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Abstract Background To assess the adverse food reactions (AFR) prevalence in children with autism spectrum disorder (ASD) and in non-ASD healthy controls (NASD). Nutritional status alterations, food selectivity and adherence to Mediterranean Diet (MD) were also evaluated. Methods The NAFRA (Nutritional status and Adverse Food Reactions in children with Autism Spectrum Disorder) project was an observational, case-control, comparative study conducted at a tertriary center for pediatrics involving Caucasian patients of both sexes, aged 18 months-7 years, with a diagnosis of ASD, and matched NASD controls. Results From October 2017 to December 2023, 100 ASD patients [79 male, mean (± SD) age 49.9 months (± 15.4)] and 100 NASD controls [75 male, mean (± SD) age 49.8 months (± 17.7)] were enrolled at the Pediatric Section of the Department of Translational Medical Science of the University of Naples Federico II. A significantly higher prevalence of AFR was observed in ASD patients if compared with NASD (16% vs. 2%, p = 0.001), mainly due to a higher prevalence of food allergy (7% vs. 1%, p = 0.03). A significantly higher prevalence of food intolerance and celiac disease was also observed in ASD children. The rate of obesity was significantly higher in ASD patients compared to NASD. Food selectivity and low MD-adherence were more frequent in ASD children (26% vs. 2%, p

Increasing evidence suggests that alterations in the gut microbiome (GM) play a pivotal role in the pathogenesis of pediatric food allergy (FA). This scoping review analyzes the current evidence on GM features associated with pediatric FAs and highlights the importance of the GM as a potential target of intervention for preventing and treating this common condition in the pediatric age. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we searched PubMed and Embase using the keywords (gut microbiome OR dysbiosis OR gut microbiota OR microbiome signatures) AND (food allergy OR IgE-mediated food allergy OR food protein-induced allergic proctocolitis OR food protein-induced enterocolitis OR non-IgE food allergy OR cow milk allergy OR hen egg allergy OR peanut allergy OR fish allergy OR shellfish allergy OR tree nut allergy OR soy allergy OR wheat allergy OR rice allergy OR food sensitization). We included 34 studies reporting alterations in the GM in children affected by FA compared with healthy controls. The GM in pediatric FAs is characterized by a higher abundance of harmful microorganisms (e.g., Enterobacteriaceae, Clostridium sensu stricto, Ruminococcus gnavus, and Blautia spp.) and lower abundance of beneficial bacteria (e.g., Bifidobacteriaceae, Lactobacillaceae, some Bacteroides species). Moreover, we provide an overview of the mechanisms of action elicited by these bacterial species in regulating immune tolerance and of the main environmental factors that can modulate the composition and function of the GM in early life. Altogether, these data improve our knowledge of the pathogenesis of FA and can open the way to innovative diagnostic, preventive, and therapeutic strategies for managing these conditions.

Background: Updated epidemiologic data are important for defining effective public health strategies for pediatric food allergy (FA). Objective: The Epidemiology of Paediatric Italian Food Allergy (EPIFA) study was designed to investigate the epidemiology of pediatric FA in one of the most heavily populated Italian regions. Methods: A retrospective cohort study was performed in collaboration with family pediatricians aimed at investigating the epidemiology of Italian pediatric FA during 2009 to 2021. Family pediatricians in the Campania region were invited to use the Google Forms platform for online compilation of data forms. Data forms were reviewed by experienced pediatric allergists at the coordinating center. Results: A total population of 105,151 subjects (aged 0-14 years) was screened during the study period. Data from 752 FA patients were evaluated. A progressive increase in FA incidence and prevalence was observed from 2009 to 2021, with a relative increase up to 34% and 113.6%, respectively, at the end of study period. The relative increase in FA prevalence was higher in the 0-3-year-old age group in the same study period (+120.8%). The most frequent allergens were cow’s milk, hen’s egg, and nuts. Conclusion: The results of the EPIFA study showed an increase in pediatric FA incidence and prevalence from 2009 to 2021 in Italy. These results underline the necessity of new effective strategies for preventing and managing these conditions.

