Reduced gut microbial diversity in early life is associated with later development of eczema but not atopy in high-risk infants.

BACKGROUND: Alterations in intestinal microflora have been linked to the development of allergic disease. Recent studies suggest that healthy infant immune development may depend on the establishment of a diverse gut microbiota rather than the presence or absence of specific microbial strains. OBJECTIVES: We investigated the relationship between diversity of gut microbiota in the early postnatal period and subsequent development of eczema and atopy in the first year of life. METHODS: Fecal samples were collected 1 wk after birth from 98 infants at high risk of allergic disease, who were followed prospectively to age 12 months. Fecal microbial diversity was assessed by terminal restriction fragment length polymorphism (T-RFLP) using restriction enzymes Sau96I and AluI, with a greater number of peaks representing greater diversity of bacterial communities. RESULTS: Microbial diversity at day 7 was significantly lower in infants with eczema at age 12 months as compared to infants without eczema (AluI mean number of peaks 13.1 vs. 15.5, p = 0.003, 95% CI for difference in means -3.9, -0.8; Sau96I 14.7 vs. 17.2, p = 0.03, 95% CI -4.9, -0.3). No differences were observed for atopic compared to non-atopic infants, or infants with two allergic parents compared to those with one or no allergic parent. CONCLUSIONS: A more diverse intestinal microbiota in the first week of life is associated with a reduced risk of subsequent eczema in infants at increased risk of allergic disease. Interventions that enhance microbial diversity in early life may provide an effective means for the prevention of eczema in high-risk infants.

Adherence to recommendations for primary prevention of atopic disease in neonatology clinical practice.

The prevalence and severity of atopic manifestations in children are increasing in western countries in the last decades. Specific nutritional intervention may prevent or delay the onset of atopic diseases in infants at high risk of developing allergy. These nutritional interventions should be applied early in the perinatal period to have a chance of success. Thus, we assessed adherence to the dietary management recommendations of the Committee on Nutrition and Section on Allergy and Immunology of the American Academy of Pediatrics (AAP) for the prevention of atopic diseases in neonatal age through an audit study. Questionnaire was administered to the chiefs of 30 maternity units (MU) with more than 1500 live births/yr to report the policy applied in their MU. Twenty-two MU returned the questionnaire. Identification of high-risk newborns was routinely performed only in 7/22 MU (31.8%). High-risk newborns were identified by the presence of at least two or one first-degree relative (parent or sibling) with documented allergic disease by 18.2% and 45.5% of MU, respectively. Specific maternal dietary restrictions during lactation were adopted in 7/22 MU (31.8%). Extensively or partially hydrolyzed formula was prescribed for bottle-fed high-risk infants in 22.7% of MU. Only 2/22 MU have a policy in complete agreement with the nutritional intervention proposed by the AAP. Our study suggest a poor adherence to dietary recommendations for primary prevention of atopic disease in neonatology clinical practice. Further efforts should be planned to improve the knowledge and the application of these preventive strategies.

[Component-based diagnostic approach. Detection of sensitization to lipid transfer proteins in food allergy]. / Komponentenbasierte Diagnostik. Nachweis einer Soforttypsensibilisierung gegen Lipid-Transfer-Proteine bei Nahrungsmittelallergie

Sensitization to lipid transfer proteins (LTPs), a pan-allergen in plants, causes severe anaphylactic reactions to foods, especially in the Mediterranean area. A component-based diagnostic approach identified the peach LTP Pru p 3 as a major allergen. We present the case of a 30-year-old LTP-sensitized Spanish woman with a history of severe anaphylactic reaction to grapes, apple and cauliflower in which the detection of specific IgE against the recombinant protein Pru p 3 led to the diagnosis.

The Effects of Early Nutritional Interventions on the Development of Atopic Disease in Infants and Children: The Role of Maternal Dietary Restriction, Breastfeeding, Hydrolyzed Formulas, and Timing of Introduction of Allergenic Complementary Foods.

