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Background Amino acid-based formula (AAF) is a relevant dietary strategy for paediatric patients affected by cow’s milk allergy (CMA). The present study was designed to evaluate the hypoallergenicity of a new AAF in children with immunoglobulin (Ig)E-mediated CMA. Methods According to the criteria provided by the American Academy of Pediatrics Subcommittee on Nutrition and Allergic Diseases, we designed a prospective trial in CMA children (aged 1–36 months) aimed to demonstrate the hypoallergenicity of the new AAF in 90% of subjects with 95% confidence during the double-blind, placebo-controlled challenge (DBPCFC). A skin prick test (SPT) with the new AAF was also performed. Results Twenty-nine children [all Caucasian, 55.2% male, mean age (±SD) 16.9 ± 5.7 months] were enrolled. The SPT and the DBPCFC with the new AAF were negative in all study subjects. Conclusions The study results support the hypoallergenicity of the new AAF. This formula could be considered an additional dietary option for non-breastfed children affected by CMA. Trial registration The trial was registered in the ClinicalTrials.gov Protocol Registration System (ID number: NCT03909113).

Background Food allergy (FA) is a growing health problem worldwide. Effective strategies are advocated to limit the disease burden. Human milk (HM) could be considered as a protective factor against FA, but its mechanisms remain unclear. Butyrate is a gut microbiota‐derived metabolite able to exert several immunomodulatory functions. We aimed to define the butyrate concentration in HM, and to see whether the butyrate concentration detected in HM is able to modulate the mechanisms of immune tolerance. Methods HM butyrate concentration from 109 healthy women was assessed by GS‐MS. The effect of HM butyrate on tolerogenic mechanisms was assessed in in vivo and in vitro models. Results The median butyrate concentration in mature HM was 0.75 mM. This butyrate concentration was responsible for the maximum modulatory effects observed in all experimental models evaluated in this study. Data from mouse model show that in basal condition, butyrate up‐regulated the expression of several biomarkers of gut barrier integrity, and of tolerogenic cytokines. Pretreatment with butyrate significantly reduced allergic response in three animal models of FA, with a stimulation of tolerogenic cytokines, inhibition of Th2 cytokines production and a modulation of oxidative stress. Data from human cell models show that butyrate stimulated human beta defensin‐3, mucus components and tight junctions expression in human enterocytes, and IL‐10, IFN‐γ and FoxP3 expression through epigenetic mechanisms in PBMCs from FA children. Furthermore, it promoted the precursors of M2 macrophages, DCs and regulatory T cells. Conclusion The study's findings suggest the importance of butyrate as a pivotal HM compound able to protect against FA., Human milk contains a significant level of the short‐chain fatty acid butyrate. At concentration detectable in human milk, butyrate effectively modulates several tolerogenic mechanisms involved in the protection against food allergy. The protective role of human milk against food allergy could be related, at least in part, to the presence of an effective concentration of butyrate

Summary Background The pathogenesis of infant colic is poorly defined. Gut microbiota seems to be involved, supporting the potential therapeutic role of probiotics. Aims To assess the rate of infants with a reduction of ≥50% of mean daily crying duration after 28 days of intervention with the probiotic Bifidobacterium animalis subsp. lactis BB‐12® (BB‐12). Secondary outcomes were daily number of crying episodes, sleeping time, number of bowel movements and stool consistency. Methods Randomized controlled trial (RCT) on otherwise healthy exclusively breastfed infants with infant colic randomly allocated to receive BB‐12 (1 × 109 CFU/day) or placebo for 28 days. Gut microbiota structure and butyrate, beta‐defensin‐2 (HBD‐2), cathelicidin (LL‐37), secretory IgA (sIgA) and faecal calprotectin levels were assessed. Results Eighty infants were randomised, 40/group. The rate of infants with reduction of ≥50% of mean daily crying duration was higher in infants treated with BB‐12, starting from the end of 2nd week. No infant relapsed when treatment was stopped. The mean number of crying episodes decreased in both groups, but with a higher effect in BB‐12 group (−4.7 ± 3.4 vs −2.3 ± 2.2, P

