Immunomodulatory diet in pediatric age.

In the last few decades, the importance of a functioning immune system and health status has become more evident. Multiple factors are able to influence the development of chronic diseases and diet is one of the most important environmental factors. Evidence demonstrates that dietary patterns high in fat and low in fiber are associated with the development of non-communicable diseases. Moreover, optimal nutritional status can modulate immune maturation and response to inflammation. During inflammatory conditions, nutritional deficiencies may occur, establishing a vicious circle, consequently a balanced nutritional status is essential to prevent and counteract infections. Dietary diversity can prevent allergic diseases and nutrients such as DHA, arginine, vitamins and trace elements have an impact on physical barriers (such as gut mucosal barrier and skin), on the immune system response and on microbiome modulation. Protein deficiencies can compromise innate and adaptive immune functions; arginine availability can affect the immune response in injured states and other disease processes; EPA and DHA can modulate both innate and adaptive immunity; prebiotics have a beneficial effect on the functioning of the immune system. Zinc, copper, selenium and iron are involved in the correct development and function of the immune system. Vitamins D, E, A, B and C have a role on immune system through different mechanisms of action. Since a complex interplay exists between diet, microbiome and epigenetic factors which determine nutrient-induced changes on the immune function, the effect of each single nutrient may be difficult to study. Well-designed intervention studies, investigating the effects of whole dietary pattern, should be performed to clarify impact of foods on the immune function and disease risk.

Impact of Early Life Nutrition on Children's Immune System and Noncommunicable Diseases Through Its Effects on the Bacterial Microbiome, Virome and Mycobiome.

The first 1000 days of life, including the intrauterine period, are regarded as a fundamental stepping stone for the development of a human. Unequivocally, nutrition during this period plays a key role on the proper development of a child, both directly through the intake of essential nutrients and indirectly by affecting the composition of the gut microbiota. The gut microbiota, including bacteria, viruses, fungi, protists and other microorganisms, is a highly modifiable and adaptive system that is influenced by diet, lifestyle, medicinal products and the environment. Reversely, it affects the immune system in multiple complex ways. Many noncommunicable diseases (NCDs) associated with dysbiosis are "programmed" during childhood. Nutrition is a potent determinant of the children's microbiota composition and maturation and, therefore, a strong determinant of the NCDs' programming. In this review we explore the interplay between nutrition during the first 1000 days of life, the gut microbiota, virome and mycobiome composition and the development of NCDs.

Vitamin D and Immunity in Infants and Children.

The last couple of decades have seen an explosion in our interest and understanding of the role of vitamin D in the regulation of immunity. At the molecular level, the hormonal form of vitamin D signals through the nuclear vitamin D receptor (VDR), a ligand-regulated transcription factor. The VDR and vitamin D metabolic enzymes are expressed throughout the innate and adaptive arms of the immune system. The advent of genome-wide approaches to gene expression profiling have led to the identification of numerous VDR-regulated genes implicated in the regulation of innate and adaptive immunity. The molecular data infer that vitamin D signaling should boost innate immunity against pathogens of bacterial or viral origin. Vitamin D signaling also suppresses inflammatory immune responses that underlie autoimmunity and regulate allergic responses. These findings have been bolstered by clinical studies linking vitamin D deficiency to increased rates of infections, autoimmunity, and allergies. Our goals here are to provide an overview of the molecular basis for immune system regulation and to survey the clinical data from pediatric populations, using randomized placebo-controlled trials and meta-analyses where possible, linking vitamin D deficiency to increased rates of infections, autoimmune conditions, and allergies, and addressing the impact of supplementation on these conditions.

Atopic dermatitis and its relation to food allergy.

