Dietary Intervention in Food Allergy: Microbiome, Epigenetic and Metabolomic interactions
|Partner Organization||Partner Country|
|Universidad San Pablo CEU||Spain|
|University Regional Hospital Center of Nancy||France|
1. Overall project description
Cumulative evidence suggests that food allergy (FA) is associated with a multitude of environmental factors including hygiene habits, antibiotic use, lifestyle changes and, in particular, diet. Changes in nutrition can result in dysbiosis of the skin, gut, and lung microbiota and generate changes in microbial the metabolites produced, which may in turn produce epigenetic modifications. Current evidence supports the view that epigenetic mechanisms are involved in immune regulation and may represent a key-missing piece of the etiological puzzle for FA, at the interface between the environment and the genome. Dietary fibre can change the gut microbiota composition and therefore cause epigenome changes promoting health. Pectin is one type of dietary fibre that can exert immune regulation and mouse studies have shown its capability to prevent and even cure respiratory allergies.
DIFAMEM aims to investigate the effects of FA treatment through intervention with a prebiotic dietary component, pectin, and using peach allergy as a model.
This project will advance our understanding on how the interaction between dietary components and gut microbiota composition leads to epigenetic changes that provoke the immune modulation, and establish new strategies for dietary intervention in FA, with potential applications for other immune-related diseases.During this year, we have got important advances regarding the identification of the optimal pectin type using an established peach allergy model. Moreover, we have been able to confirm that although pectins due to the fruit sources can contain LTP, the amounts are under the threshold to induce anaphylactic reactions in nsLTP-allergic patients. Additionally, the intervention study has been finalised and the different biological samples distributed to the partners in charged on the different omic analysis, microbiome, epigenomic, metabolomics and immunologic analysis. Moreover, the analysis of the clinical outcomes is now ongoing.
- The peach allergy mouse model has been established with homogenous sensitisation. It has been demonstrated by the induction of clinical signs (e.g. drop of body temperature) and the increase in levels of antigen-specific (nPru p3) IgE, IgG1 and IgG2a titers. Moreover, an increase in mMCPT-1 (a mast cell activation marker) levels in the intestinal homogenates also suggests an involvement of the gut in the response.
- Pectins used as dietary fiber are extracted from citrus or apple pomace containing several allergens such as non-specific lipid transfer proteins (nsLTPs). This could be important for allergic patients to this food allergen. Then we have analysed the residual nsLTP content in two commercial pectins using different detection methods and demonstrated that the potential residual allergen content in both pectins is below the threshold to induce anaphylactic reactions in nsLTP-allergic patients. This data suggests that consumption of the investigated commercial pectin products do not pose a risk for inducing severe reactions in nsLTP-allergic patients.
- The intervention study has been completed in 37 patients allergic to LTP. After opening the blind, it was observed an induction of tolerance of Pru p 3 in 31% and 33% in patients treated with Active 1 and Active 2 respectively with only 11% of tolerance induction in placebo group. No changes in the wheal size with SPT to Pru p 3 or serum Pru p 3 sIgE levels have been found.
- Related to liver safety, there are no changes in all liver and other metabolic determination after the intervention study.
- Epigenomic studies in experimental mice through the analysis of top hypo-hyper methylated CpGs sites in three levels (20 %, 15% and 10% of methylation difference) indicates that there are more differentially methylated CpGs following to exposure to CU901 comparing to Herbapekt at the same concentration and there are more differentially methylated CpGs at higher concentration (15%) compared to the low concentration (5%) of each type of pectin.
4.1 List of publications
|Authors||Title||Year, Issue, PP||Partners Number||Doi|
|Steigerwald H*, Blanco-Perez F*, Albrecht M*, Bender C, Wangorsch A, Endreß HU, Bunzel M, Mayorga C*, Torres MJ*, Scheurer S*, Vieths S*.||Does the Food Ingredient Pectin Provide a Risk for Patients Allergic to Non-Specific Lipid-Transfer Proteins? (2021, Dec 21, 11(1):13)||2021, Dec 21, 11(1):13||2||10.3390/foods11010013||Download|
4.2 Presentation of the project
4.3 List of submitted patents and other outputs
|Patent licence||Partners involved||Year||International eu or national patent||Comment|