ImportanceThe pediatric obesity disease burden imposes the necessity of new effective strategies.ObjectiveTo determine whether oral butyrate supplementation as an adjunct to standard care is effective in the treatment of pediatric obesity.Design, Setting, and ParticipantsA randomized, quadruple-blind, placebo-controlled trial was performed from November 1, 2020, to December 31, 2021, at the Tertiary Center for Pediatric Nutrition, Department of Translational Medical Science, University of Naples Federico II, Naples, Italy. Participants included children aged 5 to 17 years with body mass index (BMI) greater than the 95th percentile.InterventionsStandard care for pediatric obesity supplemented with oral sodium butyrate, 20 mg/kg body weight per day, or placebo for 6 months was administered.Main Outcomes and MeasuresThe main outcome was the decrease of at least 0.25 BMI SD scores at 6 months. The secondary outcomes were changes in waist circumference; fasting glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, ghrelin, microRNA-221, and interleukin-6 levels; homeostatic model assessment of insulin resistance (HOMA-IR); dietary and lifestyle habits; and gut microbiome structure. Intention-to-treat analysis was conducted.ResultsFifty-four children with obesity (31 girls [57%], mean [SD] age, 11 [2.91] years) were randomized into the butyrate and placebo groups; 4 were lost to follow-up after receiving the intervention in the butyrate group and 2 in the placebo group. At intention-to-treat analysis (n = 54), children treated with butyrate had a higher rate of BMI decrease greater than or equal to 0.25 SD scores at 6 months (96% vs 56%, absolute benefit increase, 40%; 95% CI, 21% to 61%; P P P = .03); HOMA-IR, −1.14 (95% CI, −2.13 to −0.15; P = .02); ghrelin level, −47.89 μg/mL (95% CI, −91.80 to −3.98 μg/mL; P P P Conclusions and RelevanceOral butyrate supplementation may be effective in the treatment of pediatric obesity.Trial RegistrationClinicalTrials.gov Identifier: NCT04620057

Lactose intolerance is a common gastrointestinal condition caused by the inability to digest and absorb dietary lactose. Primary lactose intolerance is the most common type of lactose intolerance. It is one of the most common forms of food intolerance and occurs when lactase activity is reduced in the brush border of the small bowel mucosa. People may be lactose intolerant to varying degrees, depending on the severity of these symptoms. When lactose is not digested, it is fermented by gut microbiota, leading to abdominal pain, bloating, flatulence, and diarrhea with a considerable intraindividual and interindividual variability in the severity of clinical manifestations. These gastrointestinal symptoms are similar to cow's milk allergy and could be wrongly labeled as symptoms of “milk allergy.” There are important differences between lactose intolerance and cow's milk allergy. Therefore, a better knowledge of these differences could limit misunderstandings in the diagnostic approach and in the management of these conditions. [ Pediatr Ann . 2021;50(4):e178–e185.]

The fatty acid (FA) composition of human milk (HM) from N = 9 Italian healthy donors following a free diet exhibited FA-dependent ranges of variability, as assessed by GC-FID. The possible short-term changes in the FA profile were monitored in the milk of lactating mothers (three) collected at five time points over a 6 h period, following an oral load (200 mL) of bovine milk. An array of techniques was exploited, including UHPLC-ESI-MS/MS of intact lipids and MALDI-TOF MS before and after chemical hydrogenation or bromination, in addition to MALDI-TOF MS analysis of FA after saponification, to monitor short-chain and odd-chain FA in HM as markers of bovine milk fat. A single administration of bovine milk did not appreciably modify the lipid pattern, suggesting that the maternal diet could induce not detectable short-term changes on the lipid composition of HM. Diet-induced increase of butyric acid was also excluded by 13C-NMR. The functions that HM FA exert in infant physiology appear finely regulated through maternal metabolism.

The dramatic increase in food allergy prevalence and severity globally is demanding effective strategies. Food allergy derives from a defect in immune tolerance mechanisms. Immune tolerance is modulated by gut microbiota composition and function, and gut microbiota dysbiosis has been associated with the development of food allergy. Selected probiotic strains could act on immune tolerance mechanisms. The mechanisms are multiple and still not completely defined. Increasing evidence is providing useful information on the choice of optimal bacterial species/strains, dosage, and timing for intervention. The increased knowledge on the crucial role played by gut microbiota-derived metabolites, such as butyrate, is also opening the way to a post-biotic approach in the stimulation of immune tolerance.

