Gut Microbiota Alteration Is Associated With Cognitive Deficits in Genetically Diabetic (Db/db) Mice During Aging

Recent studies have revealed that the microbiota may be implicated in diabetes-related cognitive dysfunction. However, the relationship between gut microbiota and cognitive dysfunction during the progression of type 2 diabetes remains elusive. We used 16S rRNA sequencing combined with conventional b...

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Main Authors: Jiawei Zhang, Yaxuan Zhang, Yuan Yuan, Lan Liu, Yuwu Zhao, Xiuzhe Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-01-01
Series:Frontiers in Aging Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnagi.2021.815562/full
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author Jiawei Zhang
Yaxuan Zhang
Yuan Yuan
Lan Liu
Yuwu Zhao
Xiuzhe Wang
author_facet Jiawei Zhang
Yaxuan Zhang
Yuan Yuan
Lan Liu
Yuwu Zhao
Xiuzhe Wang
author_sort Jiawei Zhang
collection DOAJ
description Recent studies have revealed that the microbiota may be implicated in diabetes-related cognitive dysfunction. However, the relationship between gut microbiota and cognitive dysfunction during the progression of type 2 diabetes remains elusive. We used 16S rRNA sequencing combined with conventional behavioral tests to explore the longitudinal changes of gut microbiota and cognition in diabetic db/db mice (leptin receptor knockout mice) and their wild-type littermates at different ages. Prussian blue staining was performed to detect the microhemorrhage in the brain, and immunofluorescent study was applied to analyze microglia activation. Moreover, a Meso Scale Discovery kit was used to determine the cytokine levels in the brain. Db/db mice exhibited age dependent pathological characteristics, including cognitive deficits, neuron damage, spontaneous hemorrhages and neuroinflammation. Furthermore, we observed that the diversity and composition of gut microbiota significantly differed between the wild-type and db/db mice during aging. We found that compared to age-matched wild-type mice, genus Helicobacter was significant higher in db/db mice at 18 and 26 weeks. Correlation analysis revealed that Helicobacter is positively associated with Iba-1 positive cells and TNF-α expression. Collectively, our longitudinal study suggests that diabetic cognitive impairment during aging is associated with abnormal gut microbiota composition, which may play a role in the regulation of neuroinflammation.
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spelling doaj.art-62350de6614a4fd2bb0685c84c54b51c2022-12-21T19:43:53ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652022-01-011310.3389/fnagi.2021.815562815562Gut Microbiota Alteration Is Associated With Cognitive Deficits in Genetically Diabetic (Db/db) Mice During AgingJiawei ZhangYaxuan ZhangYuan YuanLan LiuYuwu ZhaoXiuzhe WangRecent studies have revealed that the microbiota may be implicated in diabetes-related cognitive dysfunction. However, the relationship between gut microbiota and cognitive dysfunction during the progression of type 2 diabetes remains elusive. We used 16S rRNA sequencing combined with conventional behavioral tests to explore the longitudinal changes of gut microbiota and cognition in diabetic db/db mice (leptin receptor knockout mice) and their wild-type littermates at different ages. Prussian blue staining was performed to detect the microhemorrhage in the brain, and immunofluorescent study was applied to analyze microglia activation. Moreover, a Meso Scale Discovery kit was used to determine the cytokine levels in the brain. Db/db mice exhibited age dependent pathological characteristics, including cognitive deficits, neuron damage, spontaneous hemorrhages and neuroinflammation. Furthermore, we observed that the diversity and composition of gut microbiota significantly differed between the wild-type and db/db mice during aging. We found that compared to age-matched wild-type mice, genus Helicobacter was significant higher in db/db mice at 18 and 26 weeks. Correlation analysis revealed that Helicobacter is positively associated with Iba-1 positive cells and TNF-α expression. Collectively, our longitudinal study suggests that diabetic cognitive impairment during aging is associated with abnormal gut microbiota composition, which may play a role in the regulation of neuroinflammation.https://www.frontiersin.org/articles/10.3389/fnagi.2021.815562/fulltype 2 diabetescognitive dysfunctiongut microbiotaneuroinflammationaging
spellingShingle Jiawei Zhang
Yaxuan Zhang
Yuan Yuan
Lan Liu
Yuwu Zhao
Xiuzhe Wang
Gut Microbiota Alteration Is Associated With Cognitive Deficits in Genetically Diabetic (Db/db) Mice During Aging
Frontiers in Aging Neuroscience
type 2 diabetes
cognitive dysfunction
gut microbiota
neuroinflammation
aging
title Gut Microbiota Alteration Is Associated With Cognitive Deficits in Genetically Diabetic (Db/db) Mice During Aging
title_full Gut Microbiota Alteration Is Associated With Cognitive Deficits in Genetically Diabetic (Db/db) Mice During Aging
title_fullStr Gut Microbiota Alteration Is Associated With Cognitive Deficits in Genetically Diabetic (Db/db) Mice During Aging
title_full_unstemmed Gut Microbiota Alteration Is Associated With Cognitive Deficits in Genetically Diabetic (Db/db) Mice During Aging
title_short Gut Microbiota Alteration Is Associated With Cognitive Deficits in Genetically Diabetic (Db/db) Mice During Aging
title_sort gut microbiota alteration is associated with cognitive deficits in genetically diabetic db db mice during aging
topic type 2 diabetes
cognitive dysfunction
gut microbiota
neuroinflammation
aging
url https://www.frontiersin.org/articles/10.3389/fnagi.2021.815562/full
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