠的肠道微生物群发生了显著变化，F/B 比值纵向发散，这是肠道菌群失调的一个参数。此外，AD 小鼠的一些氨基酸含量显著下降，而数据整合显示脱氨酶酪氨酸（DAT）和二氢-3-香豆酸的产生失调。总的来说，我们的数据显示 AD 发病和进展与肠道菌群失调有关，同时也表明，在出现明显的临床症状之前就可能发生菌群失调，这可以通过早期 SCFA 改变来证明，这与肠道炎症是一致的。