PURPOSE OF REVIEW: To present the most recent evidence on atopic dermatitis and its relation to food allergy. RECENT FINDINGS: Atopic dermatitis is a chronic inflammatory disorder of the skin characterized by impaired skin barrier because of multifactorial causes including genetic factors, immune dysregulation, and skin microbiome dysbiosis. Infants with temporary skin barrier disruption and/or persistent atopic dermatitis are particularly at risk of developing food allergy (during the so-called atopic march), with up to half of patients demonstrating positive food-specific IgE and one-third of severe cases of atopic dermatitis having positive symptoms on oral food challenge. A high proportion of children with atopic dermatitis exhibit asymptomatic sensitization to foods, and skin testing to identify potential food triggers is not recommended unless the patient has a history suggestive of food allergy and/or moderate-to-severe atopic dermatitis unresponsive to optimal topical care. Indeed, indiscriminate testing can lead to a high proportion of false-positive tests and harmful dietary evictions. Promising strategies to prevent food allergy in children with atopic dermatitis include early skincare with emollients and treatment with topical steroid, and early introduction of highly allergenic foods. SUMMARY: Further studies are required to identify risk factors for atopic dermatitis to help prevent the development of food allergy in this high-risk population.

Interventions for increasing fruit and vegetable consumption in children aged five years and under.

BACKGROUND: Insufficient consumption of fruits and vegetables in childhood increases the risk of future non-communicable diseases, including cardiovascular disease. Interventions to increase consumption of fruit and vegetables, such as those focused on specific child-feeding strategies and parent nutrition education interventions in early childhood may therefore be an effective strategy in reducing this disease burden. OBJECTIVES: To assess the effectiveness, cost effectiveness and associated adverse events of interventions designed to increase the consumption of fruit, vegetables or both amongst children aged five years and under. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and two clinical trials registries to identify eligible trials on 25 August 2019. We searched Proquest Dissertations and Theses in May 2019. We reviewed reference lists of included trials and handsearched three international nutrition journals. We contacted authors of included trials to identify further potentially relevant trials. SELECTION CRITERIA: We included randomised controlled trials, including cluster-randomised controlled trials and cross-over trials, of any intervention primarily targeting consumption of fruit, vegetables or both among children aged five years and under, and incorporating a dietary or biochemical assessment of fruit or vegetable consumption. Two review authors independently screened titles and abstracts of identified papers; a third review author resolved disagreements. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risks of bias of included trials; a third review author resolved disagreements. Due to unexplained heterogeneity, we used random-effects models in meta-analyses for the primary review outcomes where we identified sufficient trials. We calculated standardised mean differences (SMDs) to account for the heterogeneity of fruit and vegetable consumption measures. We conducted assessments of risks of bias and evaluated the quality of evidence (GRADE approach) using Cochrane procedures. MAIN RESULTS: We included 78 trials with 214 trial arms and 13,746 participants. Forty-eight trials examined the impact of child-feeding practices (e.g. repeated food exposure) in increasing child vegetable intake. Fifteen trials examined the impact of parent nutrition education in increasing child fruit and vegetable intake. Fourteen trials examined the impact of multicomponent interventions (e.g. parent nutrition education and preschool policy changes) in increasing child fruit and vegetable intake. Two trials examined the effect of a nutrition education intervention delivered to children in increasing child fruit and vegetable intake. One trial examined the impact of a child-focused mindfulness intervention in increasing vegetable intake. We judged 20 of the 78 included trials as free from high risks of bias across all domains. Performance, detection and attrition bias were the most common domains judged at high risk of bias for the remaining trials. There is very low-quality evidence that child-feeding practices versus no intervention may have a small positive effect on child vegetable consumption equivalent to an increase of 4.45 g as-desired consumption of vegetables (SMD 0.42, 95% CI 0.23 to 0.60; 18 trials, 2004 participants; mean post-intervention follow-up = 8.2 weeks). Multicomponent interventions versus no intervention has a small effect on child consumption of fruit and vegetables (SMD 0.34, 95% CI 0.10 to 0.57; 9 trials, 3022 participants; moderate-quality evidence; mean post-intervention follow-up = 5.4 weeks), equivalent to an increase of 0.36 cups of fruit and vegetables per day. It is uncertain whether there are any short-term differences in child consumption of fruit and vegetables in meta-analyses of trials examining parent nutrition education versus no intervention (SMD 0.12, 95% CI -0.03 to 0.28; 11 trials, 3078 participants; very low-quality evidence; mean post-intervention follow-up = 13.2 weeks). We were unable to pool child nutrition education interventions in meta-analysis; both trials reported a positive intervention effect on child consumption of fruit and vegetables (low-quality evidence). Very few trials reported long-term effectiveness (6 trials), cost effectiveness (1 trial) and unintended adverse consequences of interventions (2 trials), limiting their assessment. Trials reported receiving governmental or charitable funds, except for four trials reporting industry funding. AUTHORS' CONCLUSIONS: Despite identifying 78 eligible trials of various intervention approaches, the evidence for how to increase children's fruit and vegetable consumption remains limited. There was very low-quality evidence that child-feeding practice may lead to, and moderate-quality evidence that multicomponent interventions probably lead to small increases in fruit and vegetable consumption in children aged five years and younger. It is uncertain whether parent nutrition education interventions are effective in increasing fruit and vegetable consumption in children aged five years and younger. Given that the quality of the evidence is very low or low, future research will likely change estimates and conclusions. Long-term follow-up of at least 12 months is required and future research should adopt more rigorous methods to advance the field. This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Metabolite-related dietary patterns and the development of islet autoimmunity.

