TY - JOUR
T1 - Effects of inhaled air pollution on markers of integrity, inflammation, and microbiota profiles of the intestines in Apolipoprotein E knockout mice
AU - Fitch, Megan N.
AU - Phillippi, Danielle
AU - Zhang, Yan
AU - Lucero, Jo Ann
AU - Pandey, Ravi S.
AU - Liu, June
AU - Brower, Jeremy
AU - Allen, Michael S.
AU - Campen, Matthew J.
AU - McDonald, Jacob D.
AU - Lund, Amie K.
N1 - Funding Information:
This work was supported by National Institute of Environmental Health Sciences at the National Institute of Health [ ES014639 to MJC.] for the animal exposures, and the University of North Texas Research Initiation Grant (RIG) [ GA93601 to A.K.L] for the DNA sequencing and tissue analysis. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Environmental Health Sciences . All procedures were approved by the Lovelace Respiratory Research Institute's Animal Care and Use Committee (Protocol # FY15-023A ) and conform to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1996).
Funding Information:
This work was supported by National Institute of Environmental Health Sciences at the National Institute of Health [ES014639 to MJC.] for the animal exposures, and the University of North Texas Research Initiation Grant (RIG) [GA93601 to A.K.L] for the DNA sequencing and tissue analysis. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Environmental Health Sciences.All procedures were approved by the Lovelace Respiratory Research Institute's Animal Care and Use Committee (Protocol # FY15-023A) and conform to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1996).
Funding Information:
Funding from grants received from the National Institute of Environmental Health Sciences at National Institute of Health and University of North Texas were used to conduct some of the exposures and studies described, herein; however, the authors declare no conflict of interest or financial gains to these entities associated with this publication.
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2020/2
Y1 - 2020/2
N2 - Air pollution exposure is known to contribute to the progression of cardiovascular disease (CVD) and there is increasing evidence that dysbiosis of the gut microbiome may also play a role in the pathogenesis of CVD, including atherosclerosis. To date, the effects of inhaled air pollution mixtures on the intestinal epithelial barrier (IEB), and microbiota profiles are not well characterized, especially in susceptible individuals with comorbidity. Thus, we investigated the effects of inhaled ubiquitous air-pollutants, wood-smoke (WS) and mixed diesel and gasoline vehicle exhaust (MVE) on alterations in the expression of markers of integrity, inflammation, and microbiota profiles in the intestine of atherosclerotic Apolipoprotein E knockout (ApoE−/-) mice. To do this, male 8 wk-old ApoE−/- mice, on a high-fat diet, were exposed to either MVE (300 μg/m3 PM), WS; (∼450 μg/m3 PM), or filtered air (FA) for 6 h/d, 7 d/wk, for 50 d. Immunofluorescence and RT-PCR were used to quantify the expression of IEB components and inflammatory factors, including mucin (Muc)-2, tight junction (TJ) proteins, matrix metalloproteinase (MMP)-9, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β, as well as Toll-like receptor (TLR)-4. Microbial profiling of the intestine was done using Illumina 16S sequencing of V4 16S rRNA PCR amplicons. We observed a decrease in intestinal Muc2 and TJ proteins in both MVE and WS exposures, compared to FA controls, associated with a significant increase in MMP-9, TLR-4, and inflammatory marker expression. Both WS and MVE-exposure resulted in decreased intestinal bacterial diversity, as well as alterations in microbiota profiles, including the Firmicutes: Bacteroidetes ratio at the phylum level. Our findings suggest inhalation exposure to either MVE or WS result in alterations in components involved in mucosal integrity, and also microbiota profiles and diversity, which are associated with increased markers of an inflammatory response.
AB - Air pollution exposure is known to contribute to the progression of cardiovascular disease (CVD) and there is increasing evidence that dysbiosis of the gut microbiome may also play a role in the pathogenesis of CVD, including atherosclerosis. To date, the effects of inhaled air pollution mixtures on the intestinal epithelial barrier (IEB), and microbiota profiles are not well characterized, especially in susceptible individuals with comorbidity. Thus, we investigated the effects of inhaled ubiquitous air-pollutants, wood-smoke (WS) and mixed diesel and gasoline vehicle exhaust (MVE) on alterations in the expression of markers of integrity, inflammation, and microbiota profiles in the intestine of atherosclerotic Apolipoprotein E knockout (ApoE−/-) mice. To do this, male 8 wk-old ApoE−/- mice, on a high-fat diet, were exposed to either MVE (300 μg/m3 PM), WS; (∼450 μg/m3 PM), or filtered air (FA) for 6 h/d, 7 d/wk, for 50 d. Immunofluorescence and RT-PCR were used to quantify the expression of IEB components and inflammatory factors, including mucin (Muc)-2, tight junction (TJ) proteins, matrix metalloproteinase (MMP)-9, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β, as well as Toll-like receptor (TLR)-4. Microbial profiling of the intestine was done using Illumina 16S sequencing of V4 16S rRNA PCR amplicons. We observed a decrease in intestinal Muc2 and TJ proteins in both MVE and WS exposures, compared to FA controls, associated with a significant increase in MMP-9, TLR-4, and inflammatory marker expression. Both WS and MVE-exposure resulted in decreased intestinal bacterial diversity, as well as alterations in microbiota profiles, including the Firmicutes: Bacteroidetes ratio at the phylum level. Our findings suggest inhalation exposure to either MVE or WS result in alterations in components involved in mucosal integrity, and also microbiota profiles and diversity, which are associated with increased markers of an inflammatory response.
KW - Air pollution
KW - Inflammation
KW - Intestine epithelial barrier
KW - Microbiome
UR - http://www.scopus.com/inward/record.url?scp=85075505086&partnerID=8YFLogxK
U2 - 10.1016/j.envres.2019.108913
DO - 10.1016/j.envres.2019.108913
M3 - Article
C2 - 31753468
AN - SCOPUS:85075505086
SN - 0013-9351
VL - 181
JO - Environmental Research
JF - Environmental Research
M1 - 108913
ER -