Research

The BAPO trial showed that oral butyrate supplementation is effective in treating pediatric obesity, significantly reducing BMI z-score (≥ 0.25 SD) and improving waist circumference, insulin resistance, and inflammatory markers compared to placebo. [https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2799197]

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. This study aims to evaluate the sensitivity and specificity of a standardized atopy patch test 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 study evaluates the preventive effect of the Mediterranean Diet during pregnancy on offspring allergy risk. In this multi-center randomized controlled trial, healthy pregnant women at risk of having an atopic baby are allocated to either a nutritional counseling group promoting the Mediterranean Diet or a standard care control group. The study aims to evaluate the occurrence of allergic disorders in the first 24 months of life, while also assessing secondary outcomes including maternal-infant gut microbiome features, breast milk composition, epigenetic modulation, and offspring metabolic pathways. [https://clinicaltrials.gov/study/NCT05119868?cond=premedi&term=berni%20canani&viewType=Card&rank=1]

The trial showed that promoting the Mediterranean diet during pregnancy is an effective strategy to prevent pediatric overweight and obesity, significantly reducing its incidence in the offspring at 24 months. This protective effect was linked to positive epigenetic modifications, specifically a higher methylation rate of the leptin gene in cord blood. [https://www.nature.com/articles/s41366-024-01626-z]

The EPIFA study provided crucial epidemiological data on childhood food allergy (FA) by screening a massive cohort of 105,151 pediatric subjects (aged 0–14 years) over a 12-year period (2009–2021). The results revealed an alarming and progressive surge in FA, with a 34% relative increase in incidence and a 113.6% spike in overall prevalence by the end of the study. This upward trend was even more dramatic in infants and toddlers aged 0–3 years, where prevalence skyrocketed by 120.8%. Identifying cow’s milk, hen’s egg, and nuts as the most frequent triggers, the EPIFA study delivered critical, large-scale evidence that underscores the urgent need for new public health and preventive strategies. [https://www.sciencedirect.com/science/article/pii/S2772829324000420?via%3Dihub]

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]

This observational study found that children with autism spectrum disorder (ASD) have a significantly increased prevalence of adverse food reactions, food allergies, and obesity compared to non-autistic healthy controls. Additionally, prominent food selectivity and low adherence to a Mediterranean diet were observed in the ASD group. These findings highlight that proactive, multidisciplinary nutritional strategies are essential to optimize health outcomes in children with ASD. [https://link.springer.com/article/10.1186/s13052-024-01794-8]

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]

This prospective cohort study investigated factors influencing the natural history of non-IgE-mediated gastrointestinal food allergies (non-IgE-GIFA) in 123 children. The data showed that early diagnosis is crucial, as diagnostic delays and baseline multiple allergies increase the risk of the allergic march. Ultimately, the study highlighted how specific risk factors influence both the development of multiple allergies and 24-month tolerance outcomes. [https://bmjpaedsopen.bmj.com/content/9/1/e003203]

This prospective study analyzed the gut microbiome of 90 allergic children and 30 healthy controls, revealing a pro-inflammatory dysbiosis driven by Ruminococcus gnavus enrichment and a depletion of beneficial taxa. By proving that baseline microbial signatures can predict whether a child will acquire immune tolerance, these findings paved the way for novel preventive and therapeutic strategies in pediatric allergic diseases. [https://www.nature.com/articles/s41467-021-26266-z]

The ProPAD study was a randomized, double-blind, controlled trial investigating the therapeutic effects of the probiotic Lacticaseibacillus rhamnosus GG (LGG) in 100 children with atopic dermatitis (AD). Supplementation with LGG for 12 weeks significantly reduced AD severity, decreased the need for rescue medications, and improved patients’ quality of life. These clinical benefits paralleled a beneficial modulation of both gut and skin microbiomes, suggesting LGG as a valuable adjunctive therapy for pediatric AD. [https://onlinelibrary.wiley.com/doi/10.1111/pai.13836]

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.

