Tracking gluten immunoreactive peptides from the grain to the gut and beyond

Wheat is one of the pillars for nutrition security worldwide, but the prevalence of wheat-related disorders (WRD) is increasing. Taken together, coeliac disease, non-coeliac gluten sensitivity and wheat food allergy may affect up to 10% of European individuals. The causes for this increase are still unknown, but involve the intricate interaction of proteolytically resistant gluten immunoreactive peptides (GIP) from wheat, rye and barley, the human immune system and yet unknown adjuvants. Total GIP can be detected by immunoassays in human plasma, urine and faeces (biosamples) after gluten consumption, but the precise molecular structures have not been clarified so far, because specific analytical methods are missing.The project GLUTENOMICS aims to elucidate the molecular structures of GIP in human biosamples and analyse factors determining their identities and quantities. I aim to achieve this using a combination of different approaches to overcome the analytical challenges by i) creating a comprehensive database of GIP and elucidating factors affecting gluten protein digestibility, ii) developing and validating proteomics methods to detect GIP in human biosamples and iii) establishing relations between the GIP profile of raw materials, foods and human biosamples. My central hypothesis is that gluten structure and content determine its digestibility which, in turn, leads to different GIP profiles in biosamples from healthy individuals and WRD patients. The unique toolbox of methods that I will put in place will provide a fundamentally new understanding of how protein structures govern digestibility and how the resulting peptides pass through the human digestive system. My ambition is to use the findings to tailor grain-based foods towards better tolerability to prevent the initial onset of WRD. Beyond grains, GLUTENOMICS opens significant innovative potential to promote human health through systematically structured, isolated or designed dietary proteins.