Allergic Infants Research Articles

Impaired calcium influx underlies skewed T helper cell differentiation in children with IgE-mediated food allergies.

Reasons for Th2 skewing in IgE-mediated food allergies remains unclear. Clinical observations suggest impaired T cell activation may drive Th2 responses evidenced by increased atopic manifestations in liver transplant patients on tacrolimus (a calcineurin inhibitor). We aimed to assess differentiation potential, T cell activation and calcium influx of naïve CD4+ T cells in children with IgE-mediated food allergies. Peripheral blood mononuclear cells from infants in the Starting Time for Egg Protein (STEP) Trial were analyzed by flow cytometry to assess Th1/Th2/Treg development. Naïve CD4+ T cells from children with and without food allergies were stimulated for 7 days to assess Th1/Th2/Treg transcriptional factors and cytokines. Store operated calcium entry (SOCE) was measured in children with and without food allergies. The effect of tacrolimus on CD4+ T cell differentiation was assessed by treating stimulated naïve CD4+ T cells from healthy volunteers with tacrolimus for 7 days. Egg allergic infants had impaired development of IFNγ+ Th1 cells and FoxP3+ transitional CD4+ T cells compared with non-allergic infants. This parallels reduced T-bet, IFNγ and FoxP3 expression in naïve CD4+ T cells from food allergic children after invitro culture. SOCE of naïve CD4+ T cells was impaired in food allergic children. Naïve CD4+ T cells treated with tacrolimus had reduced IFNγ, T-bet, and FoxP3, but preserved IL-4 expression. In children with IgE-mediated food allergies, dysregulation of T helper cell development is associated with impaired SOCE, which underlies an intrinsic impairment in Th1 and Treg differentiation. Along with tacrolimus-induced Th2 skewing, this highlights an important role of SOCE/calcineurin pathway in T helper cell differentiation.

The Cost-Effectiveness of Omalizumab for Treatment of Food Allergy

Omalizumab is an anti-IgE therapy newly approved by the Food and Drug Administration for allergen agnostic treatment of single or multiple food allergies in patients aged 1 year or older. Evaluate the cost-effectiveness of omalizumab as a food allergy treatment. We evaluated health and economic outcomes in Markov cohorts of simulated food allergic infants randomized to receive omalizumab using a 15-year horizon. Monte Carlo simulation was used (n= 40,000 subjects) to evaluate cost-effectiveness from a societal perspective, incorporating both a family-level and individual-level analysis. We included family-level analysis to incorporate a broad perspective for health utility change, given treatment effects likely benefit all parties at home (eg, caregivers, siblings), not just the patient, representing the sum of changes in all such persons. Supplemental analyses explored lower omalizumab cost and home initiation. We performed deterministic and probabilistic sensitivity analyses. In the family-level cohort analysis, omalizumab exceeded cost-effectiveness thresholds ($185,183/quality-adjusted life-years [QALY]). In a comparison of the omalizumab strategy (OMA) with the non-omalizumab strategy, the cost of OMA exceeded the non-omalizumab strategy ($315,020 vs $136,609) with greater incremental effectiveness (12.668 vs 11.699 QALY). In the individual-level analysis, the cost-effectiveness of OMA was $573,698/QALY. In base-case assessments, OMA was cost-effective (willingness to pay, $100,000/QALY) at a health state utility (HSU) improvement of 0.265. The value-based cost of OMA ranged from $14,166 to $23,791 when it was considered at the individual and family-unit levels. Requiring OMA administration in the clinic was not cost-effective (incremental cost-effectiveness ratio, $260,239). In the base case and at current pricing, omalizumab is not cost-effective, but it could be at a lower retail price or when use creates large health utility shifts in the family and patient.