prevalence has dramatically increased in the last two decades. Among dietary factors, it has been hypothesized that advanced glycation endproducts(AGEs), present at high level in junk food, could be involved in FA pathogenesis. AGEs are a heterogeneous group of compounds deriving from sugars(sweets and beverages), autoclaved/processed foods, microwaved foods, more roasted/barbecued meat. To evaluate the AGEs levels in FA children compared with healthy controls and subjects with respiratory allergy. Methods: We evaluated paediatric patients with challenge-proven FA, children with respiratory allergy(RA) and age and sex-matched healthy controls. Subcutaneous AGEs levels were evaluated through the AGE reader. Food-frequency questionnaires were evaluated in all study subjects. In vitro studies were performed on human enterocytes(Caco-2 cells) stimulated with 200 mg/ml of BSA-AGE for 24and48 hours to evaluate effects on gut barrier function: mucin2(mucus production), transpithelial electrical resistance(TEER), ZO-1, occludin expression(intestinal permeability). The direct effects elicited on peripheral blood mononuclear cells (PBMCs) after the treatment with 200 mg/ml of BSA-AGE for 48hours, 4and 7days of treatment were also evaluated. RESULTS: 115 subjects were evaluated and subdivided into 3 groups: group 1 patients with FA (n=31); group 2 patients with RA (n=18), group 3 healthy controls (n=66). The consumption of food containing AGEs was higher in subjects with FA compared to RA children and healthy controls (p

Epigenetic mechanisms could drive the disease course of cow’s milk allergy (CMA) and formula choice could modulate these pathways. We compared the effect of two different dietary approaches on epigenetic mechanisms in CMA children. Randomized controlled trial on IgE-mediated CMA children receiving a 12-month treatment with extensively hydrolyzed casein formula containing the probiotic L.rhamnosus GG (EHCF + LGG) or with soy formula (SF). At the baseline, after 6 and 12 months of treatment FoxP3 methylation rate and its expression in CD4+ T cells were assessed. At same study points IL-4, IL-5, IL-10, and IFN-γ methylation rate, expression and serum concentration, miRNAs expression were also investigated. 20 children (10/group) were evaluated. Baseline demographic, clinical and epigenetic features were similar in the two study groups. At 6 and 12 months, EHCF + LGG group showed a significant increase in FoxP3 demethylation rate compared to SF group. At the same study points, EHCF + LGG group presented a higher increase in IL-4 and IL-5 and a higher reduction in IL-10 and IFN-γ DNA methylation rate compared to SF group. A different modulation of miR-155, -146a, -128 and -193a expression was observed in EHCF + LGG vs. SF. Dietary intervention could exert a different epigenetic modulation on the immune system in CMA children.

Epigenetic mechanisms could drive the disease course of cow's milk allergy (CMA) and formula choice could modulate these pathways. We compared the effect of two different dietary approaches on epigenetic mechanisms in CMA children. Randomized controlled trial on IgE-mediated CMA children receiving a 12-month treatment with extensively hydrolyzed casein formula containing the probiotic L.rhamnosus GG (EHCF + LGG) or with soy formula (SF). At the baseline, after 6 and 12 months of treatment FoxP3 methylation rate and its expression in CD4

are available for the dietary treatment of cow’s milk allergy (CMA). Safety and nutritional profile of these formulas have been well evaluated, but the potential tolerogenic activity elicited by their protein fraction is still largely undefined. We aimed to comparatively evaluate the tolerogenic effect elicited by protein fraction derived from different hypoallergenic formulas available for the dietary treatment of CMA METHODS: Four hypoallergenic formulas were compared: extensively whey formula (EHWF), extensively hydrolyzed casein formula (EHCF), hydrolyzed rice formula (RHF), amino acid based formula (AAF). Formulas were reconstituted in water according to manufacturer’s instructions, and subjected to in vitro infant gut simulated digestion using a sequential gastric and duodenal static model. Resulting protein fractions were purified using C18 reversed phase pre-packed cartridges (Sep-Pak, Waters, Milford, MA, USA),recovered in 70% acetonitrile/0.1% trifluoroacetic acid and finally vacuum-dried. Tolerogenic effects were was evaluated in peripheral blood mononuclear cells (PBMCs) from 6 patients, with challenge-proven IgE-mediated CMA (age range 1-5 yrs, all Caucasians), stimulated with different doses of digested protein fractions (from 0.25 to 250 μg/ml) or -lactoglobulin (BLG;100μg/ml) or bovine serum albumin (BSA;100μg/ml) as positive and negative control respectively. The production of Th2 (IL-4, IL-5, IL-13) and Th1 (IL-10, IFN-γ) cytokines were assessed by ELISA. Modulatory action was also evaluated on immune (IL-33) and non-immune tolerogenic factors (mucin 5AC, tight-junction proteins ZO-1 and occludin) in human enterocytes (Caco-2 cells) by ELISA and Real Time PCR, respectively. RESULTS: Th2 cytokines were unaffected by the exposure to protein fraction from all study formulas, whereas only protein fraction from EHCF was able to positively modulate IL-10, IL-33, mucin 5AC, ZO-1 and occludin expression. All protein fraction from study formulas were able to increase INF-γ expression in PBMCs. CONCLUSION: The results suggest a different regulatory action on immune and non-immune tolerogenic mechanisms elicited by protein fraction from different hypoallergenic formulas.