The SDACMA trial showed that a step-down from amino acid formula to EHCF+LGG is well tolerated (0.98, 95% CI 0.91-0.99) and effective in IgE-mediated CMA children, significantly increasing the 12-month immune tolerance rate compared to continuous AAF (0.48, n/N=14/29 vs 0.03, n/N=1/30; NNT=2) while ensuring normal body growth. [https://onlinelibrary.wiley.com/doi/10.1111/all.15750]

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]

Unhealthy lifestyle habits during the childhood could negatively impact the health status during infancy and the later stages of life. The School represents the major Institution to implement actions aim at promoting healthy lifestyles habits. The Joint School-Health Project of the Neapolitan Child aimed at assessing the impact of a health education programme to improve lifestyle habits during the childhood. To evaluate the effects of this educational programme, the dietary habits, the sleep hours, the hours spent in sedentary behaviors (tv, smartphone) and the hours of physical activity will be evaluate at the baseline and at the end of the educational programme. [ClinicalTrial.gov link Study Details | NCT05901220 | Joint School-Health Project of the Neapolitan Child | ClinicalTrials.gov]

This 36-month prospective cohort study involving 365 infants compared the impact of five different formulas on the natural history of IgE-mediated cow’s milk allergy (CMA). The results demonstrate that first-line dietary management with an extensively hydrolyzed casein formula containing the probiotic Lacticaseibacillus rhamnosus GG (EHCF+LGG) significantly reduces the incidence of future atopic manifestations, such as eczema and asthma, and accelerates the rate of immune tolerance acquisition compared to rice, soy, amino acid-based, or hydrolyzed whey formulas. [https://www.sciencedirect.com/science/article/pii/S0022347621000937?via%3Dihub]

The incidence of Eosinophilic esophagitis (EoE) is rising sharply in Western countries, highlighting the potential impact of dietary factors such as ultra-processed foods (UPFs). This study investigates the role of UPF-derived advanced glycation end-products (AGEs) in EoE pathogenesis. Dietary AGEs accumulate in the body and interact with their cell-surface receptor (RAGE), triggering oxidative stress, tissue damage, and mast cell activation. By inducing a chronic Th2-biased inflammatory state, these industrial food compounds emerge as key environmental triggers for EoE. [ https://clinicaltrials.gov/study/NCT06093204]

The drastic increase in ultra-processed food (UPF) consumption in industrialized countries has raised concerns due to high levels of advanced glycation end-products (AGEs), which drive oxidative stress and inflammation linked to obesity and allergies. While a maternal diet rich in AGEs during pregnancy and lactation is suspected to negatively affect infant health, data on UPF derivatives in human milk remain unavailable. The UFIM (Ultraprocessed Foods In Breast Milk) study aims to evaluate and quantify the presence of these dietary compounds in breast milk. [ClinicalTrial.gov link Study Details | NCT05889520 | The UFIM (Ultraprocessed Foods In Breast Milk) Project | ClinicalTrials.gov]

The NAPFA score is an innovative, easy-to-use clinical tool developed to facilitate and standardize the diagnostic approach for pediatric food allergies. Validated in a prospective cohort of 627 children, the score combines clinical data and allergy screening to accurately predict the probability of food allergy. By streamlining the diagnostic workflow, this tool holds the potential to significantly reduce unnecessary medical testing and eliminate diagnostic delays in clinical practice. [https://pmc.ncbi.nlm.nih.gov/articles/PMC11956138/]

This study investigated the pathophysiological mechanisms of pediatric obesity, focusing on the role of ultra-processed foods (UPFs) and advanced glycation end-products (AGEs). Results from 53 pediatric patients with obesity and 100 healthy controls revealed that patients had significantly higher UPFs and AGEs intake, along with highers skin AGEs accumulation, and altered mitochondrial metabolism. These cellular alterations were replicated in vitro, by exposing cells from healthy controls with AGEs, providing strong mechanistic validation for dietary interventions targeting UPFs and ther detrimental compounds AGEs [https://pmc.ncbi.nlm.nih.gov/articles/PMC10400566/]

‘Tackling Malnutrition’ is focused on developing nutritional strategies targeting the most vulnerable categories of the national population (i.e., families in the condition of financial hardship, people affected by pathologies, or older people), thus ensuring adequate nutrition and limiting the onset of malnutrition situations that would end up reducing resilience and aggravating conditions of frailty. We are a partnership for the Sustainable Development of Food and Nutrition, funded under the Italian National Recovery and Resilience Plan (NRRP).

