Prebiotics Regulation of Intestinal Microbiota Attenuates Cognitive Dysfunction Induced by Surgery Stimulation in APP/PS1 Mice.

Cheng Ni,Dengyang Han,Jindan He,Min Qian,Ning Yang,Taotao Liu,Wen Zhang,Xiangyang Guo,Yue Li,Zhengqian Li,Zhongshen Kuang

doi:10.14336/ad.2020.0106

Abstract

Emerging evidence indicates that the intestinal microbiota could interact with the central nervous system and modulate multiple pathophysiological changes, including the integrity of intestinal barrier and blood-brain barrier, as well as neuroinflammatory response. In the present study, we investigated the potential role of intestinal microbiota in the pathophysiological process of postoperative cognitive dysfunction. Six-month-old APP/PS1 mice were subjected to partial hepatectomy to establish surgery model and exhibited cognitive dysfunction. The expressions of inflammatory mediators increased and tight junction proteins (ZO-1 and Occludin) levels decreased in the intestine and hippocampus. The 16S ribosomal RNA gene sequencing showed altered β diversity and intestinal microbiota richness after surgery, including genus Rodentibacter, Bacteroides, Ruminococcaceae_UCG_014 and Faecalibaculum, as well as family Eggerthellaceae and Muribaculaceae. Furthermore, prebiotics (Xylooligosaccharides, XOS) intervention effectively attenuated surgery-induced cognitive dysfunction and intestinal microbiota alteration, reduced inflammatory responses, and improved the integrity of tight junction barrier in the intestine and hippocampus. In summary, the present study indicates that intestinal microbiota alteration, the related intestinal barrier and blood-brain barrier damage, and inflammatory responses participate the pathophysiological process of postoperative cognitive dysfunction. Prebiotics intervention could be a potential preventative approach.

Highlights

Emerging evidence indicates that the intestinal microbiota could interact with the central nervous system and modulate multiple pathophysiological changes, including the integrity of intestinal barrier and blood-brain barrier, as well as neuroinflammatory response
We speculate that dysregulation of intestinal microbiota could affect systemic inflammatory response, disrupt the barrier integrity in intestine and central nervous system (CNS), which lead to the development of Postoperative cognitive dysfunction (POCD)
The principal co-ordinates analysis (PCoA) in β diversity analysis showed that the intestinal microbiota distribution after surgery was distinguished from normal condition, which indicates that surgery stimulation disrupted the intestinal microbiota balance in APP/PS1 mice

Summary

Introduction

Emerging evidence indicates that the intestinal microbiota could interact with the central nervous system and modulate multiple pathophysiological changes, including the integrity of intestinal barrier and blood-brain barrier, as well as neuroinflammatory response. Prebiotics (Xylooligosaccharides, XOS) intervention effectively attenuated surgery-induced cognitive dysfunction and intestinal microbiota alteration, reduced inflammatory responses, and improved the integrity of tight junction barrier in the intestine and hippocampus. The present study indicates that intestinal microbiota alteration, the related intestinal barrier and blood-brain barrier damage, and inflammatory responses participate the pathophysiological process of postoperative cognitive dysfunction. Ours and related studies found that peripheral inflammatory mediators induced by anesthesia and surgery could infiltrate the CNS through disrupted BBB and lead to cognitive dysfunction [8, 9]. Xylooligosaccharides (XOS), a prebiotics fiber composed of 2-7 xylose molecules bound by β-1,4 glycoside bonds, has been proved to be beneficial in both clinical and animal studies, including downregulating the proportion of pathogenic bacteria of intestinal tract, decreasing peripheral and central inflammatory mediators [3, 12, 13].

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Results

Conclusion