Research Paper Volume 12, Issue 9 pp 7801—7817

Age-related shifts in gut microbiota contribute to cognitive decline in aged rats

Yanli Li 1, 2, , Li Ning 1, , Yiru Yin 1, , Rui Wang 2, , Zhiyong Zhang 1, , Lijun Hao 1, , Bin Wang 3, , Xin Zhao 1, , Xiaorong Yang 1, , Litian Yin 1, , Shufen Wu 1, , Dawei Guo 1, , Ce Zhang 1, ,

  • 1 Key Laboratory of Cellular Physiology, Ministry of Education, Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi, P.R. China
  • 2 Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, P.R. China
  • 3 College of Information and Computer, Taiyuan University of Technology, Taiyuan 030024, Shanxi, P.R. China

received: October 18, 2019 ; accepted: March 24, 2020 ; published: May 1, 2020 ;

https://doi.org/10.18632/aging.103093
How to Cite

Copyright © 2020 Li 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

Cognitive function declines during the aging process, meanwhile, gut microbiota of the elderly changed significantly. Although previous studies have reported the effect of gut microbiota on learning and memory, all the reports were based on various artificial interventions to change the gut microbiota without involvement of aging biological characteristics. Here, we investigated the effect of aged gut microbiota on cognitive function by using fecal microbiota transplantation (FMT) from aged to young rats. Results showed that FMT impaired cognitive behavior in young recipient rats; decreased the regional homogeneity in medial prefrontal cortex and hippocampus; changed synaptic structures and decreased dendritic spines; reduced expression of brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartate receptor NR1 subunit, and synaptophysin; increased expression of advanced glycation end products (AGEs) and receptor for AGEs (RAGE). All these behavioral, brain structural and functional alterations induced by FMT reflected cognitive decline. In addition, FMT increased levels of pro-inflammatory cytokines and oxidative stress in young rats, indicating that inflammation and oxidative stress may underlie gut-related cognitive decline in aging. This study provides direct evidence for the contribution of gut microbiota to the cognitive decline during normal aging and suggests that restoring microbiota homeostasis in the elderly may improve cognitive function.

Abbreviations

DMTP: delayed matching to position; ReHo: regional homogeneity; OTU: Operational Taxonomic Unit; BOLD: blood oxygenation level dependent; FMT: fecal microbiota transplantation; rs-fMRI: resting-state functional magnetic resonance; mPFC: medial prefrontal cortex; PSD: post-synaptic density; SOD: superoxide dismutase; GSH-PX: glutathione peroxidase; MDA: malondialdehyde; NMDA: N-methyl-D-aspartate; BDNF: brain derived neurotrophic factor; NMDS: Nonmetric Multidimensional Scaling; AGE: advanced glycation end products; RAGE: receptor for advanced glycation end products.