Breast milk is considered the gold standard for infant nutrition due to its ability to provide adequate nutrition and a high amount of protective factors for the baby’s health. According to the guidelines of the World Health Organization (WHO), exclusive feeding with breast milk should be conducted until the end of 6 months of life and should be continued in the following months with the simultaneous introduction of complementary foods. Several scientific evidence demonstrates that breastfeeding is associated with positive health outcomes, both during infancy and in later life. Given the protective role of breast milk for health, studying its content is of fundamental importance to have an integrated vision of the biological effects of its components on the health of the child, and of the factors that are able to modulate its composition. The “Building a Deeper Knowledge on Breast Milk Composition” (BuKoBc) project was designed to study the content of human milk in its entirety and at different times during the feeding and during the day, also in relation to environmental factors capable of modulating its composition. The results of this study may provide data on optimal reference ranges for nutrient intake in breastfed infants and may provide guidance in defining optimal nutrient intake for infants who cannot be breastfed. Furthermore, the in-depth study of the environmental factors capable of influencing the composition of breast milk will allow the development of nutritional intervention strategies for the breastfeeding mother in order to positively modulate the composition of her milk. [https://clinicaltrials.gov/study/NCT06152835]

The latest data from the World Health Organization (WHO) shows that malnutrition in all of its forms affects over 2.5 billion people globally. This condition is constantly increasing and affects the entire population, from childhood to the elderly. Malnutrition in all its forms negatively impacts the quality of life of patients affected and increases the risk of morbidity and mortality, as well as healthcare costs. Considering the complexity and multifactorial nature of malnutrition, the integration of multiomics data obtained from analyses with high-throughput technologies such as epigenomics, metagenomics, metabolomics, could benefit the prediction and evaluation of prognosis and/or response to specific treatments; this could pave the way for personalized precision medicine interventions for patients suffering from malnutrition. The “Science Against Malnutrition Project” (SAM) aims at characterize malnutrition through the identification of specific biomarkers of the condition with the goal of developing innovative prevention and treatment programs. [https://clinicaltrials.gov/study/NCT06152848]

Pediatric Food allergy (FA) is an increasing health problem worldwide with significant socioeconomic costs for the families and health care system. Genetic and epigenetic mechanisms involved in FA occurrence are not fully understood, which hampers the development of effective diagnostic, preventive and therapeutic strategies. Several genes could play a role in pediatric FA. Gene expression can be modulated by different epigenetic mechanisms regulated by several environmental factors. These epigenetic mechanisms could have a role on FA occurrence and disease course. We will focus on genetic and epigenetic mechanisms involved in FA with the aim of identifying innovative biomarkers and targets for limiting the disease burden and reducing the socio-economic costa for the families and the health care system.

