UC San Diego

Rising levels of e-cigarette usage particularly among young adults have become a major cause for concern, considering mounting evidence against its reputation as a safe smoking alternative. Previous studies have shown that e-cigarette aerosols trigger inflammatory responses in the lungs and heart, but the full systemic effects of aerosolized components are unknown, particularly in the largest immune organ: the

intestinal tract. We investigated the impact of e-cigarettes on the intestine using established in vivo murine models of acute (1 week) and chronic (3 months) e-cigarette exposure, measuring their impact on the intestinal barrier and mucosal inflammation. Histologic analyses revealed that chronic exposure to nicotine-free e-cigarette aerosols induced mucosal inflammation, and transcript expression analyses revealed that chronic exposure to nicotine-free e-cigarette significantly reduced expression of intestinal barrier genes and increased expression of pro-inflammatory genes. Further experiments done with ex-vivo murine and human intestinal models were able to reproduce the same findings found in vivo, and allowed for co-culture experiments with invasive E.coli, demonstrating that chronic exposure to nicotine-free e-cigarette aerosol produces the most drastic tight junction disruption, and inflammatory signaling, as well as an increased risk of maladaptive response to bacterial infection. These results shed light on the previously unknown effects of e-cigarette aerosols on the intestinal barrier, identifying the non-nicotine components of e-cigarettes as the agent of inflammatory damage.