Chronic cannabis smoking-enriched oral pathobiont drives behavioral changes, macrophage infiltration, and increases β-amyloid protein production in the brain.
Amyloid beta-Peptides
/ metabolism
Animals
Bacteria
/ classification
Brain
/ metabolism
Case-Control Studies
Cell Line
DNA, Bacterial
/ genetics
DNA, Ribosomal
/ genetics
Disease Models, Animal
Female
Humans
Macrophages
/ metabolism
Marijuana Smoking
/ immunology
Mice
Phylogeny
RNA, Ribosomal, 16S
/ genetics
Saliva
/ microbiology
Sequence Analysis, DNA
Actinomyces meyeri
Cannabis smoking
Oral microbiome
β-amyloid
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Dec 2021
Dec 2021
Historique:
received:
10
08
2021
revised:
24
10
2021
accepted:
03
11
2021
pubmed:
27
11
2021
medline:
22
3
2022
entrez:
26
11
2021
Statut:
ppublish
Résumé
Little is known about chronic cannabis smoking-associated oral microbiome and its effects on central nervous system (CNS) functions. 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. 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. 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.
Sections du résumé
BACKGROUND
BACKGROUND
Little is known about chronic cannabis smoking-associated oral microbiome and its effects on central nervous system (CNS) functions.
METHODS
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
RESULTS
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
CONCLUSIONS
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.
Identifiants
pubmed: 34826801
pii: S2352-3964(21)00495-3
doi: 10.1016/j.ebiom.2021.103701
pmc: PMC8626580
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
DNA, Bacterial
0
DNA, Ribosomal
0
RNA, Ribosomal, 16S
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
103701Subventions
Organisme : NIA NIH HHS
ID : R21 AG074331
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD096501
Pays : United States
Organisme : NIDA NIH HHS
ID : K24 DA038240
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG054159
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA045596
Pays : United States
Organisme : NIA NIH HHS
ID : K23 AG044434
Pays : United States
Organisme : NIGMS NIH HHS
ID : U54 GM104941
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS099595
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001450
Pays : United States
Organisme : NINR NIH HHS
ID : P20 NR016605
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR072582
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM109040
Pays : United States
Organisme : NINR NIH HHS
ID : R01 NR016928
Pays : United States
Informations de copyright
Copyright © 2021. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare no competing interests.