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/m 3 PM), WS; (~450 μg/m 3 PM), or filtered air (FA) for 6 hr/d,
7d/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.