Abstract The increased intake of ultraprocessed foods (UPFs) in the pediatric age paralleled with the risen prevalence of childhood obesity. The Ultraprocessed Foods in Obesity (UFO) Project aimed at investigating the potential mechanisms for the effects of UPFs in facilitating pediatric obesity, focusing on the direct role of advanced glycation end-products (AGEs) on mitochondrial function, the key regulator of obesity pathophysiology. We comparatively investigated the daily dietary intake of UPFs, energy, nutrients, dietary AGEs [Nε -(carboxymethyl)lysine (CML), Nε -(1-carboxyethyl)lysine (CEL), and Nδ -(5-hydro-5- methyl-4-imidazolon-2-yl)-ornithine (MG-H1)] in 53 obese patients and in 100 healthy controls visiting the Tertiary Center for Pediatric Nutrition of the Department of Translational Medical Science at the University of Naples “Federico II”. AGEs skin accumulation and mitochondrial function in peripheral blood mononuclear cells (PBMCs) were also assessed. A higher intake of UPFs and AGEs, energy, protein, fat, and saturated fatty acids was observed in obese patients. Obese children presented significantly higher skin AGEs accumulation and alterations in mitochondrial metabolism. PBMCs from healthy controls exposed to AGEs showed the same mitochondrial alterations observed in patients. These findings support the UPFs role in pediatric obesity, and the need for dietary strategies limiting UPFs exposure for obesity prevention and treatment.

Food allergy (FA) represents one of the main chronic conditions of the pediatric population. The gut microbiome (GM)-immune system axis is a milestone in affecting FA susceptibility. The dynamic and bidirectional crosstalk between the GM and immune system starts early in life, and it is deeply modulated during the first 1,000 days of life. Nutritional factors during this crucial period mainly influence the proper GM-immune system development and function across the lifespan, with potential beneficial or detrimental effects on health status. Immunonutrition strategies, applied from conception, could represent an innovative target for prevention and treatment of pediatric FA. Here we described the potential role of preventive and therapeutic immunonutrition strategies for pediatric FA, highlighting putative future perspectives in this field.

IntroductionMaternal diet during pregnancy has been linked to offspring allergy risk and it could represent a potential target for allergy prevention. The Mediterranean Diet (MD) is considered one of the healthiest dietary models. Randomized-controlled trials on the effect of MD in preventing pediatric allergic diseases are still needed.Methods and analysisThe Mediterranean Diet during Pregnancy study (PREMEDI) will be a 9-month multi-center, randomized-controlled, parallel groups, prospective trial. Healthy women (20–35 years) at their first trimester of pregnancy at risk for atopy baby, will be randomly allocated to Group 1 (standard obstetrical and gynecological follow-up and nutritional counseling to promote MD) or Group 2 (standard obstetrical and gynecological follow-up alone). 138 mother-child pair per group will be needed to detect a reduction in cumulative incidence of ≥1 allergic disease at 24 months of age. The primary study aim will be the evaluation of the occurrence of allergic disorders in the first 24 months of life. The secondary aims will be the evaluation of maternal weight gain, pregnancy/perinatal complications, growth indices and occurrence of other chronic disorders, mother-child pair adherence to MD and gut microbiome features, breastfeeding duration and breast milk composition, epigenetic modulation of genes involved in immune system, and metabolic pathways in the offspring.Ethics and disseminationThe study protocol has been approved by the Ethics Committee of the University of Naples Federico II (number 283/21) and it will be conducted in accordance with the Helsinki Declaration (Fortaleza revision, 2013), the Good Clinical Practice Standards (CPMP/ICH/135/95), the Italian Decree-Law 196/2003 regarding personal data and the European regulations on this subject. The study has been registered in the Clinical Trials Protocol Registration System.Clinical trial registration[http://clinicaltrials.gov], identifier [NCT05119868].

