Effects of Electronic Cigarettes on Oral Microbiome and Metabolome in 3D Tissue-Engineered Models: Comment

Dear Editor,

We would like to discuss ‘The Effects of Electronic Cigarettes on Oral Microbiome and Metabolome in 3D Tissue-Engineered Models’.¹ Using an in vitro 3D organotypic model of the human oral mucosa, this study investigated the impact of e-cigarette (EC) aerosol exposure on the oral microbiota and oral metabolome. Although the methods and approach are commendable, some areas require more debate to increase the study's comprehension and impact. First, while 3D tissue-engineered models give a realistic picture of the human oral mucosa, it is unknown how well these models replicate the intricacies and long-term repercussions of chronic EC usage. Model duration, exposure frequency, and simulating real-world environmental elements such as nutrition and other oral hygiene routines may be of little significance to frequent EC users. Furthermore, while inoculation with saliva from healthy donors is intriguing, it does not capture the entire diversity of microbial communities between individuals, including those with oral disorders, or between smokers and nonsmokers.

The interpretation of changed metabolic profiles and microbial populations is a major topic of discussion. ECs with strong nicotine group flavours exhibit alpha diversity, which suggests alterations in the microbial makeup. However, what wider ramifications result from this shift in diversity? Does it reflect a robust microbiome that adjusts to external stressors like EC exposure, or is it connected to gut microbial dysbiosis, which is frequently linked to health issues like EC? High-nicotine flavours belonging to the EC13 nicotine group. The metabolic results that reveal nicotine metabolites offer important information about the possible negative effects of nicotine. Nevertheless, it is unclear which precise mechanisms cause the upregulation of metabolites linked to the development of oral cancer. This begs the question of whether these findings point to greater systemic effects that go beyond the oral cavity and may influence other organ systems.

This study's uniqueness stems from the use of a sophisticated in vitro model that replicates EC exposure more realistically than typical cell culture models. We also link microbiome changes to metabolic profile, which has not been thoroughly studied in this context. To have a greater impact on this sector, future studies must validate these findings in in vivo models and human populations to boost their therapeutic significance. Furthermore, the study's scope could be expanded to include the effects of chronic exposure, different types of EC devices, and non-nicotine flavoured aerosols. Understanding the long-term effects of EC on the oral microbiome and the resultant influence on overall health, particularly in terms of oral cancer, should be a top priority.

Future studies may focus on methods to mitigate the harmful consequences of EC exposure, such as possible probiotic medicines and oral microbiota manipulation tools. Furthermore, greater research into the impacts of EC exposure and other lifestyle factors (such as food and alcohol consumption) may provide a more complete picture of ECs’ effects on dental health. Overall, this study raises broader questions regarding how ECs, which are becoming increasingly popular worldwide, affect the human microbiota and health, as well as how the systemic impacts and preventive measures of ECs might be considered. Further advancements are required.

Conflict of interest

No conflict is declared.