Porphyromonas gingivalis-Induced Cognitive Impairment Is Associated With Gut Dysbiosis, Neuroinflammation, and Glymphatic Dysfunction
BackgroundPeriodontal pathogen and gut microbiota are closely associated with the pathogenesis of Alzheimer’s disease (AD). Porphyromonas gingivalis (Pg), the keystone periodontal pathogen, can induce cognitive impairment. The gut has a connection and communication with the brain, which is an import...
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2021
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oai:doaj.org-article:4c9f484286284ec9a1d9bccccf20c6832021-12-02T00:52:15ZPorphyromonas gingivalis-Induced Cognitive Impairment Is Associated With Gut Dysbiosis, Neuroinflammation, and Glymphatic Dysfunction2235-298810.3389/fcimb.2021.755925https://doaj.org/article/4c9f484286284ec9a1d9bccccf20c6832021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcimb.2021.755925/fullhttps://doaj.org/toc/2235-2988BackgroundPeriodontal pathogen and gut microbiota are closely associated with the pathogenesis of Alzheimer’s disease (AD). Porphyromonas gingivalis (Pg), the keystone periodontal pathogen, can induce cognitive impairment. The gut has a connection and communication with the brain, which is an important aspect of the gut–brain axis (GBA). In the present study, we investigate whether Pg induces cognitive impairment through disturbing the GBA.MethodsIn this study, Pg was orally administered to mice, three times a week for 1 month. The effects of Pg administration on the gut and brain were evaluated through behaviors, gut microbiota, immune cells, glymphatic pathway clearance, and neuroinflammation.ResultsPg induced cognitive impairment and dysbiosis of gut microbiota. The α-diversity parameters did not show significant change after Pg administration. The β-diversity demonstrated that the gut microbiota compositions were different between the Pg-administered and control groups. At the species level, the Pg group displayed a lower abundance of Parabacteroides gordonii and Ruminococcus callidus than the control group, but a higher abundance of Mucispirillum schaedleri. The proportions of lymphocytes in the periphery and myeloid cells infiltrating the brain were increased in Pg-treated animals. In addition, the solute clearance efficiency of the glymphatic system decreased. Neurons in the hippocampus and cortex regions were reduced in mice treated with Pg. Microglia, astrocytes, and apoptotic cells were increased. Furthermore, amyloid plaque appeared in the hippocampus and cortex regions in Pg-treated mice.ConclusionsThese findings indicate that Pg may play an important role in gut dysbiosis, neuroinflammation, and glymphatic system impairment, which may in turn lead to cognitive impairment.Li ChiXiao ChengLishan LinLishan LinTao YangJianbo SunYiwei FengFengyin LiangFengyin LiangZhong PeiZhong PeiWei TengFrontiers Media S.A.articlePorphyromonas gingivaliscognitive impairmentneuroinflammationglymphatic systemgut–brain axisMicrobiologyQR1-502ENFrontiers in Cellular and Infection Microbiology, Vol 11 (2021) |
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Porphyromonas gingivalis cognitive impairment neuroinflammation glymphatic system gut–brain axis Microbiology QR1-502 |
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Porphyromonas gingivalis cognitive impairment neuroinflammation glymphatic system gut–brain axis Microbiology QR1-502 Li Chi Xiao Cheng Lishan Lin Lishan Lin Tao Yang Jianbo Sun Yiwei Feng Fengyin Liang Fengyin Liang Zhong Pei Zhong Pei Wei Teng Porphyromonas gingivalis-Induced Cognitive Impairment Is Associated With Gut Dysbiosis, Neuroinflammation, and Glymphatic Dysfunction |
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BackgroundPeriodontal pathogen and gut microbiota are closely associated with the pathogenesis of Alzheimer’s disease (AD). Porphyromonas gingivalis (Pg), the keystone periodontal pathogen, can induce cognitive impairment. The gut has a connection and communication with the brain, which is an important aspect of the gut–brain axis (GBA). In the present study, we investigate whether Pg induces cognitive impairment through disturbing the GBA.MethodsIn this study, Pg was orally administered to mice, three times a week for 1 month. The effects of Pg administration on the gut and brain were evaluated through behaviors, gut microbiota, immune cells, glymphatic pathway clearance, and neuroinflammation.ResultsPg induced cognitive impairment and dysbiosis of gut microbiota. The α-diversity parameters did not show significant change after Pg administration. The β-diversity demonstrated that the gut microbiota compositions were different between the Pg-administered and control groups. At the species level, the Pg group displayed a lower abundance of Parabacteroides gordonii and Ruminococcus callidus than the control group, but a higher abundance of Mucispirillum schaedleri. The proportions of lymphocytes in the periphery and myeloid cells infiltrating the brain were increased in Pg-treated animals. In addition, the solute clearance efficiency of the glymphatic system decreased. Neurons in the hippocampus and cortex regions were reduced in mice treated with Pg. Microglia, astrocytes, and apoptotic cells were increased. Furthermore, amyloid plaque appeared in the hippocampus and cortex regions in Pg-treated mice.ConclusionsThese findings indicate that Pg may play an important role in gut dysbiosis, neuroinflammation, and glymphatic system impairment, which may in turn lead to cognitive impairment. |
format |
article |
author |
Li Chi Xiao Cheng Lishan Lin Lishan Lin Tao Yang Jianbo Sun Yiwei Feng Fengyin Liang Fengyin Liang Zhong Pei Zhong Pei Wei Teng |
author_facet |
Li Chi Xiao Cheng Lishan Lin Lishan Lin Tao Yang Jianbo Sun Yiwei Feng Fengyin Liang Fengyin Liang Zhong Pei Zhong Pei Wei Teng |
author_sort |
Li Chi |
title |
Porphyromonas gingivalis-Induced Cognitive Impairment Is Associated With Gut Dysbiosis, Neuroinflammation, and Glymphatic Dysfunction |
title_short |
Porphyromonas gingivalis-Induced Cognitive Impairment Is Associated With Gut Dysbiosis, Neuroinflammation, and Glymphatic Dysfunction |
title_full |
Porphyromonas gingivalis-Induced Cognitive Impairment Is Associated With Gut Dysbiosis, Neuroinflammation, and Glymphatic Dysfunction |
title_fullStr |
Porphyromonas gingivalis-Induced Cognitive Impairment Is Associated With Gut Dysbiosis, Neuroinflammation, and Glymphatic Dysfunction |
title_full_unstemmed |
Porphyromonas gingivalis-Induced Cognitive Impairment Is Associated With Gut Dysbiosis, Neuroinflammation, and Glymphatic Dysfunction |
title_sort |
porphyromonas gingivalis-induced cognitive impairment is associated with gut dysbiosis, neuroinflammation, and glymphatic dysfunction |
publisher |
Frontiers Media S.A. |
publishDate |
2021 |
url |
https://doaj.org/article/4c9f484286284ec9a1d9bccccf20c683 |
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