Exposure to diesel exhaust particles results in altered lung microbial profiles, associated with increased reactive oxygen species/reactive nitrogen species and inflammation, in C57Bl/6 wildtype mice on a high-fat diet

Abstract

Background Exposure to traffic-generated emissions is associated with the development and exacerbation of inflammatory lung disorders such as chronic obstructive pulmonary disorder (COPD) and idiopathic pulmonary fibrosis (IPF). Although many lung diseases show an expansion of Proteobacteria, the role of traffic-generated particulate matter pollutants on the lung microbiota has not been well-characterized. Thus, we investigated the hypothesis that exposure to diesel exhaust particles (DEP) can alter commensal lung microbiota, thereby promoting alterations in the lung’s immune and inflammatory responses. We aimed to understand whether diet might also contribute to the alteration of the commensal lung microbiome, either alone or related to exposure. To do this, we used male C57Bl/6 mice (4–6-week-old) on either regular chow (LF) or high-fat (HF) diet (45% kcal fat), randomly assigned to be exposed via oropharyngeal aspiration to 35 μg DEP, suspended in 35 μl 0.9% sterile saline or sterile saline only (control) twice a week for 30 days. A separate group of study animals on the HF diet was concurrently treated with 0.3 g/day of Winclove Ecologic® Barrier probiotics in their drinking water throughout the study. Results Our results show that DEP-exposure increases lung tumor necrosis factor (TNF)-α, interleukin (IL)-10, Toll-like receptor (TLR)-2, TLR-4, and the nuclear factor kappa B (NF-κB) histologically and by RT-qPCR, as well as Immunoglobulin A (IgA) and Immunoglobulin G (IgG) in the bronchoalveolar lavage fluid (BALF), as quantified by ELISA. We also observed an increase in macrophage infiltration and peroxynitrite, a marker of reactive oxygen species (ROS) + reactive nitrogen species (RNS), immunofluorescence staining in the lungs of DEP-exposed and HF-diet animals, which was further exacerbated by concurrent DEP-exposure and HF-diet consumption. Histological examinations revealed enhanced inflammation and collagen deposition in the lungs DEP-exposed mice, regardless of diet. We observed an expansion of Proteobacteria, by qPCR of bacterial 16S rRNA, in the BALF of DEP-exposed mice on the HF diet, which was diminished with probiotic-treatment. Conclusions Our findings suggest that exposure to DEP causes persistent and sustained inflammation and bacterial alterations in a ROS-RNS mediated fashion, which is exacerbated by concurrent consumption of an HF diet.

Inhaled diesel exhaust particles result in microbiome-related systemic inflammation and altered cardiovascular disease biomarkers in C57Bl/6 male mice

“…16 ). We have previously reported that inhaled DEP exposure from these same study animals resulted in a significant expansion of Proteobacteria within the lungs, associated with inflammation and oxidative stress, which was attenuated through probiotic treatment [ 46 ]. Considering the exacerbated responses to DEP exposure in the HF diet animals, we decided to use a probiotic treatment in this study group to determine if we could mitigate the exposure and diet-mediated alterations in microbiota profiles and systemic responses.…”

“…However, there was an increase in two gram-negative genera within Proteobacteria phyla, Pseudomonas, and Delftia , in addition to Bacteroidetes, which could serve as a source of LPS. Importantly, the levels of LPS in the NIST DEP material used for these studies was previously measured by our laboratory and determined to be negligible; thus, it is not likely to be a contributing source of circulating LPS [ 46 ]. Probiotic treatment reduced systemic LPS levels in the HF + DEP group; however, there is no reduction of Proteobacteria compared to HF + CON.…”

“…1996). The authors note that the animals in this exposure and probiotic treatment study are the same animals from Daniel et al [ 46 ].…”

Effects and Mechanisms of Probiotics, Prebiotics, Synbiotics, and Postbiotics on Metabolic Diseases Targeting Gut Microbiota: A Narrative Review

“…Metabolic impairment is a common complication of nervous system dysfunction like Alzheimer's disease and depression [147,148]. A clinical trial on 60 patients with Alzheimer's disease showed that a 12-week intake of probiotic milk containing Bifidobacterium bifidum, Lactobacillus acidophilus, Lactobacillus casei, and Lactobacillus fermentum at a dose of 200 mL/day (2 × 10 9 CFU/g for each) improved cognitive function and metabolic status [127].…”

Air Pollution and the Airways: Lessons from a Century of Human Urbanization

“…More specifically, combining DEP and allergens, IL-33 is increased in lung tissue leading to Th2 inflammation and airway hyperreactivity which is completely reversed in ST2-deficient mice [140][141][142]. DEP can activate the respiratory epithelium via TLR2 and TLR4 leading to increased levels of TNF-α, NF-κB signaling pathway and NLRP3 inflammasome resulting in macrophage and neutrophil infiltration in the airways [143,144]. Furthermore, TNF-α has been shown to have a regulatory role in the induction of DEP pulmonary inflammation with the help of the TNFR2 receptor [145].…”