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 Faecalibacterium 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 Bifidobacterium, 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.

本周为大家带来的文献为发表于Front Cell Dev Biol. (IF: 5.5)的” Structural and Functional Dysbiosis of Fecal Microbiota in Chinese Patients With Alzheimer's Disease”。本文使用了LabEx提供的Luminex检测服务。

阿尔茨海默病（AD）是一种与年龄有关的神经退行性疾病，以缓慢进行性记忆力衰退和认知功能障碍为特征，目前尚无预防或改变病情的治疗方法。越来越多的证据表明，肠道菌群失调在阿尔茨海默病等多种肠脑疾病中起着至关重要的作用。然而，在对中国AD患者进行的良好对照试验中，肠道微生物群的改变及其与认知评分和宿主免疫的相关性仍不清楚。

LabEx提供的Luminex检测服务：

这些参与者的血清样本是在清晨利用空腹血液采集的。使用27种磁珠免疫测定试剂盒（Bio-Rad）对以下细胞因子进行了量化：白细胞介素-1β（IL-1β）、IL-1受体拮抗剂（IL-1ra）、IL-2、IL-4、IL-5、IL-6、IL-7、IL-8、IL-9、IL-10、IL-12（p70）、IL-13、IL-15、IL-17、Eotaxin、成纤维细胞生长因子基础（FGF-basic）、粒细胞集落刺激因子（G-CSF）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、γ干扰素（IFN-γ）、单核细胞趋化蛋白-1（MCP-1）、巨噬细胞炎症蛋白-1α（MIP-1α）、血小板衍生生长因子（PDGF-bb）、MIP-1β、正常T细胞表达和分泌激活调节因子（RANTES）、肿瘤坏死因子-α（TNF-α）和血管内皮生长因子（VEGF）。

通过使用Bio-PlexPro™人类细胞因子I组27复合物分析（LXLBH27-1），我们观察到IFN-γ等抗炎细胞因子明显减少，TNF-α等促炎细胞因子明显增加，IL-8、MCP-1和MIP-1a等几种趋化因子明显减少。在中国的AD患者中，IP-10也有所下降。

粪便微生物群、促炎和抗炎细胞因子及趋化因子与临床指标之间的相关性。

重要发现：

本研究采集了100例AD患者和71例年龄与性别匹配、认知正常的对照组样本，通过MiSeq测序技术探讨了粪便微生物群结构和功能的改变，这些改变以16SrRNA基因的V3-V4区域为目标，并分析了它们与临床特征的关系。我们的数据表明，AD患者粪便微生物群的细菌多样性明显减少，分类组成也发生了改变。有趣的是，产生大量丁酸盐的菌属，如粪杆菌（Faecalibacterium）明显减少，这与AD患者的MMSE、WAIS和Barthel评分等临床指标呈正相关。相反，双歧杆菌等大量产生乳酸的菌属则明显增加，并与这些指标成反比。

微生物群的肠道菌群失调从丁酸生产者转变为乳酸生产者，导致了宿主的免疫紊乱，这种紊乱可作为非侵入性生物标志物来区分对照组和注意力缺失症患者。此外，一些预测的功能模块（包括脂肪酸的生物合成和代谢）在AD患者的微生物群中发生了改变，这些功能模块可被细菌利用来产生免疫调节代谢产物。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，结果表明肠道细菌有可能被用于AD的早期非侵入性诊断、个性化治疗，以及开发专为中国AD患者设计的定制益生菌。