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A systematic review and pathway mapping of metabolic alterations underlying food allergy

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Abstract
INTRODUCTION IgE-mediated food allergies (IgE-FA) are characterized by an ever-increasing prevalence, currently reaching up to 10.4% of children in the European Union. In recent years, metabolomics has surfaced as an expedient technology in the field of biomarker discovery and pathophysiological pathway elucidation, as it provides a snapshot of the functional phenotype of an individual. Indeed, metabolomics is a highly promising technique to provide a deeper understanding into the pathogenic mechanisms behind IgE-FA, which is imperative to bolster the discovery of improved diagnostic and prognostic biomarkers as well as novel treatment strategies. MATERIALS AND METHODS In this work, literature was systematically searched using Web of Science, PubMed, Scopus and Embase, from January 2010 until May 2021 including human and animal metabolomic studies on multiple biofluids (urine, blood, feces). In total, 15 studies on IgE-FA were retained and a database of 277 potential biomarkers was compiled for in-depth pathway mapping. RESULTS AND DISCUSSION This systematic review revealed alterations in carbohydrate and energy metabolism, as well as lipid, amino acid, nucleotide and microbial metabolism. With respect to the energy metabolism in IgE-FA children, a pronounced shift towards aerobic glycolysis was evinced, arising as a direct metabolic consequence of dysbiosis. The switch towards glycolytic pathways was even more emphasized in animal models of anaphylaxis, which was combined with a shift towards ketogenesis. Lipid changes in blood, including the synthesis of sphingolipids, were suggested as indicator of severity, i.e. history of anaphylaxis, pointing towards a hyperresponsive mast cell state. Differences in lipid allergy mediators, such as choline and its metabolites, suggested increased PAF synthesis during anaphylaxis. Decreased IDO-1 activity was hypothesized due to altered plasma levels of tryptophan and its metabolites in IgE-FA children, thereby creating a Th2-skewed immune environment. A dysregulated purine pathway was considered critical for allergic sensitization and anaphylaxis, with increased levels of uric acid hinting towards an (a)symptomatic state of underlying inflammation. In feces of children prior to IgE-FA development, aberrant metabolization of sphingolipids and histidine was noted. Differences in microbial metabolites, i.e. SCFAs and bile acids pointed towards a combination of altered microbial and host metabolic activity. CONCLUSIONS To conclude, this work suggested several pathway alterations in case of IgE-FA and, thereby offered a solid basis for future research. In this regard, it confirms the unprecedented opportunities of metabolomics and supports the in-depth pathophysiological qualification in the quest towards improved diagnostic and prognostic biomarkers for IgE-FA.
Keywords
Systematic Review, Metabolomics, Food Allergy

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MLA
De Paepe, Ellen, et al. “A Systematic Review and Pathway Mapping of Metabolic Alterations Underlying Food Allergy.” NuGO Week, Book of Abstracts, 2021.
APA
De Paepe, E., Van Gijseghem, L., De Spiegeleer, M., Cox, E., & Vanhaecke, L. (2021). A systematic review and pathway mapping of metabolic alterations underlying food allergy. NuGO Week, Book of Abstracts. Presented at the eNuGO Week 2021, online.
Chicago author-date
De Paepe, Ellen, Lynn Van Gijseghem, Margot De Spiegeleer, Eric Cox, and Lynn Vanhaecke. 2021. “A Systematic Review and Pathway Mapping of Metabolic Alterations Underlying Food Allergy.” In NuGO Week, Book of Abstracts.
Chicago author-date (all authors)
De Paepe, Ellen, Lynn Van Gijseghem, Margot De Spiegeleer, Eric Cox, and Lynn Vanhaecke. 2021. “A Systematic Review and Pathway Mapping of Metabolic Alterations Underlying Food Allergy.” In NuGO Week, Book of Abstracts.
Vancouver
1.
De Paepe E, Van Gijseghem L, De Spiegeleer M, Cox E, Vanhaecke L. A systematic review and pathway mapping of metabolic alterations underlying food allergy. In: NuGO Week, Book of abstracts. 2021.
IEEE
[1]
E. De Paepe, L. Van Gijseghem, M. De Spiegeleer, E. Cox, and L. Vanhaecke, “A systematic review and pathway mapping of metabolic alterations underlying food allergy,” in NuGO Week, Book of abstracts, online, 2021.
@inproceedings{8744016,
  abstract     = {{INTRODUCTION
IgE-mediated food allergies (IgE-FA) are characterized by an ever-increasing prevalence, currently reaching up to 10.4% of children in the European Union. In recent years, metabolomics has surfaced as an expedient technology in the field of biomarker discovery and pathophysiological pathway elucidation, as it provides a snapshot of the functional phenotype of an individual. Indeed, metabolomics is a highly promising technique to provide a deeper understanding into the pathogenic mechanisms behind IgE-FA, which is imperative to bolster the discovery of improved diagnostic and prognostic biomarkers as well as novel treatment strategies. 

MATERIALS AND METHODS
In this work, literature was systematically searched using Web of Science, PubMed, Scopus and Embase, from January 2010 until May 2021 including human and animal metabolomic studies on multiple biofluids (urine, blood, feces). In total, 15 studies on IgE-FA were retained and a database of 277 potential biomarkers was compiled for in-depth pathway mapping.

RESULTS AND DISCUSSION
This systematic review revealed alterations in carbohydrate and energy metabolism, as well as lipid, amino acid, nucleotide and microbial metabolism. With respect to the energy metabolism in IgE-FA children, a pronounced shift towards aerobic glycolysis was evinced, arising as a direct metabolic consequence of dysbiosis. The switch towards glycolytic pathways was even more emphasized in animal models of anaphylaxis, which was combined with a shift towards ketogenesis. Lipid changes in blood, including the synthesis of sphingolipids, were suggested as indicator of severity, i.e. history of anaphylaxis, pointing towards a hyperresponsive mast cell state. Differences in lipid allergy mediators, such as choline and its metabolites, suggested increased PAF synthesis during anaphylaxis. Decreased IDO-1 activity was hypothesized due to altered plasma levels of tryptophan and its metabolites in IgE-FA children, thereby creating a Th2-skewed immune environment. A dysregulated purine pathway was considered critical for allergic sensitization and anaphylaxis, with increased levels of uric acid hinting towards an (a)symptomatic state of underlying inflammation. In feces of children prior to IgE-FA development, aberrant metabolization of sphingolipids and histidine was noted. Differences in microbial metabolites, i.e. SCFAs and bile acids pointed towards a combination of altered microbial and host metabolic activity.

CONCLUSIONS
To conclude, this work suggested several pathway alterations in case of IgE-FA and, thereby offered a solid basis for future research. In this regard, it confirms the unprecedented opportunities of metabolomics and supports the in-depth pathophysiological qualification in the quest towards improved diagnostic and prognostic biomarkers for IgE-FA.}},
  author       = {{De Paepe, Ellen and Van Gijseghem, Lynn and De Spiegeleer, Margot and Cox, Eric and Vanhaecke, Lynn}},
  booktitle    = {{NuGO Week, Book of abstracts}},
  keywords     = {{Systematic Review,Metabolomics,Food Allergy}},
  language     = {{eng}},
  location     = {{online}},
  title        = {{A systematic review and pathway mapping of metabolic alterations underlying food allergy}},
  year         = {{2021}},
}