Exposure to nonmicrobial N-glycolylneuraminic acid protects farmers' children against airway inflammation and colitis.
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 both exposure to microbes and exposure to structures of nonmicrobial origin, such as the sialic acid N-glycolylneuraminic acid (Neu5Gc), might play a significant role.


METHODS
Exposure to Neu5Gc was evaluated by quantifying anti-Neu5Gc antibody levels in sera of children enrolled in 2 farm studies: the Prevention of Allergy Risk factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study (n = 299) and the Protection Against Allergy Study in Rural Environments (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 based on helper T-cell and regulatory T-cell activation in mice.


RESULTS
In children anti-Neu5Gc IgG levels correlated positively with living on a farm and increased peripheral blood forkhead box protein 3 expression and correlated inversely with wheezing and asthma in nonatopic 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+ T-cell numbers and supported differentiation of regulatory T cells.


CONCLUSIONS
In addition to microbial exposure, increased exposure to non-microbial-derived Neu5Gc might contribute to the protective effects associated with the farm environment.
['Frei|Remo|R|', 'Ferstl|Ruth|R|', 'Roduit|Caroline|C|', 'Ziegler|Mario|M|', 'Schiavi|Elisa|E|', 'Barcik|Weronika|W|', 'Rodriguez-Perez|Noelia|N|', 'Wirz|Oliver F|OF|', 'Wawrzyniak|Marcin|M|', 'Pugin|Benoit|B|', 'Nehrbass|Dirk|D|', 'Jutel|Marek|M|', 'Smolinska|Sylwia|S|', 'Konieczna|Patrycja|P|', 'Bieli|Christian|C|', 'Loeliger|Susanne|S|', 'Waser|Marco|M|', 'Pershagen|Göran|G|', 'Riedler|Josef|J|', 'Depner|Martin|M|', 'Schaub|Bianca|B|', 'Genuneit|Jon|J|', 'Renz|Harald|H|', 'Pekkanen|Juha|J|', 'Karvonen|Anne M|AM|', 'Dalphin|Jean-Charles|JC|', 'van Hage|Marianne|M|', 'Doekes|Gert|G|', 'Akdis|Mübeccel|M|', 'Braun-Fahrländer|Charlotte|C|', 'Akdis|Cezmi A|CA|', 'von Mutius|Erika|E|', "O'Mahony|Liam|L|", 'Lauener|Roger P|RP|', '|||', '|||']
D000367:Age Factors D000485:Allergens D000818:Animals D015415:Biomarkers D002648:Child D002675:Child, Preschool D003092:Colitis D003430:Cross-Sectional Studies D004195:Disease Models, Animal D004781:Environmental Exposure D000067565:Farmers D006801:Humans D007073:Immunoglobulin E D007074:Immunoglobulin G D007223:Infant D007249:Inflammation D008214:Lymphocytes D051379:Mice D018345:Mice, Knockout D009438:Neuraminic Acids D011159:Population Surveillance D012140:Respiratory Tract Diseases D012720:Severity of Illness Index D016176:T-Lymphocyte Subsets
nonmicrobial N-glycolylneuraminic acid Farmers' children airway inflammation colitis anti-inflammatory