E-cigarettes compromise the gut barrier and trigger inflammation
Aditi Sharma,
Jasper Lee,
Ayden G. Fonseca,
Alex Moshensky,
Taha Kothari,
Ibrahim M. Sayed,
Stella-Rita Ibeawuchi,
Rama F. Pranadinata,
Jason Ear,
Debashis Sahoo,
Laura E. Crotty-Alexander,
Pradipta Ghosh,
Soumita Das
Affiliations
Aditi Sharma
Department of Pathology, University of California, San Diego, CA 92093, USA
Jasper Lee
Department of Pathology, University of California, San Diego, CA 92093, USA
Ayden G. Fonseca
Department of Cellular and Molecular Medicine, University of California, San Diego, CA 92093, USA
Alex Moshensky
Department of Medicine, University of California, San Diego, CA 92093, USA
Taha Kothari
Department of Pathology, University of California, San Diego, CA 92093, USA
Ibrahim M. Sayed
Department of Pathology, University of California, San Diego, CA 92093, USA
Stella-Rita Ibeawuchi
Department of Pathology, University of California, San Diego, CA 92093, USA
Rama F. Pranadinata
Department of Cellular and Molecular Medicine, University of California, San Diego, CA 92093, USA
Jason Ear
Department of Cellular and Molecular Medicine, University of California, San Diego, CA 92093, USA; Department of Medicine, University of California, San Diego, CA 92093, USA
Debashis Sahoo
Department of Pediatrics, University of California, San Diego, CA 92093, USA; Department of Computer Science and Engineering, Jacobs School of Engineering, University of California, San Diego, CA 92093, USA; Rebecca and John Moore Comprehensive Cancer Center, University of California, San Diego, CA 92093, USA
Laura E. Crotty-Alexander
Department of Medicine, University of California, San Diego, CA 92093, USA; Veterans Affairs Medical Center, VA San Diego Healthcare System, La Jolla, San Diego, CA 92093, USA; Corresponding author
Pradipta Ghosh
Department of Cellular and Molecular Medicine, University of California, San Diego, CA 92093, USA; Department of Medicine, University of California, San Diego, CA 92093, USA; Rebecca and John Moore Comprehensive Cancer Center, University of California, San Diego, CA 92093, USA; Veterans Affairs Medical Center, VA San Diego Healthcare System, La Jolla, San Diego, CA 92093, USA; Corresponding author
Soumita Das
Department of Pathology, University of California, San Diego, CA 92093, USA; Rebecca and John Moore Comprehensive Cancer Center, University of California, San Diego, CA 92093, USA; Corresponding author
Summary: E-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.
