A Peer-reviewed,
open access bimonthly journal
pISSN 2092-7355   eISSN 2092-7363
    Allergy Asthma Immunol Res. 2023 Sep;15(5):545-561. English.
    Published online Sep 05, 2023.
    https://doi.org/10.4168/aair.2023.15.5.545
    Copyright © 2023 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease
    Review

    Immunonutrition: Diet Diversity, Gut Microbiome and Prevention of Allergic Diseases

    Carina Venter
      • Section of Allergy & Immunology, Department of Pediatrics, Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USA.
    • Correspondence to Carina Venter, PhD, RD. Section of Allergy & Immunology, Department of Pediatrics, Children’s Hospital Colorado, University of Colorado Denver School of Medicine, Anschutz Medical Campus, 13123 East 16th Avenue, Box B518, Aurora, CO 80045, USA. Tel: +1-720-777-6844; Fax: +1-720-777-7247; Email: Carina.Venter@childrenscolorado.org
    Received August 01, 2023; Revised August 22, 2023; Accepted August 23, 2023.

    This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Abstract

    Allergic diseases are increasing both in morbidity and mortality. Genetic, environmental, and dietary factors may all be involved in this increase. Nutrition during pregnancy, breastfeeding, and early life may play a particularly important role in preventing allergic diseases. Based on current systematic reviews, the intake of specific nutrients has failed to prevent allergic disease. Prevention strategies have shifted their focus to the overall diet which can be described using diet diversity. Infant and maternal diet diversity in pregnancy has been associated with reduced allergy outcomes in childhood. Overall, diet also seems to have a marked effect on the microbiome compared to single foods. Factors that may negate the allergy-preventative effect of overall diet diversity include the addition of emulsifiers, advanced glycation end-product content, and overuse of commercial baby foods. There is a need to perform randomized controlled trials using overall dietary intake to support international food allergy guidelines. These studies should ideally be conducted by multi-professional teams.

    Keywords
    Diet diversity; dietary diversity; food diversity; nutrients; microbiome; food allergy; asthma; dermatitis, atopic; eczema; allergic rhinitis

    INTRODUCTION

    Allergic diseases are considered to be an increasing public health concern. The 4 major presentations of allergic diseases include asthma, eczema, allergic rhinitis, and food allergies. Allergies negatively impact the quality of life, school performance, and income,1 and may be fatal.2, 3 Different allergies often co-exist as they share a common immunoglobulin E (IgE)-mediated pathogenesis.4, 5, 6 Asthma is estimated to affect 300 million people worldwide7 and 10.4% of children in the US.8 Allergic rhinitis is estimated to affect up to 40% of children worldwide9 and around 13% of US children.9 Eczema/atopic dermatitis affects 15%-30% of children worldwide, with a lifetime prevalence of 10%–20% in US children.10 Food allergy prevalence across the globe ranges between 1.1% and 10.4%.1 The latest data from the US indicate that 7.6% of children develop a food allergy.11

    Interventions aiming to reduce allergy outcomes have included interventions during pregnancy, lactation, and early life. Dietary interventions included food allergen introduction or avoidance, prebiotic intake, probiotic intake, nutrient supplementation, or intake of specific foods.12 The developmental origins of health and disease hypothesis suggest that maternal nutritional intake during pregnancy and breastfeeding as well as infant nutrition may have a significant impact on the risk of developing non-communicable diseases throughout life. A recent European Academy of Allergy and Clinical Immunology (EAACI) systematic review15 with meta-analysis summarized studies investigating the association between food patterns and intake of single foods and nutrients during pregnancy on the development of offspring allergic rhinitis, atopic dermatitis, asthma, wheezing, and food allergy. The review included studies focusing on all aspects of dietary intake. Overall, the review showed only one significant association: a reduction in offspring asthma following maternal vitamin D supplementation in pregnancy.14, 15, 16 A thorough systematic review conducted on behalf of the Food Standards Agency, UK, focusing on nutritional factors during pregnancy, lactation, and early life concluded that maternal probiotic and fish oil supplementation may reduce the risk of eczema and allergic sensitization to food, respectively. No recommendations were made regarding the overall diet during breastfeeding and the infant diet. Neither of these reviews included diet patterns or overall diet in their searches.

