Chronic cannabis smoking-enriched oral pathobiont drives behavioral changes, macrophage infiltration, and increases β-amyloid protein production in the brain
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
Affiliations
Zhenwu Luo
Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Ave., Charleston, SC 29425, USA
Sylvia Fitting
Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Catrina Robinson
Department of Neurology, Medical University of South Carolina, Charleston, SC 29425, USA
Andreana Benitez
Department of Neurology, Medical University of South Carolina, Charleston, SC 29425, USA
Min Li
Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Ave., Charleston, SC 29425, USA
Yongxia Wu
Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Ave., Charleston, SC 29425, USA
Xiaoyu Fu
Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Ave., Charleston, SC 29425, USA; Department of Infectious Disease, Key Laboratory of Hunan Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
Davide Amato
Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA
Wangbin Ning
Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Ave., Charleston, SC 29425, USA; Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
Nicholas Funderburg
Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, Ohio State University College of Medicine, Columbus, OH, USA
Xu Wang
Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Ave., Charleston, SC 29425, USA; Department of Urology, Capital Medical University Affiliated XuanWu Hospital, 45 Changchun Street, Xicheng District, Beijing 100053, China
Zejun Zhou
State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha 410081, China
Xuezhong Yu
Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Ave., Charleston, SC 29425, USA
Amanda Wagner
Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC 29425, USA
Xiaomei Cong
Department of Pediatrics, School of Medicine, School of Nursing, Institute for Systems Genomics, University of Connecticut, Storrs, CT, USA
Wanli Xu
Department of Pediatrics, School of Medicine, School of Nursing, Institute for Systems Genomics, University of Connecticut, Storrs, CT, USA
Kendra Maas
Microbial Analysis, Resources, and Services, University of Connecticut, Storrs, CT, USA
Bethany J. Wolf
Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC 29425, USA
Lei Huang
Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
Jeremy Yu
Department of Medicine, Division of Endocrinology, Diabetes and Metabolic Diseases, Medical University of South Carolina, Charleston, SC 29425, USA
Alison Scott
Department of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, MD 21201, USA
Aimee Mcrae-Clark
Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC 29425, USA
Eric D. Hamlett
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA; Corresponding author at: Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 171 Ashley Ave MSC908, Charleston, SC 29425, USA
Wei Jiang
Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Ave., Charleston, SC 29425, USA; Department of Medicine, Division of Infectious Diseases, Medical University of South Carolina, Charleston, SC 29425, USA; Corresponding author at: Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Ave., Charleston, SC 29425, USA.
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.
