AUTHOR=Duan Mei , Liu Fangyan , Fu Huiqun , Lu Shibao , Wang Tianlong 

TITLE=Preoperative Microbiomes and Intestinal Barrier Function Can Differentiate Prodromal Alzheimer’s Disease From Normal Neurocognition in Elderly Patients Scheduled to Undergo Orthopedic Surgery

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.592842

DOI=10.3389/fcimb.2021.592842

ISSN=2235-2988

ABSTRACT=ABSTRACT
Objective:
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 in IM and intestinal barrier function between pAD (prodromal AD: SCD and aMCI) patients and normal neurocognition (NC) patients. Additionally, the potential associations between IM and intestinal barrier function, inflammation and the clinical characteristics of pAD were evaluated.
Design:
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.
Results: 
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 = 0.007). The relative abundance of Bacteroidetes was higher in the SCD group (P = 0.012), and Firmicutes were more enriched in the aMCI group than in the SCD group (P = 0.025). 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 Christensenellaceae family was detected at lower levels in the SCD and aMCI groups than in the NC group (P = 0.021, P = 0.032). 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 LPS and CRP were observed in SCD patients, and higher plasma occludin in aMCI patients. The IM was correlated with claudin-1, LPS, inflammatory factors, neuropsychological assessment and clinical characteristics.
Conclusion:
The intestines of SCD and aMCI patients preoperatively exhibited IM dysbiosis and barrier dysfunction, and elevated levels of plasma LPS and low-grade systemic inflammation were observed in SCD patients.