Research project
36 | monthsNUTRICEL

The impact of nutrition in the natural history of celiac disease

Related toSpoke 06

Principal investigators
Valentina Discepolo,Roberto Berni Canani,Lutgarda Bozzetto,Antonio Molinaro,Raffaele Capasso

Other partecipantsAntonella Marano, Franca Oglio, Serena Coppola
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Other partners

European Laboratory for the Investigation of Food Induced Diseases (ELFID)

Task involved

Task 6.1.1.

Profiling of vulnerable targets (in connection with SPOKE 5) through: a) analyses of existing data in children affected by obesity and ageing population at risk of malnutrition and non-communicable diseases (NCDs) b) screening of socioeconomic factors, lifestyle and dietary habits, environmental factors, food knowledge, nutritional status, body composition, functional status and disability, quality of life, genetic, metagenetic, phenotypic profiles, exposure to endocrine disruptors chemicals (EDCs), immune system functions in children and aging population with malnutrition c) human-derived biological samples analysis (including samples for the gut microbiome structure analysis and function).

Task 6.1.2.

Identification and application of biomarkers of malnutrition (including inflammatory, metabolic, microbiological, genetic and epigenetic ones) and biochemical pathways associated with diet and age-related diseases/ syndromes for early malnutrition detection and quality of life restoration in target specific categories.

Task 6.2.1.

Identification of sustainable tailored multidimensional approach including nutritional strategies aimed at reducing malnutrition in target specific populations by exploiting the interactions between environment, food, genotype and phenotype: a) analysis of the positive and negative interactions between lifestyle, socioeconomic status, clinical condition, psychological distress, medical treatment and diet for the implementation of sustainable dietary patterns; b) malnutrition biomarker validation; c) draft of sustainable nutritional protocols (in connection with Spoke 1 and 4).

Task 6.2.2.

Development and application of in vitro, in vivo and in silico experimental models for the understanding of the mechanism of action in counteracting malnutrition of new sustainable bioactive molecules from different matrices (in connection with Spoke 2, 3 and 4).

Task 6.3.2.

Investigation of the preventive and therapeutic action of sustainable personalised nutrition and microbial-derived products on malnutrition-associated gut microbiome alteration and effect on specific targets with malnutrition.

Task 6.4.1.

Implementation of sustainable dietary patterns as nutritional treatment for target specific groups with malnutrition. The task includes the prototyping of foods, supplements, ingredients and nutraceuticals aimed at restoring resilience in specific targets with malnutrition (in connection with Spoke 4). In addition, it is implemented a friendly end user personalised web responsive application for remote promoting and monitoring of sustainable dietary patterns target specific.

Project deliverables

D6.1.1.1.

Systematic evaluation of existing data on nutritional status and critical issues for target specific groups with malnutrition (M8)

D6.1.1.2.

Identification and mapping of specific target groups with malnutrition (M24)

D6.1.1.3.

Creation of a biobank for biological samples in connection with Spoke 5 (M36)

D6.1.2.1.

New biomarkers of malnutrition specific for diseases and age and related to diet (M24)

D6.1.2.2.

Identification of biochemical pathways interconnected with biomarkers of malnutrition and immunological responses (M36)

D6.2.1.1.

Report on lifestyle, socioeconomic status, clinical condition, psychological distress, medical treatment, diet, cultural and environmental determinants of malnutrition in target specific populations (M24)

D6.2.1.2.

Evaluation and harmonisation of existing nutritional protocol, dietary guidelines for specific target groups with malnutrition (M10)

D6.2.1.3.

Validated biomarkers and reference ranges for specific target groups with malnutrition (M36)

D6.2.1.4.

Development of new, sustainable, easy to use diagnostic tools for early malnutrition assessment in specific target groups (M36)

D6.2.1.5.

New sustainable nutrition protocols for specific target groups with malnutrition (M20)

D6.2.2.1.

Systematic reviews of sustainable bioactive molecules, and recognized effects on malnutrition (M6)

D6.3.2.1.

Profiling of gut bacterial constituents with potential applications as postbiotics aimed at restoring immune system and metabolic functions in vulnerable subjects with malnutrition (M36)

D6.4.1.1.

Development and validation of new sustainable nutritional protocols for specific target groups with malnutrition (M36)

D6.4.1.2.

New prototypes of functional foods, food supplements, ingredients and nutraceuticals for malnutrition and malnutrition related diseases (n=5) (M36)

D6.4.1.3.

Web application for sustainable personalised nutritional protocols and cognitive behavioural support in specific target groups with malnutrition (M36)

State of the art

Celiac Disease (CeD) is one of the most common autoimmune diseases in Caucasian individuals. It develops in a subset of genetically susceptible individuals carrying the HLA-DQ2 and/or -DQ8 alleles upon the ingestion of dietary gluten and it is characterized by high levels of anti-tissue transglutaminase antibodies and a small intestinal enteropathy, often leading to malnutrition. Although 40% of the general population carries the predisposing alleles, only 1% develops CeD, suggesting a role for additional environmental triggers. Viral infections or dietary habits resulting in metabolic overload could be implicated.

Operation plan

Aim is to investigate nutritional status, dietary habits and gut microbiome of one of the largest European cohorts of pediatric patients at different stages of CeD compared to age and sex-matched controls. It will be included patients with untreated (active CeD, ACD, N=100) as well as treated CeD on a gluten-free diet (GFD, N=100) and Potential CeD (PCD, N=400). The latter group includes individuals with CeD-specific autoimmunity but no intestinal tissue damage, who are at higher risk to develop ACD overtime. As control groups it will be included healthy (HC, N=100) and disease controls (DC) including other autoimmune diseases (i.e. T1D, rheumatological diseases, etc.). A cross sectional study will be carried out to compare the groups and have a glimpse of the differences in the nutritional status associated with different stages of CeD in comparison with healthy subjects and children affected by other autoimmune conditions. In parallel it will be performed a longitudinal prospective study among PCD patients to correlate changes in dietary habits, microbiota, and viral infections with later onset of overt-CeD (ACD). Lastly, it will be dissected the role of probiotics and postbiotics in mitigating gluten-induced intestinal inflammation leading to autoimmune responses.

Expected results

To delineate immunological and molecular changes associated with the evolution to villous atrophy, factors that could favor early disease onset (i.e. viruses), biomarkers predictive of CeD progression to overt tissue damage. Those could help stratifying PCD, and deciding whom to leave on a gluten containing diet. This will help define secondary preventive strategies to avoid progression from PCD to overt-CeD.

Moreover, it is expected to identify the molecular pathways associated with gliadin-induced inflammation in healthy individuals and dissect the relative contribution of gluten and other environmental triggers in the context of CeD. It will be tested the protective role of pro and post biotics in the context of gliadin induced and CeD- associated intestinal inflammatory responses.