Impact of processing on the sensitising capacity and cross-reactivity of cow's and camel milk proteins in a Brown Norway rat study

Infant formulas based on hydrolysed cow's milk proteins are used when breastfeeding is not feasible in cow's milk allergic infants. Camel milk has been shown to be well-tolerated by the majority of children with cow's milk allergy (CMA) and may be a substitute in management of CMA. Here we aimed to evaluate the impact of processing on immunogenicity, sensitising, antibody-binding and cross-reactive capacity of cow's and camel milk.Cow's and camel milk were processed by means of enzyme hydrolysis or heat treatment. Brown Norway rats were immunised with PBS, non-processed, enzyme hydrolysed or heat-treated cow's or camel milk. In vivo tests were performed for evaluation of clinical signs. Blood and faecal samples were analysed for levels and specificity of antibody responses.Cow's and camel milk showed similar sensitising capacity. Processing decreased the sensitising capacity of cow's milk, yet only enzyme hydrolysis but not heat treatment decreased the sensitising capacity of camel milk. Processing affected the specificity of antibodies raised in the rats, though the effect differed between cow's and camel milk. The study showed a low cross-reactivity between cow's and camel milk, which was decreased with processing, suggesting that processing of camel milk may improve its usefulness in CMA management.

Consumption of cow's milk formula in the nursery and the development of milk allergy.

The effect of the amount of transient cow's milk formula (CMF) consumed during the first days of life on IgE-cow's milk allergy (IgE-CMA) is unknown. A cohort of 58 patients with IgE-CMA was identified from a large scale population-based study of 13,019 infants followed from birth. A group of 116 infants matched for sex and breastfeeding only duration (beyond the nursery period), and another random group of 259 healthy infants were used as controls. Parents were interviewed and the infants' medical records were searched to assess CMF consumption in the nursery. While 96% of the mothers of the 174 infants (58 with Cow's milk allergy and 116 controls) reported on exclusive breastfeeding during the stay in the nursery, CMF consumption was documented in 96 (55%) of the infants. Of those, most (57; 59%) received one to three feedings, 20 (21%) received four to nine feedings, and 19 (20%) received ≥10 feedings. Fewer formula feeds (1-3) were significantly more common in the allergic group than ≥4 feeds (p=0.0003) and no feeds at all (p=0.02) compared to controls (n=116). Of those exclusively breastfed in the nursery, 13/23 allergic infants (57%) introduced CMF at age 105-194days (the period with highest-risk for IgE-CMA) compared to 33/98 (34%) from the random control group (n=259) (p=0.04). Most infants end up receiving few CMF feeds in the nursery. Transient CMF in the nursery is associated with increased risk of IgE-CMA.

Development of a Two-Step Hydrolysis Hypoallergenic Cow's Milk Formula and Evaluation of Residue Allergenicity by Peptidomics and Immunoreactivity Analysis.

Cow's milk allergy (CMA) is an abnormal immune response that severely affects the nutritional supplementation of allergic infants. Currently, only a limited number of hypoallergenic formulas are available on the market, and these are only categorized according to their degree of hydrolysis, which still poses an allergy risk and cannot be consumed by CMA patients, especially infants. To address this issue, we developed a two-step hydrolysis hypoallergenic formula targeting destruction of allergen epitope from whey protein. Then, a comprehensive evaluation system was constructed, including peptidomics analysis, in vivo and in vitro allergenicity assessments, revealing allergic changes in the product from the epitope structure level to the immunological level. The results showed that 97.14% of hydrolyzed peptides from α-lactalbumin and β-lactoglobulin did not contain allergenic epitopes after treatment with trypsin and flavourzyme. In vitro and in vivo allergenicity assessment results confirmed that the two-step hydrolysis method effectively reduced the allergenicity of whey protein. Compared with the common milk powder, the hypoallergenic formula induced lower levels of basophil degranulation and relieved the body's anaphylactic symptoms caused by cow milk. This study provides a promising solution to the limited hypoallergenic formula problem and may benefit allergic infants who require nutritional supplements.

Effects of a new amino acid, rice glucose polymer-based, and commercial amino acid-based formulas on growth and protein status of infants with cow's milk protein allergy.

