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

Abstract

Cigarette smoke (CS)-induced inflammation leads to a range of diseases including chronic obstructive pulmonary disease and cancer. Environmental factors including gut microbiota make up are major modifying factors that determine the severity of cigarette smoke-induced pathology. Adult zebrafish display increased inflammatory cytokine transcription when exposed to cigarette smoke extract (CSE) but incongruously do not produce a mucosal leukocytic inflammation phenotype. 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. Here we exposed zebrafish larvae to CSE and showed that it was toxic and we characterised a CSE-induced leukocytic inflammatory phenotype with increased neutrophilic and macrophage responses. 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. 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.