Abstract
BackgroundThe gut microbiota plays a vital role in host homeostasis and is associated with inflammation and cardiovascular disease (CVD) risk. Exposure to particulate matter (PM) is a known mediator of inflammation and CVD and is reported to promote dysbiosis and decreased intestinal integrity. However, the role of inhaled traffic-generated PM on the gut microbiome and its corresponding systemic effects are not well-characterized. Thus, we investigated the hypothesis that exposure to inhaled diesel exhaust particles (DEP) alters the gut microbiome and promotes microbial-related inflammation and CVD biomarkers. 4–6-week-old male C57Bl/6 mice on either a low-fat (LF, 10% fat) or high-fat (HF, 45% fat) diet were exposed via oropharyngeal aspiration to 35 μg DEP suspended in 35 μl saline or saline only (CON) 2x/week for 30 days. To determine whether probiotics could prevent diet or DEP exposure mediated alterations in the gut microbiome or systemic outcomes, a subset of animals on the HF diet were treated orally with 0.3 g/day (~ 7.5 × 108 CFU/day) of Winclove Ecologic® Barrier probiotics throughout the study.ResultsOur results show that inhaled DEP exposure alters gut microbial profiles, including reducing Actinobacteria and expanding Verrucomicrobia and Proteobacteria. We observed increased circulating LPS, altered circulating cytokines (IL-1α, IL-3, IL-13, IL-15, G-CSF, LIF, MIP-2, and TNF-α), and CVD biomarkers (siCAM, PAI-1, sP-Selectin, thrombomodulin, and PECAM) in DEP-exposed and/or HF diet mice. Furthermore, probiotics attenuated the observed reduction of Actinobacteria and expansion of Proteobacteria in DEP-exposed and HF-diet mice. Probiotics mitigated circulating cytokines (IL-3, IL-13, G-CSF, RANTES, and TNF- α) and CVD biomarkers (siCAM, PAI-1, sP-Selectin, thrombomodulin, and PECAM) in respect to DEP-exposure and/or HF diet.ConclusionKey findings of this study are that inhaled DEP exposure alters small intestinal microbial profiles that play a role in systemic inflammation and early CVD biomarkers. Probiotic treatment in this study was fundamental in understanding the role of inhaled DEP on the microbiome and related systemic inflammatory and CVD biomarkers.
Highlights
The gut microbiota is a dynamic group of microorganisms that plays a pivotal role in the homeostasis of its host by providing nutrients, providing protection fromPhillippi et al Particle and Fibre Toxicology (2022) 19:10 infections, stimulating the immune system, and aiding in digestion, among others [1]
Exposure to inhaled diesel exhaust particles (DEP) and a high‐fat diet results in altered cardiovascular disease biomarkers in cardiac tissue in male C57Bl/6 mice As systemic inflammation is associated with the pathogenesis of CVD, we investigated whether inhaled DEP exposure altered CVD biomarkers in cardiac tissue
Our findings demonstrate that inhaled DEP exposure alters the gut microbial profiles and diversity, increases systemic inflammatory response, and is implicated in the etiology of the early stages of CVD
Summary
The gut microbiota is a dynamic group of microorganisms that plays a pivotal role in the homeostasis of its host by providing nutrients, providing protection fromPhillippi et al Particle and Fibre Toxicology (2022) 19:10 infections, stimulating the immune system, and aiding in digestion, among others [1]. Exposure to air pollutants, such as particulate matter (PM), has been shown to alter the gut microbiome composition, increase the risk of obesity, gastrointestinal disorders, inflammation, cardiovascular disease (CVD), and other chronic illnesses [3,4,5,6,7,8,9]. Epidemiological studies have shown an increased incidence of hospitalization on days of high air pollution due to gastrointestinal distress, such as inflammatory bowel disease, ulcerative colitis, and Chron’s disease [10,11,12] These correlations emphasize a need to investigate further and characterize the effects of PM on the gut microbiome. To determine whether probiotics could prevent diet or DEP exposure mediated alterations in the gut microbiome or systemic outcomes, a subset of animals on the HF diet were treated orally with 0.3 g/day (~ 7.5 × 108 CFU/day) of Winclove Ecologic® Barrier probiotics throughout the study
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