The role of diet in type 1 diabetes development is poorly understood. Metabolites, which reflect dietary response, may help elucidate this role. We explored metabolomics and lipidomics differences between 352 cases of islet autoimmunity (IA) and controls in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. We created dietary patterns reflecting pre-IA metabolite differences between groups and examined their association with IA. Secondary outcomes included IA cases positive for multiple autoantibodies (mAb+). The association of 853 plasma metabolites with outcomes was tested at seroconversion to IA, just prior to seroconversion, and during infancy. Key compounds in enriched metabolite sets were used to create dietary patterns reflecting metabolite composition, which were then tested for association with outcomes in the nested case-control subset and the full TEDDY cohort. Unsaturated phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, glucosylceramides, and phospholipid ethers in infancy were inversely associated with mAb+ risk, while dicarboxylic acids were associated with an increased risk. An infancy dietary pattern representing higher levels of unsaturated phosphatidylcholines and phospholipid ethers, and lower sphingomyelins was protective for mAb+ in the nested case-control study only. Characterization of this high-risk infant metabolomics profile may help shape the future of early diagnosis or prevention efforts.

Role of nutrition, infection, and the microbiota in the efficacy of oral vaccines.

Oral vaccines (OVs), provide protection against pathogens that infect mucosal surfaces and their potency relies on their capacity to elicit T- and B-cell responses directed to these surfaces. Oral vaccination efficacy has been found to vary considerably with differences in geographical locations and socioeconomic status. Specifically, in children living in resource-poor countries, undernourishment and chronic gastrointestinal (GI) infection are associated with the failure of OVs, which is a tragic outcome for the children who would benefit most from mucosal-based protection from infection. Both undernutrition and GI infection have been shown to profoundly affect the microbiota, inducing 'dysbiosis' characterized by narrowed bacterial diversity and increased frequency of bacterial clades associated with the induction of inflammation. Recent studies have demonstrated that the microbiota exerts a profound effect on the development of mucosal immune responses. Therefore, it seems likely that OV failure in resource-poor regions is affected by alterations to the immune response driven by dysbiotic changes to the microbiota. Here, we review the contribution of the microbiota to OV efficacy in the context of diet and GI infection.

Global challenges in acute diarrhea.

PURPOSE OF REVIEW: Childhood diarrhea is the most common cause of morbidity and mortality, especially in the low and middle-income countries. The burden of child mortality because of diarrhea has declined, but still a lot is desired not only to reduce diarrhea-specific mortality but reduce the overall incidence, and hence the morbidity associated with childhood diarrhea. RECENT FINDINGS: A recent Lancet series on diarrhea suggests that amplification of the current interventions can eliminate virtually all preventable diarrhea deaths. A refocused attention and strategy and collective effort from the multilateral entities to promote water sanitation and hygiene, rotavirus vaccination, nutrition, and improved case management can bridge gaps and tackle the existing undue burden of deaths because of diarrhea. SUMMARY: Investment toward preventing and controlling childhood diarrhea should be a priority, especially when the existing solution is plausible for implementation at scale and in underprivileged settings.

Global burden of childhood diarrhea and interventions.

