E-cigarette and vaping device use continue to rise, particularly in adolescents and young adults, but the safety of inhaling the multitude of chemicals within e-cigarette aerosols has been questioned. While several studies have evaluated vaping effects on the lungs and heart; effects on the gastrointestinal tract remain unknown. Using established murine models of acute (1 week) and chronic (3 month) daily e-cigarette aerosol inhalation, both with nicotine-containing and vehicle control e-liquids, murine colon transcriptomics and organoid co-culture models, we assessed the effects of e-cigarette use on the gut barrier and mucosal health. Histologic analyses revealed that chronic exposure to nicotine-free e-cigarette aerosols induced mucosal inflammation. Transcriptome analyses revealed that chronic, but not acute, nicotine-free e-cigarette use significantly reduced expression of tight junction markers, including occluding, and drove expression of pro-inflammatory cytokines. Exposure of murine and human enteroid-derived monolayers (EDMs) to nicotine-free e-cigarette aerosols alone, or in co-culture with invasive E. coli, confirmed that repetitive exposure was sufficient to recapitulate the key findings observed in vivo, i.e., barrier-disruption, downregulation of occludin, inflammation, and an accentuated risk of and response to bacterial infection. These data highlight an unexpected harmful effect of e-cigarette use on the gut barrier and pinpoint non-nicotine chemical components common across >90% of e-cigarette e-liquids as the source of harm. Given the ever-expanding importance of the integrity of the gut barrier for host fitness, and impact of gut mucosal inflammation on a multitude of chronic diseases, these findings are broadly relevant to medicine and public health.

中文翻译：

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电子烟危害肠道屏障并引发肠道炎症

电子烟和电子烟设备的使用在继续增加，尤其是在青少年和年轻人中，但是在电子烟气雾剂中吸入多种化学药品的安全性受到质疑。尽管有几项研究评估了对肺和心脏的雾化作用。对胃肠道的影响尚不清楚。使用已建立的急性（1周）和慢性（3个月）每日电子烟气雾吸入模型，含尼古丁和媒介物控制的电子液体，鼠结肠转录组学和类器官共培养模型，我们评估了电子烟对肠壁屏障和黏膜健康的影响。组织学分析表明，长期暴露于无尼古丁的电子烟气溶胶会引起粘膜炎症。转录组分析显示，慢性而非急性 不含尼古丁的电子烟的使用会显着降低紧密连接标记的表达，包括阻塞和促进促炎性细胞因子的表达。鼠和人肠源性单分子层（EDM）单独暴露于无尼古丁的电子烟气溶胶，或与侵入性大肠杆菌共培养时，证实重复暴露足以概括体内观察到的主要发现，即屏障破坏，闭合蛋白的下调，炎症以及细菌感染的风险和反应加剧。这些数据突显了使用电子烟对肠屏障的意外危害，并指出了超过90％的电子烟电子液体中常见的非尼古丁化学成分是伤害的来源。鉴于肠壁屏障的完整性对于宿主适应性的重要性日益提高，