Fatty liver disease is a serious complication of childhood obesity. Calorie-restricted regimen (RCR) is one of the effective therapy for this condition. Aim of the study was to evaluate the effect of lycopene-rich tomato sauce with oregano and basil extracts in obese children with fatty liver on RCR. 61 obese children with fatty liver were enrolled, 52 completed the study. A randomized cross over clinical trial was performed. Participants were assigned to RCR alone or with a supplement of lycopene-rich tomato juice for 60 days, subsequently, the groups were switched to the alternative regimen for the next 60 days. Reduction in BMI, HOMA-IR, cholesterol, triglycerides, liver size, and steatosis was more profound in tomato-supplemented group. Leptin decreased in both groups whereas adiponectin raised only after tomato supplementation. RCR is associated with the impaired engagement of T-cells glycolysis and proliferation, tomato-supplementation resulted in glycolytic metabolic activation of T-cells. Tomato juice ameliorates glucose and lipid metabolism in obese children, improve oxidative and inflammatory state and modulates the mitochondrial metabolism of T-cells contributing to a maintenance of a proper immune surveillance in children, impaired by RCR. The addition of tomato to RCR could be considered a protective and preventive support to obese child.

Food allergies (FAs) are an increasing problem in Western countries, affecting up to 10% of young children. FAs are frequently associated with gastrointestinal manifestations. The role of FAs as a potential causative factor for infantile colic (IC) is still controversial. We report the most recent evidence on the pathogenesis, clinical and diagnostic aspects of FA-induced infantile colic (IC) and suggest a stepwise diagnostic approach. We selected articles on clinical and immunologic features, pathogenesis and management of FAs and IC from of 1981 to 2015. Original and review articles were identified through selective searches performed on PubMed, using the following terms: colic, infantile colic, food allergy and infantile colic, infantile colic treatment. The possible relationship between FAs and IC derives from the presence of dysmotility with visceral hypersensitivity and dysbiosis, demonstrated in both conditions, and the clinical response to dietary interventions. Unfortunately, the design of the studies, poor characterization of atopy and different dietary approaches limit the understanding of the importance of FAs in subjects with IC. The role of FAs in IC subjects without other symptoms of atopy remains controversial. However, where there is a suspicion of FAs, a short trial with an extensively hydrolyzed cow’s proteins formula or, if breast fed, with maternal elimination diet may be considered a reasonable option.

The gut microbiota plays a pivotal role in immune system development and function. Modification in the gut microbiota composition (dysbiosis) early in life is a critical factor affecting the development of food allergy. Many environmental factors including caesarean delivery, lack of breast milk, drugs, antiseptic agents, and a low-fiber/high-fat diet can induce gut microbiota dysbiosis, and have been associated with the occurrence of food allergy. New technologies and experimental tools have provided information regarding the importance of select bacteria on immune tolerance mechanisms. Short-chain fatty acids are crucial metabolic products of gut microbiota responsible for many protective effects against food allergy. These compounds are involved in epigenetic regulation of the immune system. These evidences provide a foundation for developing innovative strategies to prevent and treat food allergy. Here, we present an overview on the potential role of gut microbiota as the target of intervention against food allergy.