Infants with cow's milk protein allergy (CMPA) are at risk for nutrient inadequacy and impaired growth. To evaluate the effect of a new amino acid-based formula (nAAF) compared with commercial amino acid-based formula (cAAF) on growth and protein status of cow's milk protein (CMP)-allergic infants and to compare their growth with those of healthy infants. Infants less than 6 months of age with CMPA were enrolled in the nAAF or cAAF groups. Healthy infants fed breast milk (BM) or infant formula (IF) were controls. They remained on their formula/milk until day 28 of the study. Anthropometric evaluation was performed at birth, day 0 and day 28 of the study and calculated to z-scores of weight-for-age (WAZ), length-for-age (LAZ) and head circumference-for-age (HAZ). Plasma amino acids, albumin, urea nitrogen, and creatinine were assessed for infants with CMPA on day 0 and day 28. The nAAF and cAAF groups did not differ in increases in WAZ [regression coefficient (95%CI): 0.088 (-0.619, 0.796), p = 0.791], LAZ [0.045 (-0.789, 0.880, p = 0.909], and HAZ [-0.645 (-2.082, 0.793), p = 0.337] between day 0 and day 28. The increases in WAZ and LAZ during 28 days in the nAAF group did not differ from the controls. The changes in the blood chemistry values, except albumin, were not different between CMPA groups. The nAAF, similar to the cAAF, supports growth and protein status for infants with CMPA, and it might be used as a substitute for the cAAF.

The methylation profile of IL4, IL5, IL10, IFNG and FOXP3 associated with environmental exposures differed between Polish infants with the food allergy and/or atopic dermatitis and without the disease.

Epigenetic dynamics has been indicated to play a role in allergy development. The environmental stimuli have been shown to influence the methylation processes. This study investigated the differences in CpGs methylation rate of immune-attached genes between healthy and allergic infants. The research was aimed at finding evidence for the impact of environmental factors on methylation-based regulation of immunological processes in early childhood. The analysis of methylation level of CpGs in the IL4, IL5, IL10, IFNG and FOXP3 genes was performed using high resolution melt real time PCR technology. DNA was isolated from whole blood of Polish healthy and allergic infants, with food allergy and/or atopic dermatitis, aged under six months. The significantly lower methylation level of FOXP3 among allergic infants compared to healthy ones was reported. Additional differences in methylation rates were found, when combining with environmental factors. In different studied groups, negative correlations between age and the IL10 and FOXP3 methylation were detected, and positive - in the case of IL4. Among infants with different allergy symptoms, the decrease in methylation level of IFNG, IL10, IL4 and FOXP3 associated with passive smoke exposure was observed. Complications during pregnancy were linked to different pattern of the IFNG, IL5, IL4 and IL10 methylation depending on allergy status. The IFNG and IL5 methylation rates were higher among exclusively breastfed infants with atopic dermatitis compared to the non-breastfed. A decrease in the IFNG methylation was noted among allergic patients fed exclusively with milk formula. In different study groups, a negative correlation between IFNG, IL5 methylation and maternal BMI or IL5 methylation and weight was noted. Some positive correlations between methylation rate of IL10 and child's weight were found. A higher methylation of IL4 was positively correlated with the number of family members with allergy. The FOXP3 methylation in allergic infants was lower than in the healthy ones. The methylation profile of IL4, IL5, IL10, IFNG and FOXP3 associated with environmental exposures differed between the studied groups. The results offer insights into epigenetic regulation of immunological response in early childhood.

Further Insights into the Gut Microbiota of Cow's Milk Allergic Infants: Analysis of Microbial Functionality and Its Correlation with Three Fecal Biomarkers.