PURPOSE OF REVIEW: Diarrhea is a leading cause of morbidity and mortality among children under 5 years in low-income and middle-income countries. Over the past 2 decades under-five mortality has decreased substantially, but reductions have been uneven and unsatisfactory in resource-poor regions. RECENT FINDINGS: There are known interventions which can prevent diarrhea or manage children who suffer from it. Interventions with proven effectiveness at the prevention level include water, sanitation, and hygiene interventions, breastfeeding, complementary feeding, vitamin A and zinc supplementation, and vaccines for diarrhea (rotavirus and cholera). Oral rehydration solution, zinc treatment, continued feeding, and antibiotic treatment for certain strains of diarrhea (cholera, Shigella, and cryptosporidiosis) are effective strategies for treatment of diarrhea. The recent Lancet series using the 'Lives Saved' tool suggested that if these identified interventions were scaled up to a global coverage to at least 80%, and immunizations to at least 90%; almost all deaths due to diarrhea could be averted. SUMMARY: The current childhood mortality burden highlights the need of a focused global diarrhea action plan. The findings suggest that with proper packaging of interventions and delivery platforms, the burden of childhood diarrhea can be reduced to a greater extent. All that is required is greater attention and steps toward right direction.

The Immunomodulating Effect of a Diet Consisting of Green Vegetables, Beef, Whole Milk and Full-Fat Butter for Children with Non-Specific Elevated IgE.

BACKGROUND: Non-specific elevated IgE and allergies are common in children, and their prevalence is increasing. Dietary changes could be an explanation for this increase. Zinc, iron, vitamins A, C and E, and polyunsaturated fatty acids all play possible roles in the etiology and possible treatment of allergies due to their numerous immunomodulating properties. OBJECTIVES: To investigate the immunomodulating effect of recommending a nutrient-rich diet consisting of green vegetables, beef, whole milk and full-fat butter. METHODS: We conducted a case-controlled, non-randomized, retrospective study. Children between the ages of 1 and 18 years with non-specific elevated IgE were included. Baseline and follow-up measurements of serum total IgE and clinical outcomes were retrospectively collected and compared for 49 children who received the dietary advice (to eat green vegetables, beef, whole milk and full-fat butter) and 56 children who did not. RESULTS: The initial analysis showed a significantly greater decrease in IgE in the intervention group compared to the control group; a 9.2 kU/l versus a 0.1 kU/l decrease, respectively (P = 0.02). When supplement (vitamin D) use was taken into account, however, no significant difference was produced by the dietary effect alone (unstandardized coefficient = 71.3 kU/l, P = 0.16). 53.2 % of participants in the intervention group reported considerable improvement in symptoms versus 28.6 % in the control group (P < 0.001). CONCLUSION: Overall, the effects of nutrients and vitamins on the decrease in IgE are promising. The separate contributions of dietary advice and/or supplements need to be investigated in the future.

Prenatal and childhood Mediterranean diet and the development of asthma and allergies in children.

OBJECTIVE: To discuss current evidence about the relation between prenatal and childhood Mediterranean diet, and the development of asthma and allergies in children. DESIGN: Review of the literature. SETTING AND RESULTS: Four recent studies conducted in Mediterranean countries (Spain, Greece) and one conducted in Mexico evaluated the association between childhood Mediterranean diet and asthma outcomes in children. All of the studies reported beneficial associations between a high level of adherence to the Mediterranean diet during childhood and symptoms of asthma or allergic rhinitis. Individual foods or food groups contributing to the protective effect of Mediterranean diet included fish, fruits, vegetables, legumes, nuts and cereals, while detrimental components included red meat, margarine and junk food intake. Two studies focused on prenatal Mediterranean diet: the first is a birth cohort in Spain that showed a protective effect of a high adherence to the Mediterranean diet during pregnancy on persistent wheeze, atopic wheeze and atopy at the age of 6.5 years; while the second is a cross-sectional study in Mexico, collecting information more than 6 years after pregnancy, that showed no associations between maternal Mediterranean diet during pregnancy and allergic symptoms in childhood except for current sneezing. CONCLUSIONS: Findings from recent studies suggest that a high level of adherence to the Mediterranean diet early in life protects against the development of asthma and atopy in children. Further studies are needed to better understand the mechanisms of this protective effect, to evaluate the most relevant window of exposure, and to address specific components of diet in relation to disease.

Nutritional intake of children and adolescents with insulin-dependent diabetes mellitus in crete, Greece. A case-control study.

