Fig. 16

Proposed mechanism of inhaled DEP and HF diet on the gut microbiome, systemic inflammation, and CVD biomarkers. DEP from the lungs can affect the gut by indirect effects by absorption through the lungs into circulation or by direct effect via mucociliary clearance and subsequent ingestion and entry into the gastrointestinal tract. Systemic responses increase inflammation and cytokine signaling via granulocyte colony-stimulating factor (G-CSF), tumor necrosis factor alpha (TNF-α), interleukin (IL)-1α, and IL-3, which can stress the gut causing alterations in the gut microbiome. Alterations in the gut microbiome associated with inhaled DEP exposure include decreased Actinobacteria and expansion of Proteobacteria, Verrucomicrobia, and Bacteroidetes, which could likely be the source of lipopolysaccharide (LPS) infiltration into circulation further exacerbating inflammatory cytokine concentration in circulation. The overall increase in DEP osure mediated systemic inflammation results in the early concentration of cardiovascular disease (CVD) biomarkers such as thrombomodulin, soluble intracellular adhesion molecule (sICAM), and soluble platelet selection (sP-selectin). This persistent change in microbial profiles and inflammation is a possible contributor to DEP-mediated CVD