Gut Microbiota Mediates Intermittent-fasting Alleviation of Diabetes-induced Cognitive Impairment

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Feb 20

PMID 32071312

Citations 179

Authors

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

Xuebo Liu

Affiliations

Soon will be listed here.

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.

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