Research Paper Volume 13, Issue 7 pp 10058—10074
Gut microbiota from mice with cerebral ischemia-reperfusion injury affects the brain in healthy mice
- 1 Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China
- 2 Department of Neurology, Liaocheng People’s Hospital, Liaocheng 252000, Shandong, China
- 3 Department of Neurosurgery, Liaocheng People’s Hospital, Liaocheng 252000, Shandong, China
- 4 Department of Neurology, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250000, Shandong, China
Received: May 30, 2020 Accepted: January 13, 2021 Published: March 26, 2021
https://doi.org/10.18632/aging.202763How to Cite
Copyright: © 2021 Wang 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
Gut microorganisms can profoundly influence brain function in the host and their behavior. Since altered brain functional connectivity (FC) has been implicated in various cerebrovascular disorders, including cerebral ischemia-reperfusion (I/R) injury, we hypothesized that gut microbiota in mice with cerebral I/R injury would affect brain FC when transplanted into germ-free mice. Metagenomic analysis of germ-free male C57BL/6J mice colonized with microbiota from mice with and without cerebral I/R injury showed a clear distinction in microbiota composition between mice colonized with control and I/R microbiota. The I/R microbiota-colonized mice showed decreased FC in the cingulate cortex, hippocampus, and thalamus, and exhibited increased anxiety as well as diminished spatial learning and memory and short-term object recognition memory. I/R microbiota-colonized mice also had significantly reduced dendritic spine density and synaptic protein levels and exhibited increased hippocampal inflammation. These results indicate that gut microbiota components from mice with cerebral I/R injury can alter animal behavior, brain functional connectivity, hippocampal neuronal plasticity, and neuroinflammation. Moreover, they increase our understanding of the mechanisms through which the gut microbiome contributes to the pathobiology of cerebrovascular diseases.