Cow's milk allergy (CMA) is one of the most prevalent food allergies in children. Several studies have demonstrated that gut microbiota influences the acquisition of oral tolerance to food antigens at initial stages of life. Changes in the gut microbiota composition and/or functionality (i.e., dysbiosis) have been linked to inadequate immune system regulation and the emergence of pathologies. Moreover, omic sciences have become an essential tool for the analysis of the gut microbiota. On the other hand, the use of fecal biomarkers for the diagnosis of CMA has recently been reviewed, with fecal calprotectin, α-1 antitrypsin, and lactoferrin being the most relevant. This study aimed at evaluating functional changes in the gut microbiota in the feces of cow's milk allergic infants (AI) compared to control infants (CI) by metagenomic shotgun sequencing and at correlating these findings with the levels of fecal biomarkers (α-1 antitrypsin, lactoferrin, and calprotectin) by an integrative approach. We have observed differences between AI and CI groups in terms of fecal protein levels and metagenomic analysis. Our findings suggest that AI have altered glycerophospholipid metabolism as well as higher levels of lactoferrin and calprotectin that could be explained by their allergic status.

Mass cytometry analysis of blood from peanut-sensitized tolerant and clinically allergic infants

IgE-mediated food allergies in infants are a significant health concern, with peanut allergy being of particular interest due to its prevalence and severity. Among individuals who produce peanut-specific IgE some experience no adverse reaction on peanut consumption. This asymptomatic phenotype is known as sensitized tolerance. To elucidate the immune environment of peanut sensitized tolerant and clinically allergic one-year-olds, high-dimensional mass cytometry was conducted as part of the HealthNuts study. The resulting data includes peripheral blood mononuclear cells from 36 participants encompassing non-allergic, peanut sensitized with tolerance, and clinically peanut allergic infants. The raw mass cytometry data is described here and freely available for reuse through the Immunology Database and Analysis Portal (ImmPort). Additional allergy information and serum vitamin D levels of the participants were measured and are also included in the data upload. These high-dimensional mass cytometry data, when combined with clinical information, offer a broad immune profile of peanut allergic and sensitized tolerant infants.

Alterations of the gut microbiota and short chain fatty acids in necrotizing enterocolitis and food protein-induced allergic protocolitis infants: A prospective cohort study.

Even though presenting with similar clinical manifestations, necrotizing enterocolitis (NEC) and food protein-induced allergic protocolitis (FPIAP) have completely different treatments and prognosis. Our study aimed to quantify and evaluate differences in gut microbiota and short chain fatty acids (SCFAs) between infants with NEC and FPIAP to better identify these two diseases in clinical settings. A total of 43 infants with NEC or FPIAP in Children's Hospital of Chongqing Medical University, China between December 2020 and December 2021 were enrolled. Stool samples were prospectively collected and froze. Infants defined as NEC were those who presented with clinical courses consistent with NEC and whose radiographs fulfilled criteria for Bell's stage 2 or 3 NEC, while those who were healthy in appearance and had blood in the stool (visible or may be microscopic), had normal bowel sounds in physical examination, were resolved after eliminating the causative food, and/or had recurrence of symptoms after oral food challenge (OFC) were defined as FPIAP. Primers specific for bacterial 16S rRNA genes were used to amplify and pyrosequence fecal DNA from stool samples. Gas chromatography-mass spectrometry (GC-MS) technology was used to determine the concentrations of SCFAs. Among the 43 infants, 22 were diagnosed with NEC and 21 were diagnosed with FPIAP. The microbial community structure in NEC infant stools differed significantly from those in FPIAP infant stools. NEC infants had significantly higher proportion of Actinobacteria and reduced proportion of Bacteroidetes compared with FPIAP infants, and the proportions of Halomonas, Acinetobacter, Bifidobacterium, and Stenotrophomonas in NEC infants were significantly higher than that of FPIAP infants. In addition, infants with NEC had significantly lower levels of acetic acid, propionic acid, butyric acid, isovaleric acid, and total SCFAs, and higher level of hexanoic acid as compared to the infants of the FPIAP group. The differences of gut microbiota composition and concentrations of SCFAs might represent suitable biomarker targets for early identification of NEC and FPIAP.

