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

被引：422

作者：

Liu, Zhigang ^{[1
]}

Dai, Xiaoshuang ^{[2
]}

Zhang, Hongbo ^{[1
]}

Shi, Renjie ^{[1
]}

Hui, Yan ^{[2
,3
]}

Jin, Xin ^{[2
]}

Zhang, Wentong ^{[1
]}

Wang, Luanfeng ^{[1
]}

Wang, Qianxu ^{[1
]}

Wang, Danna ^{[1
]}

Wang, Jia ^{[1
]}

Tan, Xintong ^{[1
]}

Ren, Bo ^{[1
]}

Liu, Xiaoning ^{[1
]}

Zhao, Tong ^{[1
]}

Wang, Jiamin ^{[1
]}

Pan, Junru ^{[1
]}

Yuan, Tian ^{[1
]}

Chu, Chuanqi ^{[1
]}

Lan, Lei ^{[2
]}

Yin, Fei ^{[4
,5
]}

Cadenas, Enrique ^{[6
]}

Shi, Lin ^{[7
]}

Zhao, Shancen ^{[2
]}

Liu, Xuebo ^{[1
]}

机构：

[1] Northwest A&F Univ, Coll Food Sci & Engn, Yangling 712100, Shaanxi, Peoples R China

[2] BGI Shenzhen, BGI Inst Appl Agr, Shenzhen 518120, Peoples R China

[3] Univ Copenhagen, Dept Food Sci, DK-1958 Copenhagen, Denmark

[4] Univ Arizona, Ctr Innovat Brain Sci, Tucson, AZ 85721 USA

[5] Univ Arizona, Dept Pharmacol, Tucson, AZ 85721 USA

[6] Univ Southern Calif, Sch Pharm, Pharmacol & Pharmaceut Sci, Los Angeles, CA 90089 USA

[7] Chalmers Univ Technol, Dept Biol & Biol Engn, Div Food & Nutr Sci, SE-41296 Gothenburg, Sweden

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

DIETARY RESTRICTION; WATER-MAZE; BILE-ACID; BRAIN; METRONIDAZOLE; RECEPTOR; OBESITY; INFLAMMATION; PROTECTION; AUTOPHAGY;

D O I：

10.1038/s41467-020-14676-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14

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