BACKGROUND: Dietary carbohydrates and fats are intrinsically correlated within the habitual diet. We aimed to disentangle the associations of starch and sucrose from those of fat, in relation to allergic sensitization, asthma and rhinoconjuctivitis prevalence in humans, and to investigate underlying mechanisms using murine models. METHODS: Epidemiological data from participants of two German birth cohorts (age 15) were used in logistic regression analyses testing cross-sectional associations of starch and sucrose (and their main dietary sources) with aeroallergen sensitization, asthma and rhinoconjunctivitis, adjusting for correlated fats (saturated, monounsaturated, omega-6 and omega-3 polyunsaturated) and other covariates. For mechanistic insights, murine models of aeroallergen-induced allergic airway inflammation (AAI) fed with a low-fat-high-sucrose or -high-starch versus a high-fat diet were used to characterize and quantify disease development. Metabolic and physiologic parameters were used to track outcomes of dietary interventions and cellular and molecular responses to monitor the development of AAI. Oxidative stress biomarkers were measured in murine sera or lung homogenates. RESULTS: We demonstrate a direct association of dietary sucrose with asthma prevalence in males, while starch was associated with higher asthma prevalence in females. In mice, high-carbohydrate feeding, despite scant metabolic effects, aggravated AAI compared to high-fat in both sexes, as displayed by humoral response, mucus hypersecretion, lung inflammatory cell infiltration and TH 2-TH 17 profiles. Compared to high-fat, high-carbohydrate intake was associated with increased pulmonary oxidative stress, signals of metabolic switch to glycolysis and decreased systemic anti-oxidative capacity. CONCLUSION: High consumption of digestible carbohydrates is associated with an increased prevalence of asthma in humans and aggravated lung allergic inflammation in mice, involving oxidative stress-related mechanisms.

Center of Allergy and Environment and Helmholtz Zentrum München German Research Center for Environmental Health Munich Germany

Chair of Experimental Genetics TUM School of Life Sciences Technische Universität München Freising Germany

Czech Centre for Phenogenomics Institute of Molecular Genetics of the Czech Academy of Sciences Průmyslová 595 252 50 Vestec Czech Republic

Department of Environmental Immunology Helmholtz Centre for Environmental Research UFZ Leipzig Germany

Department of Medicine Technical University of Munich Munich Germany

Department of Pediatrics Gastroenterology and Nutrition School of Medicine Collegium Medicum University of Warmia and Mazury Olsztyn Poland

Department of Pediatrics Technical University of Munich Munich Germany

Dr von Hauner Children's Hospital University Hospital LMU of Munich Munich Germany

German Center for Diabetes Research Neuherberg Germany

German Center of Lung Research Munich Germany

Institute of Epidemiology Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany

Institute of Experimental Genetics German Mouse Clinic Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany

Institute of Lung Biology and Disease Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany

Institute of Medical Biochemistry Biocenter Medical University of Innsbruck Innsbruck Austria

Institute of Molecular Animal Breeding and Biotechnology Gene Center Ludwig Maximilians University Munich Munich Germany

IUF Leibniz Research Institute for Environmental Medicine Düsseldorf Germany

Research Institute Department of Pediatrics Marien Hospital Wesel Wesel Germany

RG Adipocytes and Metabolism Institute for Diabetes and Obesity Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany

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$a BACKGROUND: Dietary carbohydrates and fats are intrinsically correlated within the habitual diet. We aimed to disentangle the associations of starch and sucrose from those of fat, in relation to allergic sensitization, asthma and rhinoconjuctivitis prevalence in humans, and to investigate underlying mechanisms using murine models. METHODS: Epidemiological data from participants of two German birth cohorts (age 15) were used in logistic regression analyses testing cross-sectional associations of starch and sucrose (and their main dietary sources) with aeroallergen sensitization, asthma and rhinoconjunctivitis, adjusting for correlated fats (saturated, monounsaturated, omega-6 and omega-3 polyunsaturated) and other covariates. For mechanistic insights, murine models of aeroallergen-induced allergic airway inflammation (AAI) fed with a low-fat-high-sucrose or -high-starch versus a high-fat diet were used to characterize and quantify disease development. Metabolic and physiologic parameters were used to track outcomes of dietary interventions and cellular and molecular responses to monitor the development of AAI. Oxidative stress biomarkers were measured in murine sera or lung homogenates. RESULTS: We demonstrate a direct association of dietary sucrose with asthma prevalence in males, while starch was associated with higher asthma prevalence in females. In mice, high-carbohydrate feeding, despite scant metabolic effects, aggravated AAI compared to high-fat in both sexes, as displayed by humoral response, mucus hypersecretion, lung inflammatory cell infiltration and TH 2-TH 17 profiles. Compared to high-fat, high-carbohydrate intake was associated with increased pulmonary oxidative stress, signals of metabolic switch to glycolysis and decreased systemic anti-oxidative capacity. CONCLUSION: High consumption of digestible carbohydrates is associated with an increased prevalence of asthma in humans and aggravated lung allergic inflammation in mice, involving oxidative stress-related mechanisms.

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