    These systematic reviews highlighted that single nutrients or foods during pregnancy may show some association with offspring allergy and respiratory outcomes. However, the problems with the research and conclusions may be that nutrients and foods are not eaten in isolation. In support of this, the 2020–2025 Dietary Guidelines for Americans state that dietary patterns may better predict overall health status and disease risk than individual foods or nutrients.17 To increase our understanding of the complex relationship between nutrients and other essential components of food, there has been a growing interest in a whole diet approach when studying disease outcomes. To summarize a whole diet, either diet indices as a proxy for diet patterns or diet diversity as a proxy for diet variety may be used.18 Diet indices or diet patterns such as the Mediterranean diet, healthy diet17 or prudent diet (characterized by a high intake of vegetables, fruit, legumes, whole grains, and fish and other seafood), plant-based diet (includes fruits and vegetables, nuts, seeds, oils, whole grains, legumes, and beans) or flexitarian diet (a semi-vegetarian style of eating that supports eating less meat and more plant-based food may also be used. This paper focuses on diet diversity. It is also important that the mechanisms through which the overall diet may affect allergy outcomes should be considered. These factors are the microbiome, epithelial barrier, immune system, and epigenetics.

    Allergies are epithelial diseases affecting the epithelia of the gut, skin, lungs, nose, and ear. The gut barrier plays an important role in early life to prevent allergic diseases. The gut barrier is composed of the gut microbiome, the mucus and epithelial layers, and the immune system. There is a complex interplay between all these factors to prevent allergic outcomes. A range of nutritional elements can affect different aspects of the epithelial barrier of the gut, and these should be considered in studies focusing on diet diversity. Nutrition can affect the intestinal barrier via changes in gut microbiota composition (species and diversity) and function (formation of components and metabolites), direct effects on the intestinal epithelium, and impacts on the intestinal immune system.

    Immunonutrition has its roots in treating the critically ill and can generally be defined as the study of the direct and indirect effects of nutrients, including macronutrients, vitamins, minerals, and trace elements on immune system development, functionality, and responsiveness.19 The recent developments in “omics” technologies have made it possible to study nutrient interactions within the overall diet by examining the host microbiome, immune system, epigenetics, and disease outcomes. This increased knowledge enables us to study these interactions. This “complicated tango” between nutrients, microbiome, epithelial barriers, metabolism, and the immune system is crucial for disease prevention.20 With our increased understanding, an updated definition may be required to include the broader role of nutrition, e.g., immunonutrition can generally be defined as the study of the direct and indirect effects of food patterns/quality, food diversity, foods, nutrients, microbiome, epigenetics, epithelial barriers, metabolism, and the immune system development, functionality, and responsiveness. There is an urgent need to increase our knowledge on the effects of nutrients on the immune system, especially the basic mechanisms and processes underpinning immunonutrition.

    Long-chain fatty acids,21 vitamins, and fiber22 are particularly known for their important role in immune outcomes.23 Yet, none of these nutrients used as an individual diet strategy reduced allergy outcomes, highlighting the importance of focusing on overall diet strategies. Diet diversity seems to be a promising measure of overall dietary intake leading to increased microbial diversity and subsequent reduced allergy outcomes.24 Data regarding overall dietary intake focusing on food patterns or diet quality has also shown the potential to positively affect the microbiome, immune system, and disease outcomes.25 This paper will focus on the role of diet diversity during pregnancy, lactation, and infancy and allergic diseases in childhood.

    DIET DIVERSITY

    Diet diversity is defined as the number of foods or food groups consumed over a given reference period.26 Diet variety is considered synonymous with diet diversity.26 Diet diversity can be measured by summing the number of foods,27, 28, 29, 30, 31, 32, 33 food groups,27, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 or foods within a food group,49, 50, 51, 52 e.g., number/range of vegetables eaten.53 Diet diversity can be measured over any period of time ranging from, e.g., one meal, one day or one year.20 The EAACI suggests that diet diversity can be defined as the intake of food groups (e.g., food allergens) or nutrients (e.g., fiber).18 The report also suggests the time period, frequency, and portion sizes/amount consumed should be stated. Diet diversity has been associated with 1) nutrient intake or 2) nutritional status, and gradients of socioeconomic status.18, 31, 48, 54

    DIET DIVERSITY AND THE MICROBIOME

    In an animal model, Sullivan et al. 55 demonstrated that the small intestine adjusts to diets with different macronutrient (protein, carbohydrate, fat) compositions through cellular adaptation of the intestinal epithelium and changes in lymphocyte-epithelial regulation. In addition, diet is estimated to account for 20% of the variations seen in the human gut microbiome.56 Therefore, diet, especially diet diversity encompassing macronutrient intake, can change the microbiome and gut epithelial immune indices. Despite the potential of diet diversity to greatly affect the gut microbiome structure and function and subsequent immune outcomes, there is surprisingly little evidence about the role of diet diversity on the microbiome. Most information available comes from adult or elderly studies.