Development Sangyod rice protein-based formula for cow milk allergic infant and its gut microbiota modulation

Background: In Thailand, cow milk allergies are the leading food allergy in infants. Rice protein is one of the hypoallergenic food ingredients used as an alternative plant-based protein in nutritional products. Sangyod rice (Oryza sativa, L., var. indica), found in southern Thailand, has been reported to contain a high content of nutrients. Isomaltooligosaccharides (IMO) are accepted as prebiotics and are applicable as food ingredients to enhance the physiochemical quality of foods as a sweetener, and can also have physiological functions including the enhancement of gut microflora. The supplementation of formulas with prebiotics will support a mature immune system and intestinal colonization of infants. Objectives: This research aimed to develop Sangyod rice protein-based infant formula for cow milk allergic infants, evaluated its nutritional composition, sensory, and anti-allergenic activity, and investigated the effects of the formula on gut microbiota modulation. Materials and methods: The development of infant formula based on Sangyod rice protein and fortified with IMO from Sangyod rice flour was studied on nutrition composition, microbiology, anti-allergenic activity, and effect on gut microbiota. These properties reflect quality and safety to meet requirements of infant and follow-up formula.Results:The energy of Sangyod rice-protein-based formula was 67 kcal per 100 ml. The results indicated that the formula met the requirements of macronutrients providing 3.03 g of protein, 4.37 g of fat, and 13.26 g of carbohydrate, and passed on total bacteria contamination. Surprisingly, the developed formulas showed higher results in an anti-allergenic activity test (86.98±5.49%) by inhibition on the release of β-hexosaminidase enzyme in RBL-2H3 cells compared to a commercial hypoallergenic formula. The addition of prebiotic (IMO) significantly increased populations of Lactobacillus (10.7 log cell/ml) within 24 hours (p<0.05) compared with commercial product. This result affected the production of shot chain fatty acids (SCFAs) by increasing the amount of acetic acid and propionic acid but had no effect on lactic acid and butyric acid production. This result may have a beneficial effect on the immune system and hopefully can help to prevent or decrease risk of cow milk allergy. The sensory evaluation of Sangyod rice protein-based formula showed the highest scores in test (6.34±1.39), odor (6.74±1.15), and overall acceptability (6.52±1.26), but had no significant differences (p<0.05) compared to commercial hypoallergenic formula.Conclusion: The Sangyod rice protein-based formula can compete and was acceptable for the hypoallergenic formula and would be an option for substituting cow milk in the treatment of cow milk protein allergy. However, this study is the first step to develop the hypoallergenic formula and still needs the preclinical testing and clinical study in the future to claim as a hypoallergenic formula. Keywords: Sangyod rice, Infant formula, rice protein-based formula, hypoallergenic formula

Hypoallergenicity assessment of an extensively hydrolyzed whey-protein formula in cow's milk allergic infants.

Background Extensively hydrolyzed formulas are recommended for the dietary management of infants with cow's milk allergy (CMA).ObjectivesHypoallergenicity, growth, and gastrointestinal (GI) tolerability of a new extensively hydrolyzed whey‐protein formula (eHWF) in CMA children were assessed.MethodsIn this prospective, randomized, international, multi‐center study (Trial NL3889), 34 children with confirmed CMA (74% IgE‐mediated) underwent a double‐blind, placebo‐controlled food challenge (DBPCFC) with an eHWF developed with non‐porcine enzymes, supplemented with prebiotic short‐chain galacto‐ and long‐chain fructo‐oligosaccharides (0.8 g/L, ratio 9:1), arachidonic acid (0.35/100 g), and docosahexaenoic acid (0.35/100 g). If tolerant to the eHWF, children participated in a 7‐day open food challenge with this eHWF. Anthropometrics and GI tolerability were assessed in an optional 16‐weeks follow‐up.ResultsOf the 34 children who started the DBPCFC with the eHWF, 25 subjects (19 boys, mean age: 61 weeks, 18 with IgE‐mediated CMA) completed the DBPCFC and 7‐day open challenge without major protocol deviations and tested negative at both challenges. One child experienced a late moderate eczematous allergic reaction in the optional follow‐up period, indicating the need for close monitoring of subjects starting new formula. Weight and length gain followed the World Health Organization growth curves. Changes in frequency and consistency of stools upon test formula intake were transient.ConclusionsThe newly developed eHWF is a suitable option in CMA treatment as all subjects tolerated the product. This result is in line with the international criteria for hypoallergenicity (American Academy of Pediatrics) that state that more than 90% of CMA children must tolerate the formula. Use of the formula is also associated with normal growth curves and GI tolerability.Trial registrationTrial NL3889, https://www.trialregister.nl/trial/3889.