Cardiovascular diseases (CVD) are the main cause of death in industrialized countries and are responsible for high economic health care costs. Certain dietary habits can promote alteration of gut microbiota and are causally responsible for heart disease. Elevated plasma levels of choline, betaine, deriving from a protein-enriched diet, are correlated with the progression of atherosclerosis and increased risk for CVD. In contrast, Mediterranean diet and dietary fibers modulating gut microbiota composition and short-chain fatty acids (SCFAs) production exert a protective effect against CVD. The SCFA butyrate has a pivotal role in protecting heart from pathologic hypertrophy and ischemia. Here, we report recent evidence on the importance of diet and of gut microbiota in CVD.

Lactobacillus rhamnosus GG survives in adequate amount after reconstitution of infant formulas according to the Food and Agriculture Organisation (FAO) and World Health Organisation (WHO) recommendations. Our results suggest that an infant formula containing this probiotic could be efficiently used in Countries where FAO/ WHO recommendations are mandatory.

Background: Children with cow's milk allergy (CMA) have an increased risk of other allergic manifestations (AMs). Objective: We performed a parallel-arm randomized controlled trial to test whether administration of an extensively hydrolyzed casein formula (EHCF) containing the probiotic Lactobacillus rhamnosus GG (LGG) can reduce the occurrence of other AMs in children with CMA. Methods: Children with IgE-mediated CMA were randomly allocated to the EHCF or EHCF+LGG groups and followed for 36 months. The main outcome was occurrence of at least 1 AM (eczema, urticaria, asthma, and rhinoconjunctivitis). The secondary outcome was tolerance acquisition, which was defined as the negativization of a double-blind food challenge results at 12, 24, and 36 months. AMs were diagnosed according to standardized criteria. Tolerance acquisition was evaluated every 12 months. Results: A total of 220 children (147 boys [67%]) with a median age of 5.0 months (interquartile range, 3.0-8.0 months) were randomized; 110 children were placed in the EHCF group, and 110 children were placed in the EHCF+LGG group. In the complete case analysis the absolute risk difference for the occurrence of at least 1 AM over 36 months was -0.23 (95% CI, -0.36 to -0.10; P < .001), and the absolute risk difference for the acquisition of cow's milk tolerance was 0.20 (95% CI, 0.05-0.35; P < .01) at 12 months, 0.24 (95% CI, 0.08-0.41; P < .01) at 24 months, and 0.27 (95% CI, 0.11-0.43; P < .001) at 36 months. In the sensitivity analysis the effect size of the main outcome was virtually unchanged when the occurrence of AMs was assigned to all 27 missing children. Conclusions: EHCF+LGG reduces the incidence of other AMs and hastens the development of oral tolerance in children with IgE-mediated CMA.

Introduction the prevalence of malnutrition in children and its impact on clinical outcomes is underrecognized by clinicians in Italy as well as worldwide. A novel definition of pediatric malnutrition has been recently proposed by a working group of the Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.), based on the correlation between illness and the use of zscores of anthropometric measurements. Aim to investigate the prevalence of malnutrition and related nutritional support among hospitalized children in Italy, in a nationwide survey performed in a single day (16/4/2015). Methods an open access website (http://nday.biomedia.net) was used to collected data from 73 hospitals and 101 wards in 14 Italian regions (1994 patients). Anonymous information was collected on hospitals' characteristics, patient's anthropometry, admission diagnosis, presence of chronic diseases and use of nutritional support: oral nutritional supplements (ONS), enteral nutrition (EN) or parenteral nutrition (PN). Z-scores of anthropometric measurements, calculated with Epi Info 7.1.5, defined nutritional status: wasting was identified by BMI or Weight-for-Length z-score (

To investigate whether the addition of the probiotic Lactobacillus rhamnosus GG (LGG) to the extensively hydrolyzed casein formula (EHCF) for cow's milk allergy (CMA) treatment could reduce the occurrence of functional gastrointestinal disorders (FGIDs).This cohort study included children with a positive history for CMA in the first year of life who were treated with EHCF alone or in combination with LGG and had evidence of immune tolerance acquisition to cow's milk for at least 12 months. FGID was diagnosed according to the Rome III diagnostic criteria by investigators unaware of previous treatment. A cohort of consecutive healthy children was also evaluated as a control population.A total of 330 subjects were included, 110 per cohort (EHCF, EHCF+LGG, and healthy controls). The rate of subjects with ≥1 FGID was significantly lower in the EHCF+LGG cohort compared with the EHCF cohort (40% vs 16.4%; P .05). In the EHCF+LGG cohort, a lower incidence was observed for all components of the main study outcome. The prevalence of FGIDs in the healthy cohort was lower than that in the EHCF cohort and similar to that in the EHCF+LGG cohort. The incidence rate ratio of FGIDs for the EHCF+LGG cohort vs the EHCF cohort (0.40; 95% CI, 0.25-0.65; P .001) was unmodified after correction for age at CMA diagnosis, breastfeeding, weaning time, and presence of a first-degree relative with an FGID.These results confirm the increased risk for developing FGIDs in children with CMA and suggest that EHCF+LGG could reduce this risk.

