A. meyeri did not present in any group except the orally inoculated A. meyeri group. Furthermore, N. elongata presented in the stool samples from some mice after oral inoculation, but was not significantly elevated compared to the controls; elevation of A. meyeri instool after oral inoculation was extremely limited . These results indicate that A. meyeri may not be an oral commensal bacteriumin B6 mice, but it can colonize well on the surface of the oralcavity during oral inoculation. Long-term cannabis users may suffer disturbed brain connectivity,cognitive impairment, and psychological disorders , but the exactme chanisms are not fully understood. In the current study, we found that chronic cannabis use correlated with alterations of several taxa of the oral microbiome. A. meyeri was highly enriched in the saliva from chronic cannabis smokers compared to those of non-smokers,and oral enrichment of A. meyeri was associated with the age of first cannabis use. We further investigated if direct administration of this bacterium, in the absence of cannabis or the psychoactive THC component,could elicit alteration in the brain-immune axis in a mouse model. Long-term oral inoculation of A. meyeri bacteriumto mice resulted in behavioral changes, macrophage infiltration into the brain, and increased Ab 42 protein production in the brain.

Oral flora plays a role in maintaining oral health; however, environmental changes can result in dysbiosis vertical grow rack. Prior results have shown tobacco smoking alter the oral microbiome . Decreased abundance of Neisseria and Capnocytophaga and increased abundance of Streptococcus were found in tobacco smokers compared with those of non-smokers . Consistent with these findings, here wefound that the abundance of Neisseria, Capnocytophaga, and Cardiobacteriumgenera was reduced and the abundance of Streptococcus was increased in cannabis smokers compared to non-smokers. In contrast, cannabis use was associated with increases in the genera,Actinomyces, Atopobium, Megasphaera, and Veillonella. A previous study demonstrated a strikingly similarity in the physical and chemical properties produced by cannabis and tobacco smoking, which contained large amounts of hydrocarbon and changed the acidity of saliva . Thus, Streptococcus and Actinomyces, acid-tolerant and facultative anaerobes, may preferentially grow in a smoking-mediated environment. In contrast, bacteria such as Neisseria sp. and Corynebacteriumsp. were decreased in cannabis smokers, suggesting that smoking renders an unfavorable environment to facultative or strictanaerobes.

Although some oral microbiome is shared between tobacco smokers  and cannabis smokers, including increased Streptococcus and decreased Neisseria genus bacteria compared to non-smokers, A. meyeri was only increased in cannabis smokers.Moreover, the younger the age of first cannabis use, the more A.meyeri was orally enriched.Although the gut microbiome has been shown to play a crucialrole in the CNS activities via the bidirectional gut-brain axis ,strong connections between the oral microbiome and the CNS havebeen reported as well. P. gingivalis, a key pathogen in chronic periodontitis was identified to contribute to Alzheimer’s disease .Besides P. gingivalis, other oral resident microbes were shown to associate with neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease . Moreover, oral bacteria Treponema and N. meningitidis can infect the brain through the trigeminal or olfactory nerve cannabis grow racks. The perturbations of intestinal microbiota resulted in the impairment of memory formation and cognition in the hippocampus . To test the effect of cannabis use-associated oral dysbiosis on CNS functions, we performed various behavioral tests in mice following bacteria oral inoculations but did not observe significant memory changes.

Some Actinomyces species are commensal bacteria in the skin, oral, gut, and vagina of humans , but can also become opportunistic pathogens leading to infections in the dental cavity and other systemic sites . A. meyeri is associated with brain infection or dysfunction , but the causality and mechanisms of A. meyeri-mediated CNS dysfunction have never been reported. In this study, A. meyeri enrichment in the oral microbiome was inversely correlated with the age of first cannabis use, which indicates that the longer duration of cannabis exposure, the more enrichment of A.meyeri in the oral cavity. A previous study found younger age of first cannabis use was associated with decreased orbital prefrontal cortex volume . Another study found negative correlations between the age of initiation of cannabis use and altered thickness of the right superior frontal gyrus . Our study implies that the age of first cannabis use may be critical for particular oral microbiome development and its potential impact on cognitive function.