Introduction: Although having been introduced ten years ago, little is known of the impact of electronic nicotine delivery systems (ENDS) on human health. ENDS usage is rapidly rising among adolescents and young adults and this is partially due to a perception that ENDS are safer than cigarettes and nicotine replacement therapies. However, these products vary widely in nicotine content, propylene glycol, glycerol, additives and flavorings; all of which are poorly studied, and it is possible that may deliver toxins that interfere with a variety of bodily processes. Therefore, there is an urgent need for biological investigations that will improve our understanding of how ENDS impact human health. The initial point of contact of ENDS, and the first-affected system in humans is the oral cavity. It is known that nicotine adversely impacts oral health, acting as a cytotoxic agent and pro-inflammatory mediator, as well as negatively impacting the oral microbiome. Oral health is dependent upon an intricate balance between the microbial ecosystem and host immunity.
Objective: Based on our preliminary studies that ENDS alter the compositional structure and the functional potential of the oral ecosystem, we hypothesized that ENDS impacts this microbial-mucosal homeostasis. We tested this hypothesis by comparing host-microbial dynamics during de-novo colonization of the subgingival microbiome among systemically and periodontally healthy e-cigarette users and non-smoker healthy controls.
Methods: A 12-week prospective, case-control study was performed on 30 periodontally and systemically healthy subjects, with 10 e-cigarette users and 20 non-user controls. Plaque, gingival crevicular fluid, and saliva samples were obtained from both the groups at screening visit, after which oral prophylaxis was performed. Samples were collected 1, 2, 4, 7, 14, 21, 30, 60, 90 days after prophylaxis. The samples were subjected to whole genome shot gun sequencing and semi-quantitative targeted proteomics using a panel of 45 markers of human inflammation.
Results: At baseline, the microbial profiles of vapers and non-vapers differed significantly in composition and function (p<0.05, Adonis test of Bray Curtis Dissimilarity distance). Vapers also demonstrated significantly greater pro-inflammatory response, as evidenced by higher levels of PD-L1, IFN-β, TNF-β, IL-13, IL-17A, IL-17E, IL-13, IL-33, IL-7, and lower levels of IL-10. Following prophylaxis, the microbiomes of vapers differed significantly from pre-prophylaxis baselines for two weeks, following which, no differences could be detected. By contrast, controls did not differ from baseline until 90 days after prophylaxis. With respect to host-microbial interactions, both vapers and controls demonstrated robust networks anchored by cytokines. However, vapers demonstrated more numbers of congeneric hubs between cytokines and concomitantly lower numbers of inter-generic hubs between cytokines and bacteria than controls during all eleven visits.
Conclusion: Vaping alters the subgingival microbial ecosystem to a highly diverse, pathogen-rich, virulent community which elicits a robust pro-inflammatory response. Moreover, patterns of host-microbial interactions are disrupted in vapers in comparison to controls. Oral prophylaxis does not serve to mitigate the negative impact of vaping, with a return to dysbiosis and dysregulated homeostasis within two weeks. Further studies are needed to identify methods to mitigate the negative health effects of e-cigarettes.