BACKGROUND: DNA methylation of the Th1 and Th2 cytokine genes is altered during cow's milk allergy (CMA). Forkhead box transcription factor 3 (FoxP3) is essential for the development and function of regulatory T cells (Tregs) and is involved in oral tolerance acquisition. We assessed whether tolerance acquisition in children with IgE-mediated CMA is associated with DNA demethylation of the Treg-specific demethylated region (TSDR) of FoxP3. RESULTS: Forty children (aged 3-18 months) were enrolled: 10 children with active IgE-mediated CMA (group 1), 10 children who outgrew CMA after dietary treatment with an extensively hydrolyzed casein formula containing the probiotic Lactobacillus rhamnosus GG (group 2), 10 children who outgrew CMA after treatment with other formulas (group 3), and 10 healthy controls (group 4). FoxP3 TSDR demethylation and expression were measured in mononuclear cells purified from peripheral blood of the four groups of children. FoxP3 TSDR demethylation was significantly lower in children with active IgE-mediated CMA than in either children who outgrew CMA or in healthy children. Formula selection influenced the FoxP3 TSDR demethylation profile. The FoxP3 TSDR demethylation rate and expression level were correlated. CONCLUSIONS: Tolerance acquisition in children with IgE-mediated CMA involves epigenetic regulation of the FoxP3 gene. This feature could be a new target for preventive and therapeutic strategies against CMA.

The long-term effects of amino acid-based formula (AAF) in the treatment of cow's milk allergy (CMA) are largely unexplored. The present study comparatively evaluates body growth and protein metabolism in CMA children treated with AAF or with extensively hydrolyzed whey formula (eHWF), and healthy controls.A 12-month multicenter randomized control trial was conducted in outpatients with CMA (age 5-12 m) randomized in 2 groups, treated with AAF (group 1) and eHWF (group 2), and compared with healthy controls (group 3) fed with follow-on (if age12 months) or growing-up formula (if age12 months). At enrolment (T0), after 3 (T3), 6 (T6), and 12 months (T12) a clinical evaluation was performed. At T0 and T3, in subjects with CMA serum levels of albumin, urea, total protein, retinol-binding protein, and insulin-like growth factor 1 were measured.Twenty-one subjects in group 1 (61.9% boys, age 6.5 ± 1.5 months), 19 in group 2 (57.9% boys, age 7 ± 1.7 months) and 25 subjects in group 3 (48% boys, age 5.5 ± 0.5 months) completed the study. At T0, the weight z score was similar in group 1 (-0.74) and 2 (-0.76), with differences compared to group 3 (-0.17, P 0.05). At T12, the weight z score value was similar between the 3 groups without significant differences. There were no significant changes in protein metabolism in children in groups 1 and 2.Long-term treatment with AAF is safe and allows adequate body growth in children with CMA.

Intolerance to carbohydrates is relatively common in childhood, but still poorly recognized and managed. Over recent years it has come to the forefront because of progresses in our knowledge on the mechanisms and treatment of these conditions. Children with intolerance to carbohydrates often present with unexplained signs and symptoms. Here, we examine the most up-to-date research on these intolerances, discuss controversies relating to the diagnostic approach, including the role of molecular analysis, and provide new insights into modern management in the pediatric age, including the most recent evidence for correct dietary treatment.

Childhood food allergy (FA) rates have rapidly increased with significant direct medical costs for the health care system and even larger costs for the families with a food-allergic child. The possible causes of food allergy become the target of intense scrutiny in recent years. Increasing evidence underline the importance in early life of gut microbiome in the development of allergic diseases. There are a range of factors in the modern environment that may be associated with changes to both the gut microbiome and risk of FA, such as mode of delivery, antibiotic exposure, infant feeding practices, farming environment, and country of origin. Knowledge of the relationship between early life gut microbiome and allergic diseases may facilitate development of novel preventive and treatment strategies. Based on our current knowledge, there are no currently available approved therapies for food allergy. More studies are needed to evaluate the safety and efficacy of allergen-specific and allergen-nonspecific approaches, as well as combination approaches.