    Adults

    Xiao et al. 57 analyzed data from 1,916 participants (average age, 59.2 years) in the Guangzhou Nutrition and Health Study (GNHS) from South China, replicated their data using data from the China Health and Nutrition Survey (CHNS) (n = 1,320; average age, 48.2 years), across China. Participants in both cohorts completed food frequency questionnaires covering over 70 foods in the previous year, assigning each food to 6 food groups: grains, vegetables, fruits, dairy and dairy products, legumes and legume products, and meat and meat alternatives (including fish, eggs, and nuts). If participants reported eating ≥2 servings per week, 1 point was assigned and then summed to provide a dietary diversity from 0 to 6. In the GNHS cohort, 53% of participants received a score of ≥6, and 34% in the CHNS cohort. Comparing this group to those obtaining a score of <6, the authors found positive associations between dietary diversity and multiple gut microbial diversity metrics as well as microbiome composition. Anaerotruncus and Veillonella were enriched in those with high dietary diversity scores. Metabolomic profiling of stool and serum samples in the GNHS cohort revealed associations of dietary diversity with fecal metabolites, glycodeoxycholic acid, taurodeoxycholic acid, glycolithocholic acid 3-sulfate, and nordeoxycholic acid.

    Data from 1,800 adults from the American Gut study indicated that diet patterns such as the Prudent-like diets (Plant-Based and Flexitarian) were associated with increased beta-diversity compared to individual macronutrients (e.g., fiber and protein).58 Alpha diversity was also increased in the Flexitarian pattern compared to the Western diet pattern. The exclusion of single macronutrients, e.g., a low carbohydrate diet, was associated with low relative abundance of Bifidobacterium.

    Elderly

    Amamoto et al. 59 analyzed the relationships between dietary diversity and gut microbiota diversity in 445 Japanese subjects (65–90 years). Diet diversity showed significant positive relationships with 2 α-diversity indices, Pielou’s evenness and Shannon indices, indicating uniformity of species distribution. The data, therefore, suggests that a more diverse diet is associated with a more uniform abundance of a range of bacterial groups rather than a greater variety of gut bacteria. Diet diversity also showed significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) such as butyrate, shown to have an allergy-preventative effect. A negative association was found with the abundance of Ruminococcus gnavus group, which produces inflammatory polysaccharides. Comparing the age groups < 75 years vs. ≥ 75 years suggested that the effect on the SCFA bacteria was only seen up to 75 years. This was supported by a study from Ireland, indicating that increased diet diversity in the elderly was associated with increased gut microbial diversity and reduced frailty.60

    Infants

    The act of food introduction changes the gut microbiome composition and function, making it difficult to study the true effect of diet diversity on the infant gut microbiome. One study reported that the gut microbiome of the growing infant shows increased alpha-diversity and reduced beta-diversity in the gut microbiota of the growing infant, pointing to the development of a more complex and less dissimilar. Cessation of breastfeeding, rather than solid food introduction, drives the maturation of the infant gut microbiome.61 However, using the process of solid food introduction as a proxy for diet diversity, Homann et al. 62 studied gut microbiome diversity over 2 weeks around the time of solid food introduction. Daily diet diversity was defined as the consumption of foods from the following groups: the food groups specified in this study were fruit, vegetables, grains (including beans and legumes), meat, dairy, confections/desserts, and oils. Beans and legumes were included in the grain category to differentiate between meat and vegetarian protein. Day-to-day changes in the gut microbiome of 24 healthy, full-term infants from the Baby, Food & Mi, and LucKi-Gut cohort studies64 were described. Microbial richness (species) and Shannon diversity (alpha diversity) increased over time as dietary diversity increased. Beta-diversity was negatively associated with increased dietary diversity, indicating that high daily dietary diversity stabilized the gut microbiome. Bifidobacterial taxa were positively associated with dietary diversity in both cohorts. In this study, dietary diversity seems to have the greatest impact on the gut microbiome as solids are introduced. In support of this study, increased intake of family foods as a measure of diet diversity during the first year of life has also been associated with increased gut microbiome diversity using the Shannon alpha diversity index.63

