Journal Article

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

Hui, Yan, Zhao, Tong, Wang, Luanfeng, Shi, Renjie, Wang, Danna, Jin, Xin, Pan, Junru, Liu, Xuebo, Zhang, Hongbo, Yuan, Tian, Wang, Jiamin, Shi, Lin, Yin, Fei, Tan, Xintong, Lan, Lei, Liu, Zhigang, Ren, Bo, Dai, Xiaoshuang, Chu, Chuanqi, Wang, Jia, Zhang, Wentong, Cadenas, Enrique, Zhao, Shancen, Wang, Qianxu, Liu, Xiaoning

2020

Overview

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. Intermittent fasting (IF) has been shown beneficial in reducing metabolic diseases. Here, using a multi-omics approach in a T2D mouse model, the authors report that IF alters the composition of the gut microbiota and improves metabolic phenotypes that correlate with cognitive behavior.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/1 / 13/51 / 14/28 / 14/63 / 38/47 / 38/88 / 49/91 / 631/114 / 631/326 / 631/378 / 631/45 / 64/110 / 64/60 / 692/699 / 82/29 / 82/51 / 82/80 / 96/1 / Animals / Antibiotics / Brain / Brain - metabolism / Cognition / Cognition & reasoning / Cognitive ability / Cognitive Dysfunction - metabolism / Computational Biology / Diabetes / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Experimental / Diabetes Mellitus, Type 2 - complications / Diabetes Mellitus, Type 2 - metabolism / Energy metabolism / Energy Metabolism - genetics / Fasting / Fatty acids / Fatty Acids, Volatile - metabolism / Gastrointestinal Microbiome - genetics / Gastrointestinal Microbiome - physiology / Gene expression / Gene Expression Regulation / Gut microbiota / Hippocampus - metabolism / Humanities and Social Sciences / Impairment / Indoles - metabolism / Insulin Resistance / Intestinal microflora / Male / Metabolic disorders / Metabolism / Metabolites / Metabolome / Mice / Microbiota / Microorganisms / Mitochondria / multidisciplinary / Neuroprotection / Phenotypes / Propionates - metabolism / RNA, Ribosomal, 16S / Science / Science (multidisciplinary) / Serotonin / Serotonin - metabolism / Signs and symptoms / Synapses - ultrastructure / Taurochenodeoxycholic Acid - metabolism / Tauroursodeoxycholic acid