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; Xuebo Liu

doi:10.1038/s41467-020-14676-4

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 LanFei Yin, Enrique Cadenas, Lin Shi, Shancen Zhao, Xuebo Liu

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362 Scopus citations

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.

Original language	English (US)
Article number	855
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-14676-4
State	Published - Dec 1 2020
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Liu, Z., Dai, X., Zhang, H., Shi, R., Hui, Y., Jin, X., Zhang, W., Wang, L., Wang, Q., Wang, D., Wang, J., Tan, X., Ren, B., Liu, X., Zhao, T., Wang, J., Pan, J., Yuan, T., Chu, C., ... Liu, X. (2020). Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment. Nature communications, 11(1), Article 855. https://doi.org/10.1038/s41467-020-14676-4

Liu, Z, Dai, X, Zhang, H, Shi, R, Hui, Y, Jin, X, Zhang, W, Wang, L, Wang, Q, Wang, D, Wang, J, Tan, X, Ren, B, Liu, X, Zhao, T, Wang, J, Pan, J, Yuan, T, Chu, C, Lan, L, Yin, F, Cadenas, E, Shi, L, Zhao, S & Liu, X 2020, 'Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment', Nature communications, vol. 11, no. 1, 855. https://doi.org/10.1038/s41467-020-14676-4

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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.",

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

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AU - Liu, Zhigang

AU - Dai, Xiaoshuang

AU - Zhang, Hongbo

AU - Shi, Renjie

AU - Hui, Yan

AU - Jin, Xin

AU - Zhang, Wentong

AU - Wang, Luanfeng

AU - Wang, Qianxu

AU - Wang, Danna

AU - Wang, Jia

AU - Tan, Xintong

AU - Ren, Bo

AU - Liu, Xiaoning

AU - Zhao, Tong

AU - Wang, Jiamin

AU - Pan, Junru

AU - Yuan, Tian

AU - Chu, Chuanqi

AU - Lan, Lei

AU - Yin, Fei

AU - Cadenas, Enrique

AU - Shi, Lin

AU - Zhao, Shancen

AU - Liu, Xuebo

PY - 2020/12/1

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N2 - 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.

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

Abstract

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