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 TH2‐TH17 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.
Epidemiological study discovers novel associations between high intake of dietary sucrose and starch with current asthma in males and females, respectively. High‐carbohydrate feeding in mice aggravates allergic outcomes: serum IgE, lung inflammatory cell infiltration, TH2‐ or TH2‐TH17 profiles and mucus hypersecretion. Dietary carbohydrate‐driven enhanced pulmonary oxidative stress and decreased systemic anti‐oxidative capacity are involved in this context.Abbreviations: APE, aqueous pollen extract; EOS, eosinophils; GINIplus, German Infant study on the Influence of Nutrition Intervention plus environmental and genetic influences on allergy development; HDM, house dust mite; IgE, immunoglobulin E; LISA, life‐style related factors on the development of the Immune System and Allergies in East and West Germany; M, macrophages; NEU, neutrophils; Th, T helper
Abstract
RNA-binding proteins (RBPs) are critical host factors for viral infection, however, large scale experimental investigation of the binding landscape of human RBPs to viral RNAs is costly and ...further complicated due to sequence variation between viral strains. To fill this gap, we investigated the role of RBPs in the context of SARS-CoV-2 by constructing the first in silico map of human RBP-viral RNA interactions at nucleotide-resolution using two deep learning methods (pysster and DeepRiPe) trained on data from CLIP-seq experiments on more than 100 human RBPs. We evaluated conservation of RBP binding between six other human pathogenic coronaviruses and identified sites of conserved and differential binding in the UTRs of SARS-CoV-1, SARS-CoV-2 and MERS. We scored the impact of mutations from 11 variants of concern on protein–RNA interaction, identifying a set of gain- and loss-of-binding events, as well as predicted the regulatory impact of putative future mutations. Lastly, we linked RBPs to functional, OMICs and COVID-19 patient data from other studies, and identified MBNL1, FTO and FXR2 RBPs as potential clinical biomarkers. Our results contribute towards a deeper understanding of how viruses hijack host cellular pathways and open new avenues for therapeutic intervention.
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