Transient low IgG4 levels cause recurrent wheezing requiring multiple hospitalizations in infancy.

To investigate whether the immunoglobulin G (IgG4) subclass is associated with recurrent wheezing and/or asthma in infants. From April 2015 to March 2016, 77 infants under 3 years old who attended our hospital were enrolled in four groups (Group 1, controls; Group 2, infants with recurrent wheezing and multiple hospitalizations despite starting inhaled corticosteroids [ICS]; Group 3, infants with recurrent wheezing and without hospitalization after starting ICS; Group 4, allergic infants without wheezing). The relationship between IgG subclasses, especially IgG4, and recurrent wheezing resistant to ICS and requiring multiple hospitalizations in infants was examined. The serum IgG, IgM, IgA, IgG1, IgG2, and IgG3 levels did not differ significantly among the four groups. The IgG4 level in Group 2 infants (3.1 ± 0.2 mg/dl) was significantly lower than in Groups 1,3, and 4 (9.9 ± 8.0, 8.4 ± 6.1, and 23.4 ± 18.0 mg/dl). Of the 16 infants in Group 2, 10 could be followed to age 6 years. Nine of them had no recurrent wheezing at 6 years without medication. In addition, their IgG4 levels at age 6 years (16.1 ± 7.1 mg/dl) were significantly increased from those in infancy (3.0 ± 0.1 mg/dl). A transient low IgG4 level in infancy might cause recurrent wheezing and/or asthmatic symptoms in infants, and it may be one of the types of early transient wheezing.

Single low-dose exposure to cow's milk at diagnosis accelerates cow's milk allergic infants' progress on a milk ladder programme.

BackgroundCow's milk protein allergy (CMPA) is one of the most common food allergies in infancy. Most infants with CMPA tolerate baked milk from diagnosis and gradually acquire increased tolerance. Nevertheless, parents often display significant anxiety about this condition and a corresponding reluctance to progress with home introduction of dairy due to concerns about possible allergic reactions.ObjectiveTo evaluate the impact on gradual home introduction of foods containing cows’ milk after a supervised, single low‐dose exposure to whole milk at time of diagnosis.MethodsInfants less than 12 months old referred with suspected IgE‐mediated cow's milk allergy were recruited to an open‐label randomized, controlled trial of intervention—a single dose of fresh cow's milk, using the validated dose of milk that would elicit reactions in 5% of CMPA subjects—the ED05 – vs routine care. Both groups implemented graded exposure to CM (using the 12 step MAP Milk Tolerance Induction Ladder), at home. Parents completed food allergy quality of life questionnaires and State and Trait Anxiety Inventories (STAI). Main outcome measures were milk ladder position at 6 months and 12 months post‐randomization.ResultsSixty patients were recruited, 57 (95%) were followed to 6 months. By 6 months, 27/37 (73%) intervention subjects had reached step 6 or above on the milk ladder compared to 10/20 (50%) control subjects (p = .048). By 6 months, 11/37 (30%) intervention subjects had reached step 12 (i.e. drinking unheated cow's milk) compared to 2/20 (10%) of the controls (p = .049). Twelve months post‐randomization, 31/36(86%) of the intervention group and 15/19(79%) of the control group were on step 6 or above. However, 24/37 (65%) of the intervention group were at step 12 compared to 7/20 (35%) of the control group (p = .03). Maternal STAIs were significantly associated with their infants’ progress on the milk ladder and with changes in skin prick test and spIgE levels at 6 and 12 months.ConclusionThis study demonstrates the safety and effectiveness of introduction of baked milk implemented immediately after diagnosis of cows’ milk allergy in a very young cohort. A supervised single dose of milk at the ED05 significantly accelerates this further, probably by giving parents the confidence to proceed. Maternal anxiety generally reflects infants’ progress towards completion of the milk ladder, but pre‐existing high levels of maternal anxiety are associated with poorer progress.

