Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment
Journal article, 2020
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.
Author
Zhigang Liu
Northwest A&F university
Xiaoshuang Dai
BGI Institute of Applied Agriculture
Hongbo Zhang
Northwest A&F university
Renjie Shi
Northwest A&F university
Yan Hui
BGI Institute of Applied Agriculture
University of Copenhagen
Xin Jin
BGI Institute of Applied Agriculture
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 Institute of Applied Agriculture
Fei Yin
University of Arizona
Enrique Cadenas
University of Southern California
Lin Shi
Chalmers, Biology and Biological Engineering, Food and Nutrition Science
Shancen Zhao
BGI Institute of Applied Agriculture
Xuebo Liu
Northwest A&F university
Nature Communications
2041-1723 (ISSN) 20411723 (eISSN)
Vol. 11 1 855- 855Subject Categories
Endocrinology and Diabetes
Other Clinical Medicine
Neurosciences
DOI
10.1038/s41467-020-14676-4
PubMed
32071312