The reduction of DSS-induced colitis severity in mice exposed to cigarette smoke is linked to immune modulation and microbial shifts

Giuseppe Lo Sasso,Emmanuel Guedj,Sonia Ouadi,Manuel C Peitsch,David Bornand,Athanasios Kondylis,Ching Keong Tung,Maica Corciulo,Alain Sewer,Nikolai V Ivanov,Celine Merg,Blaine W Phillips,Julia Hoeng,Remi Dulize,Marja Talikka,Dariusz Peric,Bjoern Titz,Rendy Yanuar,James N D Battey

doi:10.1038/s41598-020-60175-3

Giuseppe Lo Sasso, Emmanuel Guedj + Show 17 more

Open Access

https://doi.org/10.1038/s41598-020-60175-3

Copy DOI

Abstract

Exposure to cigarette smoke (CS) causes detrimental health effects, increasing the risk of cardiovascular, pulmonary diseases and carcinogenesis in exposed individuals. The impact of CS on Inflammatory Bowel Disease (IBD) has been established by a number of epidemiological and clinical studies. In fact, CS is associated with a higher risk of developing Crohn’s disease (CD) while inversely correlates with the development, disease risks, and relapse rate of ulcerative colitis (UC). To investigate the effect of CS exposure on experimental colitis, we performed a comprehensive and integrated comparative analysis of colon transcriptome and microbiome in mice exposed to dextran sodium sulfate (DSS) and CS. Colon transcriptome analysis revealed that CS downregulated specific pathways in a concentration-dependent manner, affecting both the inflammatory state and composition of the gut microbiome. Metagenomics analysis demonstrated that CS can modulate DSS-induced dysbiosis of specific bacterial genera, contributing to resolve the inflammation or accelerate recovery. The risks of smoking far outweigh any possible benefit, thus smoking cessation must always be encouraged because of its significant health benefits. However, the inverse association between active smoking and the development of UC cannot be ignored and the present study lays the foundation for investigating potential molecular mechanisms responsible for the attenuation of colitis by certain compounds of tobacco when decoupled from combustion.

Highlights

Exposure to cigarette smoke (CS) causes detrimental health effects, increasing the risk of cardiovascular, pulmonary diseases and carcinogenesis in exposed individuals
Induced colitis, mice exposed to CS were treated with 2.5% dextran sodium sulfate (DSS) in drinking water for five days followed by one week of recovery without DSS (Fig. 1A,B)
Final average total particulate matter (TPM) values in the CS exposure chambers were 0 (−2.6 μg/L), 454.4 μg/L, 591.8 μg/L, and 744.6 μg/L, all within 5% of the target TPM concentrations (Fig. 1C). These TPM values corresponded to average nicotine concentrations of 0, 24.7 μg/L, 32.2 μg/L, and 40.0 μg/L, respectively (Fig. 1D)

Summary

Introduction

Exposure to cigarette smoke (CS) causes detrimental health effects, increasing the risk of cardiovascular, pulmonary diseases and carcinogenesis in exposed individuals. The inverse association between active smoking and the development of UC cannot be ignored and the present study lays the foundation for investigating potential molecular mechanisms responsible for the attenuation of colitis by certain compounds of tobacco when decoupled from combustion. No unique cause has been determined for IBD, but its etiopathogenesis is thought to arise from a genetic susceptibility to dysregulated interaction between immune factors and the enteric commensal flora Environmental triggers, such as drug use, stress, diet, and smoking, influence disease onset and development[4]. We combined a validated UC mouse model (dextran sulfate sodium, DSS) and a well-controlled inhalation exposure design with disease-specific endpoints and system-wide molecular profiling to investigate the effect of mainstream CS exposure on experimental colitis. Data acquired through this study highlight new molecular targets that may represent avenues for preventative strategies and support the potential to develop novel drugs

Methods

Results

Conclusion