Chronic cannabis smoking-enriched oral pathobiont drives behavioral changes, macrophage infiltration, and increases β-amyloid protein production in the brain

Background: Little is known about chronic cannabis smoking-associated oral microbiome and its effects on central nervous system (CNS) functions. Methods: In the current study, we have analyzed the saliva microbiome in individuals who chronically smoked cannabis with cannabis use disorder (n = 16) an...

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Autores principales: Zhenwu Luo, Sylvia Fitting, Catrina Robinson, Andreana Benitez, Min Li, Yongxia Wu, Xiaoyu Fu, Davide Amato, Wangbin Ning, Nicholas Funderburg, Xu Wang, Zejun Zhou, Xuezhong Yu, Amanda Wagner, Xiaomei Cong, Wanli Xu, Kendra Maas, Bethany J. Wolf, Lei Huang, Jeremy Yu, Alison Scott, Aimee Mcrae-Clark, Eric D. Hamlett, Wei Jiang
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Publicado: Elsevier 2021
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Acceso en línea:https://doaj.org/article/1efa300385834349ae3f982625ed84e1
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spelling oai:doaj.org-article:1efa300385834349ae3f982625ed84e12021-11-24T04:31:57ZChronic cannabis smoking-enriched oral pathobiont drives behavioral changes, macrophage infiltration, and increases β-amyloid protein production in the brain2352-396410.1016/j.ebiom.2021.103701https://doaj.org/article/1efa300385834349ae3f982625ed84e12021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2352396421004953https://doaj.org/toc/2352-3964Background: Little is known about chronic cannabis smoking-associated oral microbiome and its effects on central nervous system (CNS) functions. Methods: In the current study, we have analyzed the saliva microbiome in individuals who chronically smoked cannabis with cannabis use disorder (n = 16) and in non-smoking controls (n = 27). The saliva microbiome was analyzed using microbial 16S rRNA sequencing. To investigate the function of cannabis use-associated oral microbiome, mice were orally inoculated with live Actinomyces meyeri, Actinomyces odontolyticus, or Neisseria elongata twice per week for six months, which mimicked human conditions. Findings: We found that cannabis smoking in humans was associated with oral microbial dysbiosis. The most increased oral bacteria were Streptococcus and Actinomyces genus and the most decreased bacteria were Neisseria genus in chronic cannabis smokers compared to those in non-smokers. Among the distinct species bacteria in cannabis smokers, the enrichment of Actinomyces meyeri was inversely associated with the age of first cannabis smoking. Strikingly, oral exposure of Actinomyces meyeri, an oral pathobiont, but not the other two control bacteria, decreased global activity, increased macrophage infiltration, and increased β-amyloid 42 protein production in the mouse brains. Interpretation: This is the first study to reveal that long-term oral cannabis exposure is associated oral enrichment of Actinomyces meyeri and its contributions to CNS abnormalities.Zhenwu LuoSylvia FittingCatrina RobinsonAndreana BenitezMin LiYongxia WuXiaoyu FuDavide AmatoWangbin NingNicholas FunderburgXu WangZejun ZhouXuezhong YuAmanda WagnerXiaomei CongWanli XuKendra MaasBethany J. WolfLei HuangJeremy YuAlison ScottAimee Mcrae-ClarkEric D. HamlettWei JiangElsevierarticleCannabis smokingOral microbiomeActinomyces meyeriβ-amyloidMedicineRMedicine (General)R5-920ENEBioMedicine, Vol 74, Iss , Pp 103701- (2021)
institution DOAJ
collection DOAJ
language EN
topic Cannabis smoking
Oral microbiome
Actinomyces meyeri
β-amyloid
Medicine
R
Medicine (General)
R5-920
spellingShingle Cannabis smoking
Oral microbiome
Actinomyces meyeri
β-amyloid
Medicine
R
Medicine (General)
R5-920
Zhenwu Luo
Sylvia Fitting