This clinical report updates and replaces a 2008 clinical report from the American Academy of Pediatrics, which addressed the roles of maternal and early infant diet on the prevention of atopic disease, including atopic dermatitis, asthma, and food allergy. As with the previous report, the available data still limit the ability to draw firm conclusions about various aspects of atopy prevention through early dietary interventions. Current evidence does not support a role for maternal dietary restrictions during pregnancy or lactation. Although there is evidence that exclusive breastfeeding for 3 to 4 months decreases the incidence of eczema in the first 2 years of life, there are no short- or long-term advantages for exclusive breastfeeding beyond 3 to 4 months for prevention of atopic disease. The evidence now suggests that any duration of breastfeeding ≥3 to 4 months is protective against wheezing in the first 2 years of life, and some evidence suggests that longer duration of any breastfeeding protects against asthma even after 5 years of age. No conclusions can be made about the role of breastfeeding in either preventing or delaying the onset of specific food allergies. There is a lack of evidence that partially or extensively hydrolyzed formula prevents atopic disease. There is no evidence that delaying the introduction of allergenic foods, including peanuts, eggs, and fish, beyond 4 to 6 months prevents atopic disease. There is now evidence that early introduction of peanuts may prevent peanut allergy.

Impact of maternal atopy and probiotic supplementation during pregnancy on infant sensitization: a double-blind placebo-controlled study.

BACKGROUND: The effects of breastfeeding and probiotics on infant sensitization still remain discrepant. OBJECTIVE: To explore probable explanatory factors in infant sensitization and the protective effect of probiotics. METHODS: Altogether 171 mother-infant pairs from an ongoing placebo-controlled double-blind study with nutrition modulation by dietary counselling and probiotic supplementation were studied. Skin prick testing was done in infants at 6 and 12 months and in mothers at third trimester of pregnancy. The breast milk concentrations of cytokines TGF-beta2, soluble CD14, IFN-gamma, TNF-alpha, IL-10, IL-6, IL-4 and IL-2 were measured. RESULTS: The risk of sensitization increased in infants with allergic mothers breastfeeding over 6 months [odds ratio (OR=4.83, P=0.005)], or exclusively breastfeeding over 2.5 months (OR=3.4, P=0.018). Probiotic supplementation had a protective effect against sensitization in infants with a high hereditary risk due to maternal sensitization (OR=0.3, P=0.023). The concentration of TGF-beta2 tended to be higher in the colostrum of the mothers in the probiotic group as compared with those on placebo (probiotic/placebo ratio=1.50, P=0.073). A similar result was obtained in the subgroup of allergic mothers (probiotic/placebo ratio=1.56, P=0.094). CONCLUSION: Infants of atopic mothers, specifically when breastfed exclusively over 2.5 months or totally over 6 months, had a higher risk of sensitization at the age of 12 months. This risk could be reduced by the use of probiotics during pregnancy and lactation, partly by resulting in a beneficial composition of the breast milk.

Probiotics for atopic diseases.

One suggestion for why some people develop atopic diseases, such as allergic rhinitis, asthma and atopic eczema, is that there are alterations in their intestinal microflora not seen in those without such conditions. This idea underlies the proposal that probiotics (orally administered micro-organisms) containing, for example, Lactobacillus and Bifidobacterium species, might help to prevent and treat atopic disorders by altering intestinal microflora. We have recently reviewed the use of probiotics for gastrointestinal disorders. Here, we look at whether they have a place in the prevention and treatment of atopic diseases.

A double-blind comparison of olive oil and a combination of evening primrose oil and fish oil in the management of canine atopy.

