Effects Of Ambient Particulate Matter On Lung And Gut Microbial In Rat And Its Role In The Pathogenesis Of COPD

Background Particulate matter(PM)refers to an air-suspended mixture of pollutants,which contains a complex mixture of smoke,dust,and other solid and liquid materials,as well as numerous biological components.Inhaled ambient PM represents important environmental exposures that have been linked to death and disease.Emerging epidemiological evidence also suggests that these exposures increase the risks of respiratory diseases.Research on PM has mostly focused on the lung inflammatory response to inhalation,as this is considered the primary impact of PM exposure.Recent studies have linked changes in the lung microbiome to human disease,but the effects of PM on the lung microbiome are largely unknown.Though research on PM has mostly focused on the lung inflammatory response to inhalation,as this is considered the primary impact of PM exposure.However,PM also enter the gut directly through the lungs by mucocilliary transport or through the ingestion of foods coated with PM.These findings suggest that the steady state concentrations of PM in the gut may be similar to those encountered in the lung.Emerging evidence suggests PM exposure can also have adverse consequences on the gut.In addition,studies have shown that changes in microbial composition and function in the gut were recently linked to alterations in immune responses and to disease development in the lungs,emerging pathogenic links between microbiota and the gut-lung axis.This indicates that there is a vital cross-talk between these two mucosal sites,but effects of the microbiota and gut-lung axis in the pathogenesis of COPD after chronic ambient PM exposure are largely unknown.In summary,characterizing which microbial communities and functions are influenced by or influence exposure to PM may lead to new insights of how PM leads to COPD.Objective To observe the effect of ambient particulate matter on lung and intestinal microbial composition.Exploring the potential mechanism of the gut-lung axis in COPD caused by PM.Methods and results Part I Exposure to ambient particulate matter alters the microbial composition in rat lung.Methods: Fifty-seven Sprague-Dawley rats were randomly divided into clean air(CON),biomass fuel(BMF),and motor vehicle exhaust(MVE)groups.After a 4-week exposure,the microbial composition of the lung was assessed by 16 S rRNA pyrosequencing,the structure of the lung tissue was assessed with histological analysis,the phagocytic response of alveolar macrophages to bacteria was determined by flow cytometry,and immunoglobulin concentrations were measured with commercial ELISA kits.Results: There was no significant difference in lung morphology between the groups.However,the BMF and MVE groups displayed greater bacterial abundance and diversity.Proteobacteria were present in higher proportions in the MVE group,and 12 bacterial families differed in their relative abundances between the three groups.In addition,particulate matter exposure significantly increased the capacity of alveolar macrophages to phagocytose bacteria and induced changes in immunoglobulin levels.Part II An alteration of the gut-lung axis drives chronic obstructive pulmonary disease after chronic ambient particulate matter exposure.Methods: Fifty-four male Sprague-Dawley rats(7-9 weeks in age)were randomly divided into clean air(CON),biomass fuel(BMF),and motor vehicle exhaust(MVE)groups.Rats were exposed at 1-months,3-months and 6-months times points respectively.Subsequently,the structure of the lung tissue was assessed with histological analysis,the microbial composition of the ileal was assessed by 16 S rRNA pyrosequencing,the level of serum LPS in rats were measured and quantification of short chain fatty acids(SCFAs)in cecal contents.Results: After a 6-months exposure,PM(BMF/MVE)exposure induce COPD-like characteristic pathological changes and pulmonary inflammation in rats.The PM(BMF/MVE)exposure groups displayed greater bacterial abundance at 1-months and 3-months times points.There was no significant difference in bacterial diversity between the three groups during PM exposure at 1-months,3-months and 6-months times points respectively.Proteobacteria were present in higher proportions in the MVE group after 1-months exposure,but decrease after 6-months exposure.After 6-months exposure,level of serum LPS in PM(BMF/MVE)exposure groups were increased,level of SCFAs in ileal contents were decreased.Conclusion: 1.We demonstrated that particulate matter exposure can alter the microbial composition and change the pulmonary immunologic homeostasis in the rat lung.2.Chronic exposure to ambient particulate matter induces the intestinal microbial shifts and translocation,the gut-lung axis plays an integral part in the pathogenic mechanisms underlying the pathogenesis of COPD.