A healthy immune system is essential for prevention and recovery in many pediatric illnesses. During last decade, the role of nutrition beyond providing the calories and the macro- and micronutrients for body growth has been well established and clinically proven. Many nutrients have a tremendous potential to modulate directly or indirectly, through a regulation of gut microbiota composition, the development and function of innate and acquired immunity. The potential to modulate the activity of the immune system by interventions with specific nutrients is termed immunonutrition. When we prescribe a particular diet it is important to think that nutrients are not only factors able to influence body growth, but they are also a crucial driving force leading to body health through a regulation of immune system. Within the same category of nutrients it is possible to observe different effects on immune system. As example of this, comparing iso-energetic and iso-proteic doses of different mammalian milks (human milk, donkey milk and bovine milk) we have recently demonstrated, in an animal model, significantly different immunoregulatory and antioxidant properties. These effects are at least in part related to a modification of gut microbiota composition and function, and are able to modulate energy balance, glucose and lipid metabolism. We can modify the immunonutritional properties of a particular food. We have recently demonstrated the possibility through a dietary supplementation with fermented bovine milk with a selected probiotic strain (Lactobacillus paracasei CBA-L74) to significantly reduce the number of common winter infectious diseases in school-age children. This preventive effect derives from a complex network of different mechanisms of action: modulation of gut microbiota composition, stimulation of short chain fatty acids production, stimulation of innate immunity (alpha and beta-defensins, and cathelicidin LL-37 production), stimulation of acquired immunity (secretory IgA), modulation of gut permeability, modulation of epithelial cell growth and differentiation. Significant progress at identifying the gut microbiome has led to a better understanding of the interactions between them and our organs and tissues. Probiotics, while not considered a nutrient, are certainly became a even more frequent component of children diet. The roles that ingested organisms may play in atopic diseases are now potential targets of prevention and treatment.

s / Digestive and Liver Disease 46 (2014) e85–e127 e97 MS was made according to modified Criteria of American Hearth Association. Dietary habits were assessed by a dietician, using the one week alimentary diary. Results: We divided our population in: group A children with WHtR≥0.62 (193pts, age 9.4±2.4 yrs, BMI z-score 2.5±0.5), group B childrenwithWHTR

entire cohort was screened for MS defined according to modified American Heart Association Criteria. For each patient wemeasured WC and calculate Waist to Height ratio (WHtR, WC (cm)/Height (cm)). We used Receiver Operating Characteristic (ROC) curve and Youden Index for detecting the usefulness of this parameter. Results: The prevalence rate of MS was 13.07% (105 pts). Children with MS had meanWHtR of 0.65±0.09. Children without MS presented mean WHtR of 0.62±0.06, this difference was statistically significant (p

Fatty liver disease is a serious complication of childhood obesity. Calorie-restricted regimen (RCR) is one of the e ective therapy for this condition. Aim of the study was to evaluate the effect of lycopene-rich tomato sauce with oregano and basil extracts in obese children with fatty liver on RCR. 61 obese children with fatty liver were enrolled, 52 completed the study. A randomized cross over clinical trial was performed. Participants were assigned to RCR alone or with a supplement of lycopene-rich tomato juice for 60 days; subsequently, the groups were switched to the alternative regimen for the next 60 days. Reduction in BMI, HOMA-IR, cholesterol, triglycerides, liver size, and steatosis was more profound in tomato-supplemented group. Leptin decreased in both groups whereas adiponectin raised only after tomato supplementation. RCR is associated with the impaired engagement of T-cells glycolysis and proliferation, tomato-supplementation resulted in glycolytic metabolic activation of T-cells. Tomato juice ameliorates glucose and lipid metabolism in obese children, improve oxidative and inflammatory state and modulates the mitochondrial metabolism of T-cells contributing to a maintenance of a proper immune surveillance in children, impaired by RCR. The addition of tomato to RCR could be considered a protective and preventive support to obese child. Progetto giovani ricercatori [GR-2016-02363725] dal titolo: "Immune Tolerance, Metabolism and Multiple Sclerosis: Novel Molecular Tools to Monitor Disease Pathogenesis and Progression"