Ling Zongxin, Zhu Manlian, Yan Xiumei, Cheng Yiwen, Shao Li, Liu Xia, Jiang Ruilai, Wu Shaochang
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
Department of Geriatrics, Lishui Second People's Hospital, Lishui, China.
Front Cell Dev Biol. 2021 Feb 4;8:634069. doi: 10.3389/fcell.2020.634069. eCollection 2020.
Increasing evidence suggests that gut dysbiosis plays vital roles in a variety of gut-brain disorders, such as Alzheimer's disease (AD). However, alterations of the gut microbiota as well as their correlations with cognitive scores and host immunity have remained unclear in well-controlled trials on Chinese AD patients. In this study, samples from 100 AD patients, and 71 age- and gender-matched, cognitively normal controls were obtained to explore the structural and functional alterations of the fecal microbiota targeting the V3-V4 region of the 16S rRNA gene by MiSeq sequencing, and to analyze their associations with clinical characteristics. Our data demonstrated a remarkably reduction in the bacterial diversity and alterations in the taxonomic composition of the fecal microbiota of the AD patients. Interestingly, the abundant butyrate-producing genera such as decreased significantly, where this was positively correlated with such clinical indicators as the MMSE, WAIS, and Barthel scores in the AD patients. On the contrary, abundant lactate-producing genera, such as , increased prominently, and were inversely correlated with these indicators. This shift in the gut dysbiosis of the microbiota, from being butyrate producers to lactate producers, contributed to immune disturbances in the host that could be used as non-invasive biomarkers to distinguish the controls from the AD patients. Moreover, several predicted functional modules, including the biosynthesis and the metabolism of fatty acids, that were altered in the microbiota of the AD patients could be utilized by the bacteria to produce immunomodulatory metabolites. Our study established the structural and functional dysbiosis of fecal microbiota in AD patients, and the results suggest the potential for use of gut bacteria for the early, non-invasive diagnosis of AD, personalized treatment, and the development of tailor-made probiotics designed for Chinese AD patients.
越来越多的证据表明，肠道微生物群失调在多种肠道-脑疾病中起着至关重要的作用，如阿尔茨海默病（AD）。然而，在中国AD患者的严格对照试验中，肠道微生物群的变化及其与认知评分和宿主免疫的相关性仍不清楚。在本研究中，获取了100例AD患者以及71例年龄和性别匹配、认知正常的对照者的样本，通过MiSeq测序探索靶向16S rRNA基因V3-V4区域的粪便微生物群的结构和功能变化，并分析它们与临床特征的关联。我们的数据表明，AD患者粪便微生物群的细菌多样性显著降低，分类组成发生改变。有趣的是，AD患者中大量产丁酸的菌属（如 ）显著减少，且与MMSE、WAIS和Barthel评分等临床指标呈正相关。相反，大量产乳酸的菌属（如 ）显著增加，且与这些指标呈负相关。微生物群的这种肠道失调转变，从产丁酸菌变为产乳酸菌，导致宿主免疫紊乱，可作为区分对照者和AD患者的非侵入性生物标志物。此外，AD患者微生物群中几个预测的功能模块，包括脂肪酸的生物合成和代谢，可被细菌利用来产生免疫调节代谢物。我们的研究确定了AD患者粪便微生物群的结构和功能失调，结果表明肠道细菌在AD的早期非侵入性诊断、个性化治疗以及为中国AD患者设计量身定制的益生菌方面具有潜在应用价值。
