Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment

Zhigang Liu (), Xiaoshuang Dai, Hongbo Zhang, Renjie Shi, Yan Hui, Xin Jin, Wentong Zhang, Luanfeng Wang, Qianxu Wang, Danna Wang, Jia Wang, Xintong Tan, Bo Ren, Xiaoning Liu, Tong Zhao, Jiamin Wang, Junru Pan, Tian Yuan, Chuanqi Chu, Lei Lan, Fei Yin, Enrique Cadenas, Lin Shi (), Shancen Zhao () and Xuebo Liu ()
Additional contact information
Zhigang Liu: Northwest A&F University
Xiaoshuang Dai: BGI-Shenzhen
Hongbo Zhang: Northwest A&F University
Renjie Shi: Northwest A&F University
Yan Hui: BGI-Shenzhen
Xin Jin: BGI-Shenzhen
Wentong Zhang: Northwest A&F University
Luanfeng Wang: Northwest A&F University
Qianxu Wang: Northwest A&F University
Danna Wang: Northwest A&F University
Jia Wang: Northwest A&F University
Xintong Tan: Northwest A&F University
Bo Ren: Northwest A&F University
Xiaoning Liu: Northwest A&F University
Tong Zhao: Northwest A&F University
Jiamin Wang: Northwest A&F University
Junru Pan: Northwest A&F University
Tian Yuan: Northwest A&F University
Chuanqi Chu: Northwest A&F University
Lei Lan: BGI-Shenzhen
Fei Yin: University of Arizona
Enrique Cadenas: University of Southern California
Lin Shi: Chalmers University of Technology
Shancen Zhao: BGI-Shenzhen
Xuebo Liu: Northwest A&F University

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Cognitive decline is one of the complications of type 2 diabetes (T2D). Intermittent fasting (IF) is a promising dietary intervention for alleviating T2D symptoms, but its protective effect on diabetes-driven cognitive dysfunction remains elusive. Here, we find that a 28-day IF regimen for diabetic mice improves behavioral impairment via a microbiota-metabolites-brain axis: IF enhances mitochondrial biogenesis and energy metabolism gene expression in hippocampus, re-structures the gut microbiota, and improves microbial metabolites that are related to cognitive function. Moreover, strong connections are observed between IF affected genes, microbiota and metabolites, as assessed by integrative modelling. Removing gut microbiota with antibiotics partly abolishes the neuroprotective effects of IF. Administration of 3-indolepropionic acid, serotonin, short chain fatty acids or tauroursodeoxycholic acid shows a similar effect to IF in terms of improving cognitive function. Together, our study purports the microbiota-metabolites-brain axis as a mechanism that can enable therapeutic strategies against metabolism-implicated cognitive pathophysiologies.

Date: 2020
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DOI: 10.1038/s41467-020-14676-4

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