    Data from the PASTEUR study indicated that a diet rich in fruit, vegetables, fish, and yogurt led to increased production of butyrate in infancy and was associated with reduced allergy outcomes at 6 years.64 Butyrate production plays a role in oral tolerance development through its effect on T regulatory cells, which downregulates Th2 cytokine production65 and modulates immune-regulating components in the gut and tissues.66, 67, 68, 69, 70

    A Korean study reporting on egg allergy at 2 years of age in high-risk infants (defined as having a family history of allergy) showed that higher diet diversity scores in very early infancy (3–5 months) were associated with an increase in microbial diversity at 6 months using the Chao1 index.71 Also, gene expressions of pro-inflammatory and Th2-cytokines and chemokines were higher in infants with low diversity than high diversity scores, but only in the high-risk group. The Enquire About Tolerance (EAT) study indicates that increased food allergen diversity in the first year of life was associated with a significant increase in alpha diversity and increased levels of Proteaceae and proteobacteria.72

    FACTORS TO CONSIDER WHEN MEASURING DIET DIVERSITY

    The unequivocal association between dietary intake and disease outcomes is hindered for several reasons. It is difficult to accurately study nutritional intake in real-world settings over extended periods due to a limited range of validated tools, particularly those focusing on food allergen intake. It is unclear to what extent an individual’s nutritional status prior to a dietary intervention may affect associations or lack of associations. There is a lack of studies focusing on all aspects of the immunomodulation pathway, including the microbiome, epithelial barriers, immune indices, and disease outcomes, and how this may be affected by diet diversity. Moreover, future studies need to reach a consensus on how to define dietary diversity, and supportive functional and experimental studies are required to determine whether and how dietary diversity could be modified to optimize the human microbiome.

    DIETARY FACTORS THAT MAY AFFECT ALLERGY PREVENTION

    Foods containing emulsifiers

    The increase in the prevalence and severity of many allergic diseases has been associated with damage to the epithelial layer, likely induced through exposures to a range of environmental factors and diet. Studies have shown that emulsifiers present in processed food increase intestinal permeability, leading to mucosal damage.73 Emulsifiers such as carboxymethylcellulose (CMC) and polysorbate-80 have been shown to impair gut barrier function, leading to metabolic abnormalities and low-grade inflammation or colitis in wild-type mice or genetically susceptible mice, respectively, which was linked to the gut microbiome.74 Additional murine studies showed similar findings for another emulsifier, glycerol monolaurate.75

    Ultra-processed foods (UPFs)

    A number of human observational studies indicated changes in gut microbiome composition and function in those consuming UPFs. Particularly, high levels of UPF consumption in the highest tertile were associated with changes in microbial taxa.76 In addition, CMC consumption in humans has been shown to significantly alter gut microbiota composition, reduce fecal SCFA levels, and support bacterial encroachment into the mucus layer.74 A small pilot study, including 4 couples, showed that limiting intake of UPFs, such as processed meats, carbonated beverages, and snacks, can change the composition of the microbiota. Still, larger, more robust studies are required.77

    Use of infant foods

    Knight et al. 78 questioned if the low pH found in commercial baby foods, particularly those with fruit or citric acid added, may be driving the increase in diseases related to epithelial injury. The majority of infant/toddler foods containing fruit and vegetables in their study had a low pH, including some of the infant/toddler meals, particularly those with fruit, vitamin, and/or citric acid. The authors hypothesized that frequent consumption of commercial infant and toddler foods, with added acidic fruit and/or citric acid, negatively affects esophageal epithelium integrity and that their widespread availability in a form requiring no or limited chewing may be a further contributing factor.

