Exposure to non-microbial N -Glycolylneuraminic acid protects farmers’ children against airway inflammation and colitis

Abstract Background Childhood exposure to a farm environment has been shown to protect against the development of inflammatory diseases such as allergy, asthma, and inflammatory bowel disease. Objective We sought to investigate whether besides exposure to microbes also exposure to structures of non-microbial origin such as the sialic acid N -Glycolylneuraminic acid (Neu5Gc) may play a significant role. Methods Exposure to Neu5Gc was evaluated by quantifying anti-Neu5Gc antibody levels in the sera of children enrolled in two farm studies: the PARSIFAL study (n=299) and the PASTURE birth cohort (cord blood (n=836), 1 year (n=734), 4.5 years (n=700) and 6 years (n=728)), and we associated them with asthma and wheeze. The effect of Neu5Gc was examined in murine airway inflammation and colitis models and the role of Neu5Gc in regulating immune activation was assessed by T helper cells and regulatory T cell activation in mice. Results In children, anti-Neu5Gc IgG levels positively correlated with living on a farm and increased peripheral blood Foxp3 expression and inversely correlated with wheezing and asthma in non-atopic subjects. Exposure to Neu5Gc in mice resulted in reduced airway hyperresponsiveness and inflammatory cell recruitment to the lung. Furthermore, Neu5Gc administration to mice reduced the severity of a colitis model. Mechanistically, we found that Neu5Gc exposure reduced IL-17 positive T cells and supported differentiation of regulatory T cells. Conclusions In addition to microbial exposure, increased exposure to non-microbial-derived Neu5Gc may contribute to the protective effects associated with the farm environment.