Dietary digestible carbohydrates are associated with higher prevalence of asthma in humans and with aggravated lung allergic inflammation in mice

BackgroundDietary 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. MethodsEpidemiological 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. ResultsWe 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 T(H)2-T(H)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. ConclusionHigh 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.

Automated summary

This study investigated the association between starch, sucrose, and fat in relation to allergic sensitization and asthma prevalence in humans, as well as their underlying mechanisms using mouse models. The findings suggest that 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.