    Another concern of infant food is the possible lack of diversity. From the existing data, it is currently unclear if using a predominant commercial infant food is likely to be less diverse than a home-made diet. However, frequent consumption of fruit purees and juices in commercial infant foods may lead to reduced diet diversity in later childhood. There may also be reduced intake of immunomodulatory nutrients in infants fed a predominant commercial infant food.79 In fact, an Australian study indicated that commercial infant products were poor sources of iron, and 80% of first foods were fruit-based.80 In addition, from 251 Australian commercial baby foods surveyed, only 1% contained eggs, and none had peanuts. This low food allergen content may be problematic for infants fed primarily commercial infant foods as they are unlikely to be exposed to sufficient amounts of the major food allergens frequently.81

    DIET DIVERSITY AND ALLERGY OUTCOMES

    Diet diversity in pregnancy

    Only one study has explored an association between diet diversity in pregnancy and childhood allergy outcomes.82 In this study looking at maternal diet diversity in pregnancy and childhood allergies at 4 years, the adjusted models showed that increases in maternal healthy diet diversity were significantly associated with reduced odds of overall allergy, atopic dermatitis, asthma, and wheeze in their children. Increases in maternal unhealthy diet diversity scores were significantly associated with higher odds of atopic dermatitis in their children. Total diet diversity, including healthy and unhealthy diversity, during pregnancy, did not show an association with any child allergic outcomes. Healthy diet diversity showed a similar area under the curve for most allergies (Figure).

    Figure
    The Association between different measures of diet diversity and diet indices in pregnancy and offspring allergy outcomes. Diet diversity and indices in pregnancy. Reprinted with permission from Venter et al.82 OR, odds ratio; CI, confidence interval; ROC, receiver operating characteristic.

    Diet diversity during infancy

    Food allergen sensitization

    Roduit et al. 83 (Table) reported the association between diet diversity and food allergen sensitization in the Protection Against Allergy Study in Rural Environments (PASTURE) prospective cohort.

    Table
    Diet diversity in infancy and allergy outcomes

    Children aged 4.5 or 6 years, with lower diet diversity, had an increased risk of sensitization to food allergens. Nwaru and colleagues84 reported that reduced diet diversity in a Finnish birth cohort was associated with an increased risk of sensitization to specific food allergens at 2 years.

    In a study from the UK, Venter et al. 53 reported that higher diet diversity at month 6 decreased the odds of being sensitized to a predefined panel of food allergens at one year and over the first 10 years of life. Higher diet diversity at month 9 decreased the odds of food sensitization at 2 and 3 years. In addition, higher cumulative DD (6 + 9 months) decreased the odds of food sensitization at year 1, year 2, and year 3.

    Aeroallergen sensitization

    Two studies investigated the association between diet diversity and aeroallergen sensitization. In the PASTEUR study, Roduit et al. 83 found no association between diet diversity in the first year of life and aeroallergen sensitization at 4.5 and 6 years. Markevych et al. 88 reported that a reduced prevalence of aeroallergen sensitization in a German birth cohort was seen for up to 15 years with increased diet diversity in the first year of life.

    Food allergy

    1. Diet diversity in observational studies

    Four observational studies in infancy reported the association between diet diversity in infancy and the development of food allergy during childhood. Roduit et al. 83 reported a significant association between higher diet diversity and a lower prevalence of parent-reported, doctor-diagnosed food allergy. In this cohort, diet diversity in the second year of life was not associated with food allergy at 6 years,97 indicating that diet diversity in early life may be more important than in later childhood. However, at 2 years, increased intake of yogurt and cow’s milk was associated with reduced food allergy at 6 years. Data from the Isle of Wight indicated that increased diet diversity at 6 and 9 months was significantly associated with reduced odds of food allergy by 10 years of age.53 Food allergy diagnosis was based on an oral food challenge and/or a good clinical history with IgE sensitization to the food. For every additional food introduced by 6 months, the odds were reduced by 10%. Using the World Health Organization (WHO) definition of diet diversity and diversity of fruit and vegetables consumed by 6 months, a significant reduction in the odds of developing food allergy by 10 years was seen. By 10 years of age, there was also a significant association between food allergen diversity by 12 months and food allergy. For each additional food allergen introduced by 12 months, the odds of food allergy were reduced by 33%. A median number of 11 foods (range 0–21), 2 food allergens (range 0–8), and 3 fruit and vegetables (range 0–5) were consumed by 6 months. Children consumed a median of 5 allergens (range 0–8) by 12 months.

