Exposure to the gut microbiota from cigarette smoke-exposed mice exacerbates cigarette smoke extract-induced inflammation in zebrafish larvae

Simone Morris; Kathryn Wright; Vamshikrishna Malyla; Warwick J Britton; Philip M Hansbro; Pradeep Manuneedhi Cholan; Stefan H Oehlers

doi:10.1016/j.crimmu.2021.12.001

Exposure to the gut microbiota from cigarette smoke-exposed mice exacerbates cigarette smoke extract-induced inflammation in zebrafish larvae

Curr Res Immunol. 2021 Dec 6:2:229-236. doi: 10.1016/j.crimmu.2021.12.001. eCollection 2021.

Authors

Simone Morris¹, Kathryn Wright¹, Vamshikrishna Malyla^{2

3}, Warwick J Britton^{1

4}, Philip M Hansbro², Pradeep Manuneedhi Cholan¹, Stefan H Oehlers^{1

5}

Affiliations

¹ Tuberculosis Research Program at the Centenary Institute, The University of Sydney, Camperdown, NSW, Australia.
² Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW, Australia.
³ Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW, Australia.
⁴ Department of Clinical Immunology, Royal Prince Alfred Hospital, Camperdown, Australia.
⁵ The University of Sydney, Faculty of Medicine and Health, Camperdown, NSW, Australia.

Abstract

Cigarette smoke (CS)-induced inflammation leads to a range of diseases including chronic obstructive pulmonary disease and cancer. The gut microbiota is a major modifying environmental factor that determine the severity of cigarette smoke-induced pathology. Microbiomes and metabolites from CS-exposed mice exacerbate lung inflammation via the gut-lung axis of shared mucosal immunity in mice but these systems are expensive to establish and analyse. Zebrafish embryos and larvae have been used to model the effects of cigarette smoking on a range of physiological processes and offer an amenable platform for screening modifiers of cigarette smoke-induced pathologies with key features of low cost and rapid visual readouts. Here we exposed zebrafish larvae to cigarette smoke extract (CSE) and characterised a CSE-induced leukocytic inflammatory phenotype with increased neutrophilic and macrophage inflammation in the gut. The CSE-induced phenotype was exacerbated by co-exposure to microbiota from the faeces of CS-exposed mice, but not control mice. Microbiota could be recovered from the gut of zebrafish and studied in isolation in a screening setting. This demonstrates the utility of the zebrafish-CSE exposure platform for identifying environmental modifiers of cigarette smoking-associated pathology and demonstrates that the CS-exposed mouse gut microbiota potentiates the inflammatory effects of CSE across host species.

Keywords: Cigarette smoke; Enterocolitis; Microbiota; Zebrafish.