Multi-biofluid Metabolomics as a Tool to Discover Metabolite Biomarkers for Cow’s Milk Allergy
E. De Paepe1 , L. Van Meulebroek1, V. Plekhova1, M. Van Winckel2, E. Cox3 and L. Vanhaecke1,4
In industrialized nations, food allergies are a growing epidemic and are considered a major thread to our wellbeing. Cow’s milk allergy (CMA) is one of the first allergies to occur in early childhood and early life sensitization has been associated with an increased risk to develop the atopic march later in life. As such, more research is urgently needed to gain more insights into this disease and to improve current diagnostics. Therefore, this pilot study evaluated a unique multi-biofluid platform, applying UHPLC-Q-Orbitrap-HRMS for polar metabolic fingerprinting as well as the innovative LA-REIMS for rapid metabolomics screening. The use of urine and feces was preferred in this research, as these biofluids are readily available. Additionally, the fecal content is influenced by genes, diet, environment and microbiome, which is implicated in oral tolerance development and is known to differ according to allergy state. Metabolic fingerprinting and screening was applied on simultaneously collected fecal and urine samples from children, below the age of 5 years, with IgE mediated CMA, non-IgE mediated CMA and healthy controls. The established OPLS-DA (metabolic fingerprinting) and LDA (metabolic screening) models for feces, urine and the combination thereof were able to discriminate according to allergy state. Most biomarker candidates could be linked to other microbiome-related diseases, such as asthma, inflammatory bowel disease, and autism, while other metabolites could be associated to the immune system.
As such, several biomarker candidates and related pathways were suggested. Additionally, the innovative LA-REIMS technique can be considered an excellent rapid metabolomics screening methodology.
Affiliations
1 Ghent University, Faculty of Veterinary Medicine, Department of Veterinary Public Health and Food Safety, Laboratory of Chemical Analysis, Salisburylaan 133, BE-9820 Merelbeke, Belgium - Ellen.DePaepe@UGent.be
2 Ghent University, Faculty of Medicine and Health Sciences, Department of Internal Medicine and Pediatrics, C.
Heymanslaan 10, BE-9000 Ghent, Belgium
3 Ghent University, Faculty of Veterinary Medicine, Department of Parasitology, Virology and Immunology, Laboratory of Immunology, Salisburylaan 133, BE-9820 Merelbeke, Belgium
4 Institute for Global Food Security, School of Biological Sciences, Queen’s University, Belfast, Northern Ireland, United Kingdom