P102 CHARACTERIZATION OF ALLERGIC INFANTS WHO FAIL INITIAL PEANUT ORAL FOOD CHALLENGES, IS THERE A PATTERN?

High-risk allergic infants (HRAI) undergo peanut oral food challenges (POFC) for peanut tolerization. NIAID has suggested protocols for POFC in HRAI. Characterization of failed POFC is important for practicing Allergists.

Mother's Milk Microbiome Shaping Fecal and Skin Microbiota in Infants with Food Allergy and Atopic Dermatitis: A Pilot Analysis.

The child microbiome, including gut and skin communities, is shaped by a multitude of factors, and breastfeeding is one of the most essential. Food allergy (FA) and atopic dermatitis (AD) are among the most common diseases in pediatrics, with the prevalence of each up to 6% and 20%, respectively. Therefore, we aimed at finding differences between the fecal and skin microbiomes of FA and AD patients in the context of breastfeeding, by means of the Illumina sequencing of 16S rRNA gene fragment libraries amplified from the total DNA isolated from samples collected from allergic and healthy infants. We also analyzed milk samples from the mothers of the examined children and searched for patterns of incidence suggesting milk influence on an infant’s allergy status. Here we show that a mother’s milk influences her child’s fecal and skin microbiomes and identify Acinetobacter as the taxon whose abundance is correlated with milk and child-derived samples. We demonstrate that breastfeeding makes allergic children's fecal and skin communities more similar to those of healthy infants than in the case of formula-feeding. We also identify signature taxa that might be important in maintaining health or allergy development.

Tolerance development in cow’s milk–allergic infants receiving amino acid–based formula: A randomized controlled trial

Tolerance development is an important clinical outcome for infants with cow's milk allergy. This multicenter, prospective, randomized, double-blind, controlled clinical study (NTR3725) evaluated tolerance development to cow's milk (CM) and safety of an amino acid-based formula (AAF) including synbiotics (AAF-S) comprising prebiotic oligosaccharides (oligofructose, inulin) and probiotic Bifidobacterium breve M-16V in infants with confirmed IgE-mediated CM allergy. Subjects aged ≤13 months with IgE-mediated CM allergy were randomized to receive AAF-S (n= 80) or AAF (n= 89) for 12 months. Stratification was based on CM skin prick test wheal size and study site. After 12 and 24 months, CM tolerance was evaluated by double-blind, placebo-controlled food challenge. Alogistic regression model used the all-subjects randomized data set. At baseline, mean± SD age was 9.36± 2.53 months. At 12 and 24 months, respectively, 49% and 62% of subjects were CM tolerant (AAF-S 45% and 64%; AAF 52% and 59%), and not differ significantly between groups. During the 12-month intervention, the number of subjects reporting at least 1 adverse event did not significantly differ between groups; however, fewer subjects required hospitalization due to serious adverse events categorized as infections in the AAF-S versus AAF group (9% vs 20%; P= .036). After 12 and 24 months, CM tolerance was not different between groups and was in line with natural outgrowth. Results suggest that during the intervention, fewer subjects receiving AAF-S required hospitalization due to infections.

A Combined Analysis of Gut and Skin Microbiota in Infants with Food Allergy and Atopic Dermatitis: A Pilot Study.

The gut microbiota in patients with food allergy, and the skin microbiota in atopic dermatitis patients differ from those of healthy people. We hypothesize that relationships may exist between gut and skin microbiota in patients with allergies. The aim of this study was to determine the possible relationship between gut and skin microbiota in patients with allergies, hence simultaneous analysis of the two compartments of microbiota was performed in infants with and without allergic symptoms. Fifty-nine infants with food allergy and/or atopic dermatitis and 28 healthy children were enrolled in the study. The skin and gut microbiota were evaluated using 16S rRNA gene amplicon sequencing. No significant differences in the α-diversity of dermal or fecal microbiota were observed between allergic and non-allergic infants; however, a significant relationship was found between bacterial community structure and allergy phenotypes, especially in the fecal samples. Certain clinical conditions were associated with characteristic bacterial taxa in the skin and gut microbiota. Positive correlations were found between skin and fecal samples in the abundance of Gemella among allergic infants, and Lactobacillus and Bacteroides among healthy infants. Although infants with allergies and healthy infants demonstrate microbiota with similar α-diversity, some differences in β-diversity and bacterial species abundance can be seen, which may depend on the phenotype of the allergy. For some organisms, their abundance in skin and feces samples may be correlated, and these correlations might serve as indicators of the host’s allergic state.

