Intranasal Exposure to Hog Dust Extract Promotes Endotoxemia and Increases Gene Expression of TNF‐α and Secretary Epithelial Cell Markers in Mouse Intestine

Abstract

Agriculture‐related dust exposures to antimicrobial‐resistant pathogens can have significant health implications for animal agricultural industry workers. In addition to major respiratory complications, air pollutants provoke intestinal diseases and altered digestive tract physiology. Hog farm dust is highly abundant in gram‐positive and gram‐negative bacteria. Lipopolysaccharides (LPS; endotoxins) excised from gram‐negative bacteria can drive increased intestinal permeability and inflammation. Therefore, we hypothesized that acute intranasal exposure to aqueous extracts of dusts collected from hog confinement facilities (HDE) ‐ containing bacterial LPS ‐ cause increased intestinal inflammation and barrier dysfunction. We previously showed that intranasal exposure of 8‐week‐old male or female C57BL/6J mice (n=12) to 12.5% HDE (containing 22.1‐91.1 EU/mL) (n=6) for 3 weeks elevated bronchoalveolar lavage total cell and neutrophil levels (indicative of chronic airway inflammation), and increased intestinal permeability, in comparison to saline controls (n=6). We now report that HDE‐treated mice have elevated serum LPS levels (unpaired t‐test, p<0.0001; n=6/group) suggesting endotoxemia. To further identify intestinal epithelial responses initiated by HDE, inflammatory genes were examined in intestinal whole tissue lysates by qPCR. TNF‐α expression was increased in the ileum (unpaired t‐test, p=0.0265; n=3‐5/group) but not in the colon of HDE‐treated mice. Conversely, IL‐1B, IL‐6 and IL‐10 were not significantly altered along the intestinal tract. Following HDE treatment, mRNA expression of the goblet cell marker, Muc2, was increased in distal colon epithelial cells (unpaired t‐test, p=0.0099, n=3‐5/group). The Paneth cell‐associated marker, Lyz1 (lysozyme), was unchanged in ileum but was increased in proximal colon epithelial cells (p=0.0444, n=2‐5/group) of HDE‐treated mice. Collectively, these data indicate that agricultural dust exposure induces endotoxemia and promotes intestinal inflammation characterized by increased TNF‐α and host anti‐microbial responses.