A randomised double-blind parallel study lasting eight weeks was used to assess the effects of olive oil in a group of atopic dogs whose clinical signs were well controlled by dietary supplementation with a combination of evening primrose oil and fish oil. Nine of the 11 dogs which continued to receive this combination were considered unchanged at the conclusion of the study, whereas eight of the 10 dogs switched to olive oil had deteriorated. The mean plasma concentration of dihomogammalinolenic acid, a precursor of potentially antiinflammatory mediators, was significantly reduced (P < 0.05) in the olive oil-treated group at the end of the study. There were no significant differences between the mean plasma linoleic, eicosapentaenoic and arachidonic acid concentrations in the two groups. These findings suggest that olive oil is not an effective therapeutic agent in the control of canine atopy.

[Potential dietary interventions for prevention and treatment of infant allergy]. / Potenciales intervenciones alimentarias en el manejo y prevención de la alergia en lactantes.

The incidence of atopic diseases such as asthma, atopic dermatitis and food allergies has increased exponentially in recent decades. Although atopic diseases have a clear genetic basis, environmental factors such as the diet, seems to play an important role in its development. This article summarizes main studies exploring whether feeding practices of mothers and infants intervenes in the development of allergic diseases. The potential role of dietary practices of the mother and infants for the prevention and/or management of allergies in infants is discussed. The available evidence was analyzed for: (1) does mothers consumption of essential fatty acids, prebiotics and probiotics modulates the onset of allergic disorders?, (2) Does breastfeeding and artificial formula prevent/trigger the onset of allergy symptoms? (3) Does timing of introduction of solid feeding and the selection of certain common food allergens participate in achieving oral tolerance in infants? Accumulated evidence in recent years suggest that exposure to allergens early in life may promote immune tolerance and contribute to prevent infant food sensitization.

Durante las últimas décadas la incidencia de enfermedades atópicas como el asma, dermatitis atópica y alergias a alimentos ha aumentado de manera exponencial. Aunque las enfermedades atópicas tienen una clara base genética, los factores ambientales, principalmente la dieta, pueden tener una influencia importante en su desarrollo. Este artículo resume los principales estudios que investigan hasta qué punto las prácticas alimentarias de la madre y los lactantes intervienen en la aparición de enfermedades alérgicas, discutiendo su posible rol en la prevención y/o manejo de alergias en lactantes con y sin historia familiar de alergia. La evidencia existente se evaluó en relación a: 1) si el consumo de ácidos grasos esenciales y de pre y probióticos por parte de la madre durante el período de gestación o la lactancia, modularían la aparición de desórdenes alérgicos, 2) si la alimentación del lactante, alimentado con lactancia materna/fórmulas artificiales podría prevenir/gatillar la aparición de síntomas, y 3) si la edad de introducción de la alimentación complementaria y hacerlo con determinados alérgenos alimentarios podría influir en alcanzar la tolerancia oral del lactante. La evidencia acumulada en las últimas décadas sugiere que, contra la postura histórica en el tema, la exposición a alérgenos en etapas tempranas de la vida podría promover la tolerancia del sistema inmune del lactante y prevenir la sensibilización a alimentos.

Preventive effects of C-2 epimeric isomers of tea catechins on mouse type I allergy.

The preventive effects of C-2 epimeric isomers of (-)-epigallocatechin-3-O-gallate (EGCG) and the O-methylated derivative, (-)-epigallocatechin-3-O-(3-O-methyl)gallate (EGCG3''Me), against ovalbumin-induced type I allergy in male mice were investigated. EGCG and EGCG3''Me exhibited strong antiallergic effects by oral administration at doses of 25 and 50 mg/kg body weight. The antiallergic effects of their C-2 epimers, (-)-gallocatechin-3-O-gallate and (-)-gallocatechin-3-O-(3-O-methyl)gallate (GCG3''Me), on mouse type I allergy were almost equivalent to and/or as strong as those of the corresponding original catechins, respectively. Oral administration of these compounds at a dose of 50 mg/kg body weight tended to suppress the increases in interleukin-4 levels in the abdominal walls of allergic mice and immunoglobulin E levels in the serum of allergic mice. In particular, the administration of GCG3''Me exhibited significant effects on the production and/or release of these parameters stimulating type 2 T helper cells and mast cells in the type I allergic process. These results indicated that C-2 epimerization of tea catechins, which are produced during heat processing at high temperatures, would not be disadvantageous for preventive effects on type I allergy.