BackgroundAmino acid-based formula (AAF) is a relevant dietary option for non-breastfed children. The present study was designed to evaluate the body growth pattern in cow's milk protein allergy (CMPA) children treated for 6 months with a new AAF.MethodsThis was an open-label, single arm study evaluating body growth pattern in immunoglobulin E (IgE)-mediated CMPA infants receiving a new AAF for 6 months. The outcomes were anthropometry (weight, length, head circumference), adherence to the study formula and occurrence of adverse events (AEs).ResultsFifteen children [all Caucasian and born at term; 53.3% born with spontaneous delivery; 80% male; 80% with familial allergy risk; mean age (±SD) 3 ± 2.5 months at IgE-mediated CMPA diagnosis; mean age (±SD) 16.7 ± 5.9 months at enrolment, mean total serum IgE (±SD) 298.2 ± 200.4 kU/L] were included and completed the 6-month study. Data from fifteen age- and sex-matched healthy controls were also adopted as comparison. At baseline, all CMPA patients were weaned and were receiving the new AAF. All 15 patients completed the 6-month study period. For the entire CMPA pediatric patients’ cohort, from baseline to the end of the study period, the body growth pattern resulted within the normal range of World Health Organization (WHO) growth references and resulted similar to healthy controls anthropometric values. The formula was well tolerated. The adherence was optimal and no AEs related to AAF use were reported.ConclusionsThe new AAF ensured normal growth in subjects affected by IgE-mediated CMPA. This formula constitutes another suitable safe option for the management of pediatric patients affected by CMPA.

Abstract 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 ).

Postbiotics are commonly defined as preparations of inanimate probiotics and/or their cellular components and/or their metabolites/end products that confer health benefits on the host. They have been suggested as a promising strategy to limit infectious diseases. Emerging evidence support the efficacy of the postbiotic derived from cow’s milk fermentation with the probiotic Lacticaseibacillus paracasei CBAL74 (FM-CBAL74) in preventing pediatric infectious diseases. We aimed at reviewing the evidence available.

Chronic migraine is a burdensome disease presenting with episodic pain and several symptoms that may persist even among headache attacks. Multisensory integration is modified in migraine, as assessed by the level of the perception of sound-induced flash illusions, a simple paradigm reflecting changes in cortical excitability which reveals to be altered in migraineurs. OnabotulinumtoxinA is an effective preventive therapy for chronic migraineurs, reducing peripheral and central sensitization, and may influence cortical excitability. Patients affected by chronic migraine who started onabotulinumtoxinA preventive therapy were included. Clinical effects (headache diaries and migraine related questionnaires) were assessed at the beginning of the therapy and after 12 weeks. Contextually, patients underwent the evaluation of multisensory perception by means of the sound-induced flash illusions. OnabotulinumtoxinA showed effectiveness both in migraine prevention and in reducing headache burden. Even one session of therapy was able to restore, at least partially, multisensory processing, as shown by patients’ susceptibility to the sound-induced flash illusion. OnabotulinumtoxinA could influence migraineurs cortical excitability concurrently to the beneficial effects in headache prevention.

Cow's milk allergy (CMA) is one of the most common food allergies and one of the main causes of food-induced anaphylaxis in the pediatric age. Moreover, up to 45% of CMA children develop other atopic manifestations later in life, a phenomenon commonly named atopic march. Thus, CMA imposes a significant cost to health care systems as well as to families, and has emerged as one of the most expensive allergic diseases. The immunonutrition strategy builds its foundation on the ability of selected dietary factors to modulate immune system development and function. Recent studies highlighted the potential of immunonutrition in the management of CMA. This review is focused on the mechanisms and long-term clinical outcomes of the immunonutrition approach in children with CMA.