Catrina Robinson
Andreana Benitez
Min Li
Yongxia Wu
Xiaoyu Fu
Davide Amato
Wangbin Ning
Nicholas Funderburg
Xu Wang
Zejun Zhou
Xuezhong Yu
Amanda Wagner
Xiaomei Cong
Wanli Xu
Kendra Maas
Bethany J. Wolf
Lei Huang
Jeremy Yu
Alison Scott
Aimee Mcrae-Clark
Eric D. Hamlett
Wei Jiang
Chronic cannabis smoking-enriched oral pathobiont drives behavioral changes, macrophage infiltration, and increases β-amyloid protein production in the brain
description Background: Little is known about chronic cannabis smoking-associated oral microbiome and its effects on central nervous system (CNS) functions. Methods: In the current study, we have analyzed the saliva microbiome in individuals who chronically smoked cannabis with cannabis use disorder (n = 16) and in non-smoking controls (n = 27). The saliva microbiome was analyzed using microbial 16S rRNA sequencing. To investigate the function of cannabis use-associated oral microbiome, mice were orally inoculated with live Actinomyces meyeri, Actinomyces odontolyticus, or Neisseria elongata twice per week for six months, which mimicked human conditions. Findings: We found that cannabis smoking in humans was associated with oral microbial dysbiosis. The most increased oral bacteria were Streptococcus and Actinomyces genus and the most decreased bacteria were Neisseria genus in chronic cannabis smokers compared to those in non-smokers. Among the distinct species bacteria in cannabis smokers, the enrichment of Actinomyces meyeri was inversely associated with the age of first cannabis smoking. Strikingly, oral exposure of Actinomyces meyeri, an oral pathobiont, but not the other two control bacteria, decreased global activity, increased macrophage infiltration, and increased β-amyloid 42 protein production in the mouse brains. Interpretation: This is the first study to reveal that long-term oral cannabis exposure is associated oral enrichment of Actinomyces meyeri and its contributions to CNS abnormalities.
format article
author Zhenwu Luo
Sylvia Fitting
Catrina Robinson
Andreana Benitez
Min Li
Yongxia Wu
Xiaoyu Fu
Davide Amato
Wangbin Ning
Nicholas Funderburg
Xu Wang
Zejun Zhou
Xuezhong Yu
Amanda Wagner
Xiaomei Cong
Wanli Xu
Kendra Maas
Bethany J. Wolf
Lei Huang
Jeremy Yu
Alison Scott
Aimee Mcrae-Clark
Eric D. Hamlett
Wei Jiang
author_facet Zhenwu Luo
Sylvia Fitting
Catrina Robinson
Andreana Benitez
Min Li
Yongxia Wu
Xiaoyu Fu
Davide Amato
Wangbin Ning
Nicholas Funderburg
Xu Wang
Zejun Zhou
Xuezhong Yu
Amanda Wagner
Xiaomei Cong
Wanli Xu
Kendra Maas
Bethany J. Wolf
Lei Huang
Jeremy Yu
Alison Scott
Aimee Mcrae-Clark
Eric D. Hamlett
Wei Jiang
author_sort Zhenwu Luo
title Chronic cannabis smoking-enriched oral pathobiont drives behavioral changes, macrophage infiltration, and increases β-amyloid protein production in the brain
title_short Chronic cannabis smoking-enriched oral pathobiont drives behavioral changes, macrophage infiltration, and increases β-amyloid protein production in the brain
title_full Chronic cannabis smoking-enriched oral pathobiont drives behavioral changes, macrophage infiltration, and increases β-amyloid protein production in the brain
title_fullStr Chronic cannabis smoking-enriched oral pathobiont drives behavioral changes, macrophage infiltration, and increases β-amyloid protein production in the brain
title_full_unstemmed Chronic cannabis smoking-enriched oral pathobiont drives behavioral changes, macrophage infiltration, and increases β-amyloid protein production in the brain
title_sort chronic cannabis smoking-enriched oral pathobiont drives behavioral changes, macrophage infiltration, and increases β-amyloid protein production in the brain
publisher Elsevier
publishDate 2021
url https://doaj.org/article/1efa300385834349ae3f982625ed84e1
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