The concept of hypoallergenicity for atopy prevention.

Infancy represents the period in which an individual may be at the highest risk of sensitization. During the first year of life around 2.5% of neonates experience hypersensitivity reactions to cow's milk protein, which is highly associated with early exposure to cow's milk. Attempts to avoid sensitization in this very early period of life and to prevent allergic diseases focus on diets with reduced allergenicity and possibly on the induction of oral tolerance. Hydrolyzed infant formulas are characterized by a reduced allergenicity and thus recommended as substitute or supplementary to breastfeeding during the first 4-6 months of life for infants at high risk of developing atopic diseases. This concept of hypoallergenicity has been shown effective in clinical studies. Both partially and extensively hydrolyzed formulas have demonstrated a potential in protecting from allergic diseases, mainly atopic eczema and food allergy. The in vitro characterization of allergenicity by the degree of hydrolyzation and peptide size, however, does not necessarily predict the immunogenic effect in humans, as it could be shown that the preventive effect seems to be dependent on the process rather than on the degree of hydrolyzation, which could be best explained by a possible production of tolerogenic epitopes.

Omega-3 and omega-6 fatty acid exposure from early life does not affect atopy and asthma at age 5 years.

BACKGROUND: The Childhood Asthma Prevention Study was a randomized controlled trial conducted in children with a family history of asthma in whom omega-3 fatty acid supplementation and restriction of dietary omega-6 fatty acids did not prevent asthma, eczema, or atopy at age 5 years. OBJECTIVE: We sought to examine the relation of all measures of omega-3 and omega-6 polyunsaturated fatty acids with outcomes at age 5 years in the whole birth cohort, regardless of randomization group. METHODS: Plasma fatty acids were measured at 18 months, 3 years, and 5 years. Compliance with the fatty acid supplements was estimated every 6 months. Dietary intake was assessed at 18 months by means of weighed-food record and at 3 years by means of food-frequency questionnaire. At age 5 years, 516 children were examined for wheeze and eczema (questionnaire) and atopy (skin prick tests, n = 488). Multiple logistic regression was used to evaluate associations between exposures and outcomes. RESULTS: Plasma levels of omega-3 or omega-6 fatty acids were not associated with wheeze, eczema, or atopy at age 5 years (P = .11-.96). Overall, fatty acid exposure, measured as plasma levels, dietary intake, and compliance with supplements, was not associated with any respiratory or allergic outcomes (P = .35-.59). CONCLUSION: This observational analysis of the cohort, using the full range of observed variation in omega-3 and omega-6 fatty acid exposure, supports the negative findings of the randomized controlled trial. CLINICAL IMPLICATIONS: Modification of dietary polyunsaturated fatty acids in early childhood is not helpful in preventing atopy and asthma.

Dietary prevention of allergic disease in children: are current recommendations really based on good evidence?

We provide a critical appraisal of the literature on the effects of dietary prevention of atopic disease in children. In our view, currently available studies suffer from lack of blinding which is a major problem if the primary end point is subjective (such as the diagnosis of eczema). In addition, long-term follow-up suggests that atopic symptoms are delayed rather than truly prevented, and that only the mildest cases are prevented (or delayed). Although it has been reported that cow's milk allergy is truly prevented by dietary interventions in early life, this has never been demonstrated by double-blind placebo-controlled food challenges. No studies to date have shown effects of hypoallergenic formulae on objective markers of atopic sensitization, such as specific IgE levels. Finally, there is no universally accepted pathophysiological mechanism which could explain the usefulness of hypoallergenic formulae in allergy prevention. In conclusion, we feel that the currently available evidence on the allergy preventive effects of hypoallergenic formulae is insufficient to justify blanket advice being given to 'high risk' families. Such advice gives parents the hope that they can actually prevent allergy in their children which may not be justified. A cautious approach in advising interventions with hypoallergenic formulae to prevent allergy in high-risk infants is warranted.