Human skin is the largest organ and the most external interface between the environment and the body. Vast communities of viruses, bacteria, archaea, fungi, and mites, collectively named the skin microbiome (SM), cover the skin surface and connected structures. Skin-resident microorganisms contribute to the establishment of cutaneous homeostasis and can modulate host inflammatory responses. Imbalances in the SM structure and function (dysbiosis) are associated with several skin conditions. Therefore, novel target for the skincare field could be represented by strategies, which restore or preserve the SM natural/individual balance. Several of the beneficial effects exerted by the SM are aroused by the microbial metabolite butyrate. Since butyrate exerts a pivotal role in preserving skin health, it could be used as a postbiotic strategy for preventing or treating skin diseases. Herein, we describe and share perspectives of the potential clinical applications of therapeutic strategies using the postbiotic butyrate against human skin diseases.

Intake of a postbiotic product can support immunity depending on specific conditions of the consumer. The present study evaluates the potential impact of baseline values on the change of various immune factors (α-defensin, β-defensin, cathelicidin, and secretory IgA) after three months of consumption of a postbiotic based on cow’s milk fermented with Lactobacillus paracasei CBA L74 in a young population. For the analysis, raw data of three studies were used in a multivariate analysis applying confounding factors. One study in newborns demonstrated that intake of the postbiotic yielded an increase in the concentrations of α-defensin and secretory IgA (at least p < 0.02), while for all factors, except β-defensin, the higher the baseline values the lower the increase (at least p < 0.002). Two combined studies in young children (aged 1–4 years) showed an increase in the concentration of all factors after intake of the postbiotic (at least p < 0.003), but now showing the higher the baseline values the higher the increase after three months (at least p < 0.02) in only the postbiotic group. It is concluded that consumption of the postbiotic leads to a baseline- and age-dependent increase in the concentrations of the immune factors under study in both newborns and young children. It is hypothesized that maturation of the immune system leads to different effects on optimizing host defense factors via this postbiotic intake.

Human skin is colonized by diverse commensal microbes, making up the skin microbiota (SM), contributing to skin integrity and homeostasis. Many of the beneficial effects aroused by the SM are exerted by microbial metabolites such as short-chain fatty acids (SCFAs), including butyric acid. The SCFAs can be used in cosmetic formulations against skin diseases to protect SM by preserving and/or restoring their natural balance. Unpleasant sensorial properties and unfavorable physico-chemical properties of butyrate strongly limit its cosmetic use. In contrast, some butyrate derivatives, including phenylalanine butyramide (C13H18N2O2, FBA), a solid form of butyric acid, are odorless while retaining the pharmacokinetic properties and safety profile of butyric acid. This study assessed the FBA’s permeation across the skin and its soothing and anti-reddening potential to estimate its cosmetic application. The dosage method used to estimate FBA’s levels was validated to be sure of analytical results. The FBA diffusion tests were estimated in vitro using a Franz-type vertical diffusion cell. The soothing action was evaluated in vivo by Colorimeter CL400, measuring the erythema index. The results suggest that the FBA represents an innovative way to exploit the benefits of butyric acid in the cosmetic fields since it cannot reach the bloodstream, is odorless, and has a significative soothing action (decrease the erythema index −15.7% after 30′, and −17.8% after 60′).

Worldwide obesity is a public health concern that has reached pandemic levels. Obesity is the major predisposing factor to comorbidities, including type 2 diabetes, cardiovascular diseases, dyslipidemia, and non-alcoholic fatty liver disease. The common forms of obesity are multifactorial and derive from a complex interplay of environmental changes and the individual genetic predisposition. Increasing evidence suggest a pivotal role played by alterations of gut microbiota (GM) that could represent the causative link between environmental factors and onset of obesity. The beneficial effects of GM are mainly mediated by the secretion of various metabolites. Short-chain fatty acids (SCFAs) acetate, propionate and butyrate are small organic metabolites produced by fermentation of dietary fibers and resistant starch with vast beneficial effects in energy metabolism, intestinal homeostasis and immune responses regulation. An aberrant production of SCFAs has emerged in obesity and metabolic diseases. Among SCFAs, butyrate emerged because it might have a potential in alleviating obesity and related comorbidities. Here we reviewed the preclinical and clinical data that contribute to explain the role of butyrate in this context, highlighting its crucial contribute in the diet-GM-host health axis.