摘要:SummaryE-cigarette usage continues to rise, yet the safety of e-cigarette aerosols is questioned. Using murine models of acute and chronic e-cigarette aerosol inhalation, murine colon transcriptomics, and murine and human gut-derived organoids in co-culture models, we assessed the effects of e-cigarette use on the gut barrier. Histologic and transcriptome analyses revealed that chronic, but not acute, nicotine-free e-cigarette use increased inflammation and reduced expression of tight junction (TJ) markers. Exposure of murine and human enteroid-derived monolayers (EDMs) to nicotine-free e-cigarette aerosols alone or in co-culture with bacteria also causes barrier disruption, downregulation of TJ protein, and enhanced inflammation in response to infection. These data highlight the harmful effects of “non-nicotine” component of e-cigarettes on the gut barrier. Considering the importance of an intact gut barrier for host fitness and the impact of gut mucosal inflammation on a multitude of chronic diseases, these findings are broadly relevant to both medicine and public health.Graphical abstractDisplay OmittedHighlights•Chronic vaping disrupts the gut barrier and triggers inflammation•Transcriptome studies reveal the broad impact of e-cig on gut health•Enteroid monolayers reveal that e-liquid, not nicotine, is the culprit•Chronic exposure to e-cig increases susceptibility to bacterial infectionBiological Sciences; Physiology; Toxicology; Microbiology; Microbiome; Transcriptomics