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.
Experiment 1
Reviewed Marked as Reviewed by Atrayees on 2023-7-3
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Mus musculus
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Small intestine Anterior intestine,Intestinum tenue,Mid intestine,Small bowel,Small intestine,small intestine
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- mice exposed to Filtered Air
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- mice exposed to MVE
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- male ApoE−/- mice exposed to mixed diesel and gasoline engine emissions (MVE) or Wood Smoke (WS)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 20
- Group 1 sample size Number of subjects in the case (exposed) group
- 20
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V4
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- Kruskall-Wallis
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- decreased
- Richness Number of species
- decreased
Signature 1
Source: Figure 10 & text
Description: Effects of inhaled filtered air (FA), wood-smoke (WS), and mixed diesel and gasoline vehicle exhaust (MVE) on the relative abundance of gastrointestinal bacteria at the (A) phylum level, and (B) genus level in ApoE−/-mice.
Abundance in Group 1: increased abundance
in
mice exposed to MVE
NCBI | Quality Control | Links |
---|
Turicibacter | | |
Clostridium | | |
Bacillota | | |
Revision editor(s): WikiWorks,
Atrayees
Signature 2
Source: Figure 10 & text
Description: Effects of inhaled filtered air (FA), wood-smoke (WS), and mixed diesel and gasoline vehicle exhaust (MVE) on the relative abundance of gastrointestinal bacteria at the (A) phylum level, and (B) genus level in ApoE−/-mice.
Abundance in Group 1: decreased abundance
in
mice exposed to MVE
NCBI | Quality Control | Links |
---|
Lactobacillus | | |
Oscillospira | | |
unclassified Lachnospiraceae | | |
Revision editor(s): Claregrieve1,
WikiWorks
Experiment 2
Reviewed Marked as Reviewed by Atrayees on 2023-7-3
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- mice exposed to WS
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- decreased
- Richness Number of species
- decreased
Signature 1
Reviewed Marked as Reviewed by Atrayees on 2023-7-3
Source: Figure 10 & text
Description: Effects of inhaled filtered air (FA), wood-smoke (WS), and mixed diesel and gasoline vehicle exhaust (MVE) on the relative abundance of gastrointestinal bacteria at the (A) phylum level, and (B) genus level in ApoE−/-mice.
Abundance in Group 1: increased abundance
in
mice exposed to WS
NCBI | Quality Control | Links |
---|
Bacteroidales | | |
Revision editor(s): Claregrieve1,
WikiWorks
Signature 2
Reviewed Marked as Reviewed by Atrayees on 2023-7-3
Source: Figure 10 & text
Description: Effects of inhaled filtered air (FA), wood-smoke (WS), and mixed diesel and gasoline vehicle exhaust (MVE) on the relative abundance of gastrointestinal bacteria at the (A) phylum level, and (B) genus level in ApoE−/-mice.
Abundance in Group 1: decreased abundance
in
mice exposed to WS
NCBI | Quality Control | Links |
---|
Clostridium | | |
Lactobacillus | | |
Oscillospira | | |
unclassified Lachnospiraceae | | |
Revision editor(s): Claregrieve1,
WikiWorks