BACKGROUND/AIMS: The incidence of childhood insulin-dependent diabetes mellitus (IDDM) is rapidly increasing in Greece. The aim of this study was to examine nutrient patterns of children and adolescents with IDDM in Crete. METHODS: A case-control survey of eating habits was conducted among 41 children and adolescents, aged 6-17 years, with IDDM (cases) and healthy sex- and age-matched controls, recruited from Heraklion University Hospital and the village of Rouvas, Crete, respectively. Dietary data was based on 24-hour recall records. RESULTS: Dietary intake was similar between the groups. Both groups exceeded the recommendations for total and saturated fat and consumed lower than recommended amounts of dietary fibre and total carbohydrates. Children with IDDM consumed more dairy products and vegetables and less meats and cereals. Vegetables were consumed by a relatively high proportion of children and adolescents in both groups, but there was a higher proportion of fruit consumers amongst the IDDM group. For those who ate fruit and vegetables, intake approximated current recommendations of 400 g/day. CONCLUSIONS: The need to increase complex carbohydrates and reduce the consumption of total and saturated fat, in order to approach the traditional dietary pattern of Crete for this population, should be addressed via appropriate nutrition education programmes.

Growth and host-pathogen interactions.

Differing trajectories of infant and child growth are associated with different patterns of disease and mortality in adulthood. Since postnatal growth patterns are partially modifiable by diet, these associations raise fresh questions about what constitutes an optimal growth rate. We use data from contemporary societies that still suffer poor nutrition and high burdens of infectious disease to illustrate early growth patterns that have likely been typical of our evolutionary past. Pathogenic assault is a major suppressor of growth; populations frequently average -1.0 to -1.5 z scores (standard deviations relative to standard growth curves) for height, and -2.0 to -2.5 z scores for weight, body mass index and head circumference. Many infections are symptomatic (e.g. diarrhea, malaria, pneumonia, HIV), but others are subclinical (e.g. hepatitis B, cytomegalovirus, Epstein-Barr virus, herpes, Helicobacter pylori). The great majority of young children become infected by multiple pathogens which initiate a downward cycle of infection --> suppressed appetite and malabsorption --> reduced growth --> lowered immunity --> repeated infection. Examination of the evolutionary 'norm' for early growth, and the external environmental factors that influenced it, may provide clues towards identifying the current day optimum for growth.

Food allergy: a practical update from the gastroenterological viewpoint.

OBJECTIVE: To present an up-to-date and critical review regarding food allergies, focusing mainly on treatment and prevention. SOURCES: Review of published literature searched on MEDLINE database; those data which were the most up-to-date and representative were selected (2000-2006). The search included the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the American Academy of Pediatrics (AAP). SUMMARY OF THE FINDINGS: The prevalence of allergic diseases has increased over the last decades, and food allergy seems to be part of this increase. Food allergy is much more common in pediatrics and has a significant medical, financial and social impact on young children and their families. Treatment and prevention of food allergy is a major challenge for public health, scientific and medical communities. There is a lot of misinformation and the medical management of this condition is still discussable. We present and discuss the guidelines regarding criteria for the prevention of food allergy and atopic diseases published by the Nutrition Committees of ESPGHAN jointly with the European Society for Pediatric Allergy and Clinical Immunology (ESPACI) and AAP. CONCLUSION: The overdiagnosis of food allergy is quite prevalent. There is a need for standardization of definitions and diagnostic procedures. The primary goal of therapy should be to first establish effective means of preventing food allergies. There is a need for accurate diagnostic methods to confirm or rule out the diagnosis. Patients need appropriate treatment by eliminating foods that cause symptoms, while avoiding the nutritional side effects and the cost of inappropriate diets.

