Research Paper Volume 11, Issue 10 pp 3262—3279

Abnormal gut microbiota composition contributes to cognitive dysfunction in streptozotocin-induced diabetic mice

Fan Yu 1, , Wei Han 2, , Gaofeng Zhan 3, , Shan Li 3, , Shoukui Xiang 1, , Bin Zhu 4, , Xiaohong Jiang 1, , Ling Yang 5, , Ailin Luo 3, , Fei Hua 1, , Chun Yang 3, ,

  • 1 Department of Endocrinology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
  • 2 Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
  • 3 Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
  • 4 Department of Critical Care Medicine, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
  • 5 Department of Cardiology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China

received: April 16, 2019 ; accepted: May 12, 2019 ; published: May 23, 2019 ;

https://doi.org/10.18632/aging.101978
How to Cite

Copyright: Yu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Both diabetes and Alzheimer’s disease are age-related disorders, and numerous studies have demonstrated that patients with diabetes are at an increased risk of cognitive dysfunction (CD) and Alzheimer’s disease, suggesting shared or interacting pathomechanisms. The present study investigated the role of abnormal gut microbiota in diabetes-induced CD and the potential underlying mechanisms. An intraperitoneal injection of streptozotocin administered for 5 consecutive days was used for establishing a diabetic animal model. Hierarchical cluster analysis of Morris water maze (MWM) performance indices (escape latency and target quadrant crossing) was adopted to classify the diabetic model mice into CD and Non-CD phenotypes. Both β-diversity and relative abundance of several gut bacteria significantly differed between the CD and Non-CD groups. Further, fecal bacteria transplantation from Non-CD mice, but not from CD mice, into the gut of pseudo-germ-free mice significantly improved host MWM performance, an effect associated with alterations in β-diversity and relative abundance of host gut bacteria. Collectively, these findings suggest that abnormal gut microbiota composition contributes to the onset of diabetes-induced CD and that improving gut microbiota composition is a potential therapeutic strategy for diabetes and related comorbidities.

Abbreviations

Aβ: amyloid β; ANOVA: analysis of variance; AUC: area under the curve; CD: cognitive dysfunction; CONT: control; MWM: Morris water maze; PCR: polymerase chain reaction; PCoA: principal coordinate analysis; PLS-DA: partial least squares discrimination analysis; ROC: receiver operating characteristic; SEM: standard error of the mean; STZ: streptozotocin.