Probiotics: on-going research on atopic individuals.

The challenge for the modern health care system is to fight against the increasing prevalence of atopic disease. The introduction of scientifically composed probiotic functional foods for prophylactic or therapeutic purposes could be one solution. Probiotics are live microbial food supplements or components of bacteria which have beneficial effects on human health. Specific strains have been demonstrated to exert powerful anti-pathogenic, anti-inflammatory and anti-allergic effects. The hygiene hypothesis suggests that atopic disease may arise from a lack of counterbalancing microbial exposure at an early age. The initial compositional development of the gut microflora is considered a key determinant of the development of both the immune responder phenotype and normal gut barrier functions. The regulatory role of probiotics in human allergic disease was first emphasised in the demonstration of a suppressive effect on lymphocyte proliferation and interleukin-4 generation in vitro. Subsequently, a significant improvement in the clinical course of atopic eczema was reported in infants given a probiotic-supplemented diet. The potential of probiotics to reduce the risk of atopic disease has recently been demonstrated in a double-blind, placebo-controlled study: probiotics administered pre- and postnatally for 6 months to at-risk subjects reduced the prevalence of atopic eczema to half of that observed in infants receiving placebo. Ongoing research is directed towards the development of novel techniques to characterise the gut microflora. Future research will clarify the mechanisms to control specific physiological processes in the evolution of atopic disease in at-risk populations or in the management of allergic diseases.

[Influence of diet during pregnancy and the coexistence of allergy during the 1st year of life]. / Influencia de la dieta durante el embarazo y la coexistencia de alergia en el primer año de vida.

Thirty atopic pregnant women by clinical history, skin testing, and laboratory data, and 10 non-atopic women, were studied for the influence of a diet on the outcome of their babies. The atopic women were divided into two groups: non-diet and diet group, the last group, decided to follow a non-allergenic diet that they started after 11 weeks of pregnancy. We had a follow up of the babies from all pregnancies after birth for a year. As a part of the babies clinical history, we determined the IgE concentration within 2 months after birth. Our data indicated that two babies from diet group and non from the control group, had an atopic disease during the first year of life, in contrast, five babies from the non-diet group, these preliminary results, suggested that a non-allergenic diet in atopic pregnant women, may decrease the morbidity of atopic disease during the first year of life.

Compliance with a dietary manipulation programme in families with infants prone to atopy.

The success of familial compliance with a dietary manipulation programme was studied prospectively in 91 newborn babies from atopic families for up to 12 months. The control group consisted of 72 infants from non-atopic families. The percentages of infants breast-fed at the age of six months were 58% and 38% in the study group and control group, respectively. The introduction of cow's milk based formulas was postponed until the age of three months in 63% of the infants in the study group and 47% of the infants in the control group. Solid food was avoided during the first three months in 76% and 45% of the infants in the study group and control group, respectively. Maternal age, smoking and low social class were associated with poor compliance. The existence of atopic dermatitis in any member of the family was associated with good compliance. The main advantages of our programme were the increased number of children breast-fed until the age of six months, and the reduced number of infants introduced to cow's milk based formulas or solid food before three months of age.

Possible consequences of elimination diets in asymptomatic immediate hypersensitivity to fish.

