Carmen Di Scala

Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG reduces the occurrence of other allergic manifestations in children with cow's milk allergy: 3-year randomized controlled trial

Background Children with cows 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 cows 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.

The Influence of Early Life Nutrition on Epigenetic Regulatory Mechanisms of the Immune System

The immune system is exquisitely sensitive to environmental changes. Diet constitutes one of the major environmental factors that exerts a profound effect on immune system development and function. Epigenetics is the study of mitotically heritable, yet potentially reversible, molecular modifications to DNA and chromatin without alteration to the underlying DNA sequence. Nutriepigenomics is an emerging discipline examining the role of dietary influences on gene expression. There is increasing evidence that the epigenetic mechanisms that regulate gene expression during immune differentiation are directly affected by dietary factors or indirectly through modifications in gut microbiota induced by different dietary habits. Short-chain fatty acids, in particular butyrate, produced by selected bacteria stains within gut microbiota, are crucial players in this network.

Diagnosing and Treating Intolerance to Carbohydrates in Children

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.

The Controversial Role of Food Allergy in Infantile Colic: Evidence and Clinical Management

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.

Gut Microbiota as a Target for Preventive and Therapeutic Intervention against Food Allergy

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.

Amino acid-based formula in cow's milk allergy : Long-term effects on body growth and protein metabolism

Objectives: The long-term effects of amino acid–based formula (AAF) in the treatment of cows 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. Methods: 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 age <12 months) or growing-up formula (if age >12 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. Results: 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. Conclusion: Long-term treatment with AAF is safe and allows adequate body growth in children with CMA.

Food Allergies: Novel Mechanisms and Therapeutic Perspectives

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.

Gut microbiota composition and butyrate production in children affected by non-IgE-mediated cow’s milk allergy

Cow’s milk allergy (CMA) is one of the earliest and most common food allergy and can be elicited by both IgE- or non-IgE-mediated mechanism. We previously described dysbiosis in children with IgE-mediated CMA and the effect of dietary treatment with extensively hydrolyzed casein formula (EHCF) alone or in combination with the probiotic Lactobacillus rhamnosus GG (LGG). On the contrary, the gut microbiota in non-IgE-mediated CMA remains uncharacterized. In this study we evaluated gut microbiota composition and fecal butyrate levels in children affected by non-IgE-mediated CMA. We found a gut microbiota dysbiosis in non-IgE-mediated CMA, driven by an enrichment of Bacteroides and Alistipes. Comparing these results with those previously obtained in children with IgE-mediated CMA, we demonstrated overlapping signatures in the gut microbiota dysbiosis of non-IgE-mediated and IgE-mediated CMA children, characterized by a progressive increase in Bacteroides from healthy to IgE-mediated CMA patients. EHCF containg LGG was more strongly associated with an effect on dysbiosis and on butyrate production if compared to what observed in children treated with EHCF alone. If longitudinal cohort studies in children with CMA will confirm these results, gut microbiota dysbiosis could be a relevant target for innovative therapeutic strategies in children with non-IgE-mediated CMA.

The Influence of Fiber on Gut Microbiota: Butyrate as Molecular Player Involved in the Beneficial Interplay Between Dietary Fiber and Cardiovascular Health

Abstract 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.

The Importance of immunonutrition in children

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.