Department of Anesthesiology, Xuanwu Hospital, Beijing, China.
Department of Orthopedics, Xuanwu Hospital, Beijing, China.
Front Cell Infect Microbiol. 2021 Mar 29;11:592842. doi: 10.3389/fcimb.2021.592842. eCollection 2021.
Emerging evidence links perturbations in the microbiome to neurodegeneration in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) and to surgical stress. In this study, we attempted to identify preoperative differences intestinal microbiota (IM) and barrier function between pAD [prodromal AD: Subjective cognitive decline (SCD) and aMCI] patients and normal neurocognition (NC) patients. Additionally, the potential associations between IM and barrier function, inflammation, and the clinical characteristics of pAD were evaluated.
Eighty elderly patients scheduled to undergo orthopedic surgery were consecutively enrolled and grouped as NC, SCD, and aMCI following neuropsychological assessment. IM was determined by 16S rRNA MiSeq sequencing, and PICRUSt was used to predict functional shifts in IM. Furthermore, we investigated the association between IM and plasma claudin-1, occludin, LPS, systemic inflammatory cytokines, neuropsychological assessment, and clinical characteristics.
There was a lower Chao1 index in the SCD group (P = 0.004) and differences in beta diversity among the three groups (PCA: P = 0.026, PCoA: P= 0.004). The relative abundance of was higher in the SCD group (P = 0.016, P = 0.008), and were more enriched in the aMCI group than in the SCD group (P= 0.026). At the family level, the total abundance of Gram-negative bacteria was higher in the SCD group than in the aMCI group (P = 0.047), and the family was detected at lower levels in the SCD and aMCI groups than in the NC group (P= 0.039). At the genus level, the eleven short-chain fatty acid (SCFA)-producing bacteria exhibited differences among the three groups. PICRUSt analysis showed that the pathways involved in SCFA catabolism, biosynthesis, and adherent junctions were reduced in SCD patients, and lipid synthesis proteins were reduced in pAD patients. Meanwhile, elevated plasma LPS and CRP were observed in SCD patients, and higher plasma occludin in aMCI patients. The IM was correlated with plasma claudin-1, LPS, inflammatory factors, neuropsychological assessment, and clinical characteristics.
The intestines of SCD and aMCI patients preoperatively exhibited IM dysbiosis and barrier dysfunction, and elevated plasma LPS and CRP were observed in SCD patients.
新出现的证据表明，微生物组的紊乱与遗忘型轻度认知障碍（aMCI）和阿尔茨海默病（AD）的神经退行性变以及手术应激有关。在这项研究中，我们试图确定术前肠道微生物组（IM）和屏障功能在前驱 AD [主观认知下降（SCD）和 aMCI]患者与正常神经认知（NC）患者之间的差异。此外，还评估了 IM 与屏障功能、炎症和前驱 AD 临床特征之间的潜在关联。
连续纳入 80 名拟行骨科手术的老年患者，根据神经心理学评估结果分为 NC、SCD 和 aMCI 组。通过 16S rRNA MiSeq 测序确定 IM，并用 PICRUSt 预测 IM 功能变化。此外，我们还研究了 IM 与血浆 Claudin-1、occludin、LPS、全身炎症细胞因子、神经心理学评估和临床特征之间的关系。
SCD 组的 Chao1 指数较低（P=0.004），三组间的 beta 多样性存在差异（PCA：P=0.026，PCoA：P=0.004）。SCD 组的相对丰度较高（P=0.016，P=0.008），aMCI 组的相对丰度高于 SCD 组（P=0.026）。在科水平上，SCD 组的革兰氏阴性菌总丰度高于 aMCI 组（P=0.047），SCD 和 aMCI 组的丰度低于 NC 组（P=0.039）。在属水平上，三组间的 11 种短链脂肪酸（SCFA）产生菌存在差异。PICRUSt 分析显示，SCD 患者涉及 SCFA 分解代谢、生物合成和粘着连接的途径减少，pAD 患者的脂质合成蛋白减少。同时，SCD 患者的血浆 LPS 和 CRP 升高，aMCI 患者的血浆 occludin 升高。IM 与血浆 Claudin-1、LPS、炎症因子、神经心理学评估和临床特征相关。
SCD 和 aMCI 患者术前肠道存在 IM 失调和屏障功能障碍，SCD 患者血浆 LPS 和 CRP 升高。