Partially Hydrolyzed Whey Protein: A Review of Current Evidence, Implementation, and Further Directions

Background: Human milk is known to be the best nutrition for infants as it provides many health benefits. For non-breastfed infants, cow's milk based infant formula is the most optimal option to provide the needed nutrition. However, approximately 2-5% of all formula-fed infants experience cow’s milk allergy during their first year of life. Partially hydrolyzed whey formula (pHF-W) have been widely recommended to prevent the development of allergic disease in infants. However, according to epidemiological data, approximately half of the infants developing allergy are not part of the at-risk group.Objectives and Methods: This article aims to review the effects of pHF-W in preventing allergy, especially atopic disease, in all non-breastfed infants, as well as the safety aspect of pHF-W if used as routine formula. The role of pHF-W in the management of functional gastro-intestinal (GI) disorders is also reviewed.Results: Several clinical studies showed that pHF-W decrease the number of infants with eczema. The strongest evidence is provided by the 15-year follow up of the German Infant Nutritional Intervention study which showed reduction in the cumulative incidence of eczema and allergic rhinitis in pHF-W (OR 0.75, 95% CI 0.59-0.96 for eczema; OR 0.67, 95% CI 0.47-0.95 for allergic rhinitis) and casein extensively hydrolysed formula group (OR 0.60, 95% CI 0.46-0.77 for eczema; OR 0.59, 95% CI 0.41-0.84 for allergic rhinitis), compared to CMF as a control, after 15 years of follow-up. pHF-W was also found to be beneficial in the management of functional GI disorders such as regurgitation, constipation and colic.Conclusions: The use of pHF-W in allergic infants has been recommended in various guidelines across the countries, as a primary prevention of allergic disease. One pHF-W has been approved by the US FDA and the European Commission's European Food Safety Authority (EFSA) for its safety and suitability as a routine infant formula for all healthy infants. According to the data obtained in the management of functional GI disorders, pHF-W is better tolerated than formula with intact protein. Further studies assessing the effect of routine use of pHF-W in a larger population of non-breastfed infants should also be conducted, in order to observe any potential harm and to determine the benefit and cost-effectiveness ratio.

Gut Microbiota Profile in Children with IgE-Mediated Cow's Milk Allergy and Cow's Milk Sensitization and Probiotic Intestinal Persistence Evaluation.

Food allergy (FA) and, in particular, IgE-mediated cow’s milk allergy is associated with compositional and functional changes of gut microbiota. In this study, we compared the gut microbiota of cow’s milk allergic (CMA) infants with that of cow’s milk sensitized (CMS) infants and Healthy controls. The effect of the intake of a mixture of Bifidobacterium longum subsp. longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63 on gut microbiota modulation of CMA infants and probiotic persistence was also investigated. Gut microbiota of CMA infants resulted to be characterized by a dysbiotic status with a prevalence of some bacteria as Haemophilus, Klebsiella, Prevotella, Actinobacillus and Streptococcus. Among the three strains administered, B. longum subsp. infantis colonized the gastrointestinal tract and persisted in the gut microbiota of infants with CMA for 60 days. This colonization was associated with perturbations of the gut microbiota, specifically with the increase of Akkermansia and Ruminococcus. Multi-strain probiotic formulations can be studied for their persistence in the intestine by monitoring specific bacterial probes persistence and exploiting microbiota profiling modulation before the evaluation of their therapeutic effects.