The natural history of IgE antibodies to food without related symptoms is unknown. We have followed the progress of 7 children with various atopic diseases and asymptomatic immediate hypersensitivity to fish, treated with elimination diet in spite of full alimentary tolerance. During the diet period, between 24 and 113 months, all 7 patients presented immediate symptoms upon accidental exposure to or challenge tests with fish (skin symptoms in all 7 cases, digestive in 5, respiratory in 4, and anaphylaxis in 2), which differed from those related to atopic diseases previously present. The levels of fish-specific IgE (prick test, RAST) remained unchanged or were increased. These findings suggest that during elimination diet, and perhaps due to minimal and hidden contact with the allergen, the patients' degree of sensitization may increase, turning an asymptomatic into a symptomatic immediate hypersensitivity.

Development of atopic disease in babies whose mothers were receiving exclusion diet during pregnancy--a randomized study.

In a prospective, randomized study, we have monitored the effect of maternal abstention from cow's milk and egg on the development of atopy in babies. Two hundred twelve women were followed from midpregnancy. We report the occurrences of allergies in their babies up to 18 months of age, as assessed by skin prick testing, determination of serum IgE, questionnaires, and blinded physical examination by a pediatric allergist. Whatever the method that was used, there was no statistically significant difference between babies whose mothers received the "diet" or the "nondiet." Other factors known to influence the risk of atopy like heredity, sex, month of birth, breast-feeding, and exposure to tobacco smoke, animal dandruff, and solid food did not differ between the groups. The mothers receiving the exclusion diet, by their own choice, had diminished their intake of milk and egg during lactation also, and therefore, their babies were significantly less exposed to cow's milk before 6 months. Still, atopy was equally abundant among their children. Thus, maternal elimination diet during late pregnancy did not protect the baby against allergy.

Influence of dietary manipulation on incidence of atopic disease in infants at risk.

Of 5,500 newborn infants whose family histories were screened, 900 were found to have anamnestic risk. Cord-blood IgE was evaluable in 4,677 of these newborns, of which 394 had levels > or = 1 IU/mL; 84 infants had both anamnestic risk and elevated cord-blood IgE levels. Parents of infants with anamnestic risk were informed of their child's risk of atopy. Additionally, for 391 infants at two of the three participating hospitals, a preventive diet was prescribed that recommended breastfeeding for the first 6 months of life, with maternal diet restricted to no more than 200 dL of cow milk per day, no more than one egg per week, and no tomato, fish, shellfish, nuts, or foods allergenic to the mother. Only soy formula was recommended, and introduction of solid foods was also carefully prescribed. Furthermore, doctors recommended against exposure to tobacco smoke, animal allergens, and early entrance into daycare. Evaluable infants whose parents complied with the prescribed diet were found to have a lower incidence of atopy during the first year of life (13.3%, n = 158) than infants whose parents had ignored the prescribed diet (54.7%, n = 86) or infants whose parents were offered no dietary recommendations (28.9%, n = 218). Differences between the compliant group and the two groups with unrestricted diets were significant, indicating that this prescribed diet may protect against or delay onset of food allergies during the first year of life.

Definitions and diagnosis of food intolerance and food allergy: consensus and controversy.

This article describes the terms used for the various syndromes and diseases associated with reactions to foods; it outlines the principal types of food intolerance encountered in children, with particular emphasis on those caused by immune-mediated reactions of immediate hypersensitivity. Terms defined include food intolerance or food sensitivity; food allergy or food hypersensitivity; psychologically based food reactions (food aversions); and psychosocial and neurologic dysfunction. The spectrum of food sensitivity is considerable, and diagnosis is generally based on the monitoring of effects of exclusion diets and provocation tests, after appropriate objective measures are first selected. In children, manifestations of IgE-mediated food allergy (often in association with other immune mechanisms) include self-limiting and immediate reactions (e.g., urticaria, wheeze) and chronic diseases (food-sensitive enteropathies, eczema). Controversial and unresolved issues exist with some other conditions, including eosinophilic gastroenteritis, occult gastrointestinal bleeding, protein-losing enteropathy, and attention deficit disorder with hyperactivity. New methods for clinical investigation of gastrointestinal tract function and intestinal immune reactions are required to assess the relevance of foods in these conditions.