Food allergy: a practical update from the gastroenterological viewpoint / Food allergy: a practical update from the gastroenterological viewpoint

OBJETIVOS: Apresentar uma revisão atualizada e crítica sobre alergias alimentares, focando principalmente em tratamento e prevenção. FONTES DOS DADOS: Revisão da literatura publicada obtida através do banco de dados MEDLINE, sendo selecionados os mais atuais e representativos do tema (2000-2006). A pesquisa incluiu os sites da European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) e American Academy of Pediatrics (AAP). SíNTESE DOS DADOS: A prevalência de doenças alérgicas tem aumentado nas últimas décadas e alergia alimentar parece fazer parte desse aumento. Alergia alimentar é muito mais comum em pediatria e apresenta impacto médico, financeiro e social significativos em crianças menores e suas famílias. Tratamento e prevenção da alergia alimentar são desafios maiores do ponto de vista da saúde pública e para as comunidades médica e científica. Há muita informação incorreta e condutas médicas discutíveis nessa área. Apresentamos e discutimos as recomendações publicadas pelos Comitês de Nutrição da ESPGHAN juntamente com a Sociedade Européia Pediátrica de Alergologia e Imunologia Clínica (ESPACI) e AAP. CONCLUSÃO: Excesso de diagnósticos de alergia alimentar é bastante prevalente. Há necessidade de uniformização de definições e procedimentos diagnósticos. O objetivo primário do manejo deve ser o de instituir medidas efetivas de prevenção das alergias alimentares. Há necessidade de métodos precisos para confirmar ou excluir o diagnóstico. Os pacientes necessitam tratamento apropriado através da eliminação de alimentos que causam sintomas, ao mesmo tempo evitando os efeitos adversos nutricionais e o custo de dietas inadequadas.

OBJECTIVE: To present an up-to-date and critical review regarding food allergies, focusing mainly on treatment and prevention. SOURCES: Review of published literature searched on MEDLINE database; those data which were the most up-to-date and representative were selected (2000-2006). The search included the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the American Academy of Pediatrics (AAP). SUMMARY OF THE FINDINGS: The prevalence of allergic diseases has increased over the last decades, and food allergy seems to be part of this increase. Food allergy is much more common in pediatrics and has a significant medical, financial and social impact on young children and their families. Treatment and prevention of food allergy is a major challenge for public health, scientific and medical communities. There is a lot of misinformation and the medical management of this condition is still discussable. We present and discuss the guidelines regarding criteria for the prevention of food allergy and atopic diseases published by the Nutrition Committees of ESPGHAN jointly with the European Society for Pediatric Allergy and Clinical Immunology (ESPACI) and AAP. CONCLUSION: The overdiagnosis of food allergy is quite prevalent. There is a need for standardization of definitions and diagnostic procedures. The primary goal of therapy should be to first establish effective means of preventing food allergies. There is a need for accurate diagnostic methods to confirm or rule out the diagnosis. Patients need appropriate treatment by eliminating foods that cause symptoms, while avoiding the nutritional side effects and the cost of inappropriate diets.

Oral pathogens and allergic disease: results from the Third National Health and Nutrition Examination Survey.

BACKGROUND: The hygiene hypothesis contends that fewer opportunities for infection have led to increases in the prevalences of asthma and other allergic diseases. OBJECTIVE: This study evaluated the association between asthma, wheeze, and hay fever and antibodies to 2 oral bacteria associated with periodontal disease. METHODS: Data were obtained from the Third National Health and Nutrition Examination Survey. Serum levels of IgG antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were quantified by enzyme-linked immunoassays in 9385 subjects age 12 years and older. The outcomes were current asthma, wheeze, and hay fever. Odds ratios (ORs) representing a 1-log-unit increase in IgG concentrations were estimated with logistic regression. ORs were adjusted for 8 confounders and weighted to represent the US population. RESULTS: For each disease outcome, geometric mean antibody concentrations were higher in persons without the disease outcome than with the disease outcome. For a 1-log-unit increase in P gingivalis antibody concentration, adjusted ORs were 0.41 (95% CI, 0.20-0.87) for asthma, 0.43 (0.23-0.78) for wheeze, and 0.45 (0.23-0.93) for hay fever. For A actinomycetemcomitans, those ORs were 0.56 (0.19-1.72), 0.39 (0.17-0.86), and 0.48 (0.23-1.03), respectively. CONCLUSION: Consistent with the hygiene hypothesis, higher concentrations of IgG antibodies to P gingivalis were significantly associated with lower prevalences of asthma, wheeze, and hay fever, and higher concentrations of IgG antibodies to A actinomycetemcomitans were significantly associated with a lower prevalence of wheeze. CLINICAL IMPLICATIONS: Colonization of the oral cavity by bacteria and other microbes might play a protective role in the etiology of allergic disease.