Research

The research at the ImmunoNutritionLab is focused on modern nutritional interventions with a pivotal role in improving the health status of both current and future generations.

A Translational Approach

The ImmunonutritionLab is at the forefront of biomedical innovation thanks not only to its basic research activity, but also to the development and testing of new protocols.

The ImmunonutritionLab integrates basic and clinical research through a translational approach: laboratory findings are quickly translating into clinical therapies and procedures (bench to bedside).

Its commitment to the improvement of clinical practice is proven by numerous ongoing clinical trials and by many new study proposals submitted from Industries. These activities have steadily grown during the years thanks to the support provided by the patients’ fidelity and Industries estimation.

Clinical
Studies

Clinical Studies

The BAPO trial is a randomized, quadruple-blind, placebo controlled, clinical trial on obese pediatric patients of both sex, aged 7-16 years. Subjects are randomly assigned to one of the two 6-month intervention groups: standard care for pediatric obesity + butyrate or placebo. The primary outcome is a BMI z-score reduction ≥ 0.25, the secondary outcomes are the effects on glucose and lipid profile, waist circumference, mir221- expression, serum hormones/adipokines, eating behaviors and gut microbiota composition. [ClinicalTrial.gov link]
Non-IgE mediated food allergies are characterized by gastrointestinal symptoms (diarrhea, vomiting, bloody stool, persistent distress/colic, regurgitation and constipation) and Cow’s Milk is the most frequent involved food. There are no validated tests for the diagnosis of non-IgE Cow’s Milk allergy (CMA), apart from the oral food challenge. The V1605-201/APTITUDE study aims to evaluate the sensitivity and specificity of a standardized Atopy patch test DBV1605 in the diagnosis of non-IgE mediated CMA. [ClinicalTrial.gov link]
Long chain polyunsaturated fatty acids (PUFAs) play a role in allergic diseases. Observations link n-3 PUFA docosahexaenoic acid (DHA) to allergy prevention. Preliminary results reported association between food allergy and dysbalanced PUFAs metabolism. The study aims to explore the influence of crucial enzymatic activities in PUFAs metabolism, delta-5, (FADS1) and delta-6 (FADS2) desaturase, gene polymorphisms on n-6 and n-3 serum levels in children with IgE-mediated cow milk allergy (CMA).
The PREMEDI (MEditerranean DIet during PREgnancy) study is a primary prevention randomized clinical trial aiming to evaluate the effects of Mediterranean diet (MD) during pregnancy on epigenetic mechanisms that regulate the expression of the genes involved in the pathogenesis of obesity and allergy in the offspring. It also aims to evaluate the effects of MD on structure and function of maternal and neonatal gut microbiota, maternal weight gain and complications, fetal complications, neonatal outcomes, child growth, and allergic manifestations. [ClinicalTrial.gov link]
Several evidences in the literature suggest a change in the epidemiological scenario of food allergies (FA) in the last decade, with an increase in the prevalence, persistence and severity of clinical manifestations. Recent data on the epidemiology of FA in the Italian pediatric age in the last decade are currently scarce. The EPIFA study aims to update the epidemiological data to facilitate the definition of prevention and intervention strategies for the correct management of these conditions.
MATOMS is an observational, transversal, comparative study to evaluate comparatively the metagenomics and metabolomics characteristics of gut microbiome of children/adolescents of both sex, aged between 10-16 years with obesity, obesity complicated by metabolic syndrome and healthy controls matched for age and sex. [ClinicalTrial.gov link]
Autism Spectrum Disorders (ASD) is a severe neurological condition characterized by severe stereotypical behaviors and deficits in social interaction. Preliminary data suggest that particular elimination diets and/or modifications of the intestinal microbiota can determine a positive effect on the symptoms of ASD. Observational study in which we evaluate eating habits, adverse food reactions and the effects of the elimination diet on ASD symptoms and we characterize the composition and function (production of short-chain fatty acids, SCFA) of the intestinal microbiota in children with ASD and in healthy children. [ClinicalTrial.gov link]

Autistic Spectrum Disorder (ASD) is a complex group of behavioral disorders characterized by defects in social interaction and communication associated with repetitive behaviors. Alterations in nutritional status, eating habits and adverse reactions to food appear to be common in children with ASD. Randomized prospective study whose main objective is the evaluation of the impact of a nutritional intervention on the reduction of food selectivity and as secondary the evaluation of the improvement of eating habits, adherence to the Mediterranean Diet, auxological parameters and quality of life of parents. [ClinicalTrial.gov link]

Non-IgE mediated gastrointestinal food allergy is an evolving web of clinical conditions characterized by subacute and/or chronic symptoms and include food protein-induced: enterocolitis syndrome (FPIES), enteropathy (FPE), allergic proctocolitis (FPIAP), and motility disorders (FPIMD). Despite the epidemiological relevance, pathogenesis, best diagnostic and therapeutic approach, and natural history of these disorders are still poorly characterized. The NIGEFA project is focused on the study of the pathogenesis and natural history of non-IgE mediated gastrointestinal food allergy in the pediatric age. [ClinicalTrial.gov link]
The MATFA study is designed to explore the influence of gut microbiome in pediatric allergy with “Shotgun Metagenomics” approach. We comparatively aimed to define metagenomics and metabolomics features in children affected by food allergy or respiratory allergies and in healthy controls for the development of new strategies for the prevention and treatment of allergy. [ClinicalTrial.gov link]