Nickel, the main responsible for allergic contact dermatitis worldwide, is known to be also causative of “Systemic Nickel Sulfate Allergy Syndrome (SNAS)” characterized by cutaneous symptoms but also by respiratory, neurological, and/or gastrointestinal symptoms due to immune-dysregulation caused by the ingestion of nickel containing foods. Other food allergies (FA), in particular Lipid Transfer Proteins (LTPs) allergies are emerging as one of the most common FA in Mediterranean countries, including in pediatric populations. The symptoms of LTP allergies are highly variable being completely asymptomatic in many sensitized patients or experiencing contact urticaria, oral allergy syndrome and/or gastrointestinal symptoms including vomiting, and abdominal pain up to anaphylaxis.
Gastroesophageal reflux (GERD), dyspepsia, abdominal pain, and bowel alterations not secondary to organic disease, are generally classified as functional gastrointestinal disorders but, according to the literature, 40% of adult patients classified as functional gastrointestinal symptoms show sensitization to nickel; however, data regarding the pediatric population are lacking. The aim of this study is to assess the prevalence of sensitization to nickel and LTPs in patients presenting with symptoms of functional dyspepsia and irritable bowel syndrome. Nickel, the main responsible for allergic contact dermatitis worldwide, is known to be also causative of “Systemic Nickel Sulfate Allergy Syndrome (SNAS)” characterized by cutaneous symptoms but also by respiratory, neurological, and/or gastrointestinal symptoms due to immune-dysregulation caused by the ingestion of nickel containing foods. Other food allergies (FA), in particular Lipid Transfer Proteins (LTPs) allergies are emerging as one of the most common FA in Mediterranean countries, including in pediatric populations. The symptoms of LTP allergies are highly variable being completely asymptomatic in many sensitized patients or experiencing contact urticaria, oral allergy syndrome and/or gastrointestinal symptoms including vomiting, and abdominal pain up to anaphylaxis.
Gastroesophageal reflux (GERD), dyspepsia, abdominal pain, and bowel alterations not secondary to organic disease, are generally classified as functional gastrointestinal disorders but, according to the literature, 40% of adult patients classified as functional gastrointestinal symptoms show sensitization to nickel; however, data regarding the pediatric population are lacking. The aim of this study is to assess the prevalence of sensitization to nickel and LTPs in patients presenting with symptoms of functional dyspepsia and irritable bowel syndrome. 

Atopic dermatitis (AD) is a chronic, multifactorial inflammatory skin disease characterized by eczematous skin and pruritus, and characterized by a disruption of the skin barrier with alterations of the gut and skin microbiome (SM). Disturbance of the SM in skin diseases leads to a reduction in microorganisms that produce butyrate, a short-chain fatty acid (SCFA), which is able to reduce skin permeability by improving barrier properties and suppressing inflammatory skin responses. Furthermore, a reduction in butyrate in patients with AD has been also demonstrated at the intestinal level. Conventional therapy for AD consists of the elimination of exacerbating factors, the application of emollients and in flare-ups, or in moderate/severe forms, the application of topical steroids or topical calcineurin inhibitors. Both topical corticosteroids and calcineurin inhibitors can lead to local and systemic side effects, including skin atrophy, purpura, striae, telangiectasia, hypopigmentation, acne, up to suppression of the hypothalamic-pituitary-adrenal axis and growth retardation. Furthermore, especially for topical calcineurin inhibitors, their high cost limits their use. The possibility of using emollients containing substances physiologically present in the skin, such as butyrate, could represent a safe treatment strategy, capable of reducing exacerbations and therefore the evolution towards moderate-severe forms of AD. On the basis of these premises, the BuPad study was born, which aims to evaluate the therapeutic efficacy of the cutaneous application of the postbiotic sodium butyrate in a cosmetic formulation in children affected by AD. [https://clinicaltrials.gov/study/NCT07016087?cond=atopic%20dermatitis&term=berni%20canani&viewType=Card&rank=2]

Water sports, particularly water polo and synchronized swimming, require specific nutritional strategies to optimize performance and recovery. Proper nutrition timing and adequate intake of nutrients are crucial for maintaining energy levels, supporting muscle recovery, and enhancing overall athletic performance. NutriWater is a Pilot, monocentric, prospective study whose main objective is to evaluate the impact of nutritional counseling on nutritional status and athletic performance in water polo and synchronized swimming athletes.

The purpose of the study is to determine whether a new extensive liquid casein hydrolysate is hypoallergenic in infants and young children with documented Immunoglobulin E (IgE)-mediated Cow Milk Protein Allergy (CMPA).

The purpose of the study is to determine whether a new hydrolyzed rice protein-based formula is hypoallergenic in infants and young children with documented Immunoglobulin E (IgE)-mediated Cow Milk Protein Allergy (CMPA).

The main purpose of this study is to demonstrate that the growth of infants fed with the Test Formula is non-inferior those fed with the Control Formula. The study will also evaluate the gastrointestinal tolerance, quality of life and acceptability of the new rice protein-based formula in infants with cow’s milk protein allergy (CMPA).