Atopic dermatitis (AD) is a multifactorial, chronic inflammatory skin disorder that results in areas of dry, itchy skin. AD is typified by defective skin barrier function with activation of abnormal immunological and inflammatory pathways upon exposure to ubiquitous environmental allergens. Specific probiotics have been shown to normalize intestinal permeability, to counteract intestinal immune dysfunction and to normalize gut dysbiosis. The aim of this randomized, double-blind, placebo-controlled study is to evaluate the efficacy of the most studied probiotic in the pediatric allergy field – L.rhamnosus GG – in children affected by atopic dermatitis. [ClinicalTrial.gov link]

Epigenetic mechanisms could drive the disease course of cow’s milk allergy (CMA) and formula choice could modulate these mechanisms. Our group demonstrated a significant difference in DNA methylation of T helper (Th)1/Th2 cytokine and of FoxP3 genes, concomitantly an up-regulation of microRNAs involved in Th1/Treg response, in children who acquired immune tolerance after treatment with extensively hydrolyzed casein formula containing the probiotic L.rhamnosus GG compared to soy formula. EPICMA II aims to evaluate the effect of other different formulas available for the dietary treatment of CMA on epigenetic mechanisms in CMA children. [ClinicalTrial.gov link]

The treatment of FA is based on a rigorous elimination diet and on the correct management of acute allergic reactions. The daily management of a correct elimination diet and a possible allergic reaction, entail a significant burden and high levels of anxiety and stress in mothers of children with FA, resulting in an impact on Quality of Life (QoL). The objectives of the study are to validate the Italian version of two specific questionnaires for food allergies and to explore the potential differences in the QoL of mothers of children with FA followed by a multidisciplinary team. [ClinicalTrial.gov link]

Atopic dermatitis (AD) is a multifactorial, chronic inflammatory skin disorder that results in areas of dry, itchy skin. AD is typified by defective skin barrier function with activation of abnormal immunological and inflammatory pathways upon exposure to ubiquitous environmental allergens. Specific probiotics have been shown to normalize intestinal permeability, to counteract intestinal immune dysfunction and to normalize gut dysbiosis. The aim of this randomized, double-blind, placebo-controlled study is to evaluate the efficacy of the most studied probiotic in the pediatric allergy field – L.rhamnosus GG – in children affected by atopic dermatitis. [ClinicalTrial.gov link]

The PSC-DS DG BABY 18 is a randomized, double-blind, placebo controlled clinical trial to evaluate the efficacy and safety of L. casei DG® (L. paracasei CNCM I-1572) in the treatment of infantile colic. The secondary outcomes are the reduction of the average daily crying time, the persistence of infantile colic, the reduction in the number of regurgitation episodes, evaluation of the fecal consistency and frequency, evaluation of the number of infectious.

Preclinical
studies

Preclinical studies

Current hypotheses and models of food allergy (FA) do not adequately explain the dramatic increase observed in the last years. It has been hypothesized that advanced glycation endproducts (AGEs), present at high level in junk food (sugars, roasted/barbecued meat), could be involved in FA pathogenesis. The aim of our project is to evaluate the subcutaneous AGEs levels and the correlation with dietary habit in children with challenge-proven FA, children with respiratory allergy and age and sex-matched healthy controls. Pathogenetic mechanisms elicited by AGEs were also investigated in a cellular model of human enterocytes and in peripheral blood mononuclear cells from children at risk for atopy. [ClinicalTrial.gov link]

Rotavirus (RV) is the leading cause of severe childhood acute gastroenteritis (AGE). Each year, RV is responsible for about 25 million clinic visits, two million hospital admissions, and 180 000–450 000 deaths in children under 5 years of age globally. Clinical evidences suggest the potential of the postbiotic approach based on cow milk fermentation with the probiotic L. paracasei CBAL74 (FM-CBAL74) in preventing pediatric infectious diseases. The aim of this study is to evaluate the preventive action elicited by FM-CBAL74 against Rotavirus-induced AGE in a well-established in vitro model of human enterocytes. [ClinicalTrial.gov link]

Several formulas are available for the dietary treatment of cow’s milk allergy (CMA). Formulas available for CMA treatment differ mainly regarding the protein fraction features, such as source (cow’s milk, soy, or rice), degree and procedure of hydrolysis. Clinical data suggest potential different effect on immune tolerance elicited by these formulas. The aim of this study is to comparatively evaluate the tolerogenic effect elicited by the protein fraction of different formulas available for the dietary treatment of CMA. [ClinicalTrial.gov link]