    A study from China compared consumption of 1–5 food groups vs. 8–11 food groups.87 In this study, lower food diversity at 12 months was significantly associated with an increased risk of parent-reported doctor’s diagnosis of food allergy by 2 years. Lee et al. (Korea)71 showed that higher diet diversity based on food group consumption, food allergen consumption, and the WHO diversity scores at 3 and 4 months lead to a significant reduction in the risk of developing hen’s egg allergy in the high-risk group (defined as a family history of food allergy), but not in the control group. No further associations were found between diet diversity at 6 months and food allergy outcomes at 2 years.

    2. Fruit and vegetable diversity

    Venter et al. 53 reported (UK) that fruit and vegetable diversity at 6 and 9 months significantly reduced the odds of food allergy by 10 years of age.

    3. Food allergen diversity in randomized controlled trials (RCTs)

    The EAT study reported that introducing food allergens from as early as 3 months in a general breastfed population cohort led to significant risk reductions in food allergy to eggs and peanuts in the per-protocol analysis.98 The EAT study could be considered a study on food allergen diversity, as 6 common food allergens were introduced during infancy. Still, data on allergen diversity in the control vs. active group have not been reported.98

    In a RCT, Quake et al. 99 fed infants single food allergens (milk, egg, or peanut as 300 mg protein per day: 2,100 mg protein/food allergen/week) or 2 food allergens (milk/egg, egg/peanut, milk/peanut as 300 mg per mix per day: 1,050 mg protein/food allergen/week) or a multiple food allergen mix of 10 food allergens (milk/egg/peanut/cashew/almond/shrimp/walnut/wheat/salmon/hazelnut at low [300 mg per day: 21 (3 mg × 7) mg/food allergen/week], medium [63 (9 mg × 7) mg/food allergen/week], or high doses [210 (30 mg × 7) mg/food allergen/week]) vs. no allergen introduction in infants between 4–6 months of age. All infants were breastfed upon study entry. Significantly more children in the allergen mixture arms were able to consume 8 g of total allergen intake than the control group (P < 0.01).

    Atopic dermatitis

    Nine studies from Asia, Europe, and Oceania (Korea, Germany, Italy, New Zealand, Finland, Austria, France, and Switzerland) investigated the association between diet diversity in infancy and childhood eczema/atopic dermatitis. The GINIPlus and LISA studies showed that very early higher diet diversity before 4 months was associated with an increased risk of atopic dermatitis at 2 and 6 years, but no association was found at 4 years.89 The LISAplus study indicated an increased risk of atopic dermatitis at 2 years with less diet diversity at 4 months.90, 91 No association was found between diet diversity at 4 months and atopic dermatitis at 6 years.90, 91 LISAplus birth cohort showed that children in the highest quartile (all 8 foods) of diet diversity vs. the lowest quartile (maximum of 5 foods) during the first year of life had lower odds of developing atopic dermatitis up to age 15 years.88 Lower diet diversity at 6 and 12 months in a Finnish cohort was associated with an increased risk of atopic dermatitis at 5 years.85 Increased diet diversity within the 1st year of life was associated with a reduced risk of developing atopic dermatitis up to 4 years in the PASTEUR study.100 A study from China reported reduced skin allergies up to 2 years in children with a higher diet diversity by 6 and 12 months.89 In a case-control study from Italy, the authors reported that increased diet diversity at 4 and 5 months was associated with a reduced risk of atopic dermatitis by 2 years of age.92

    In contrast with the other studies, a New Zealand birth cohort indicated that a more diverse diet during the first 4 months of life was associated with an increased risk of developing atopic dermatitis at 2 and 3 years and an increased risk of recurrent atopic dermatitis at 10 years.93, 94, 95, 96

    Asthma and allergic rhinitis

    Data from 2 European cohorts and one Asian cohort are available; the PASTURE study,83 the Finnish Type I Diabetes Prediction and Prevention Study Prospective Cohort Study,85 and a Chinese cohort.87 Roduit et al. 83 indicated in the PASTEUR study that increased diet diversity in the first year of life was associated with a reduced risk of developing asthma. The odds of developing asthma were reduced by 26% for each additional food introduced. Diet diversity did not seem to protect against allergic rhinitis. Nwaru et al. 85 reported in the Finnish Type I Diabetes Prediction and Prevention Study that lower diversity at 12 months of life was associated with an increased risk for asthma and wheezing at 5 years. However, reduced diet diversity at 6 and 12 months was significantly associated with the risk of developing allergic rhinitis at 4 years. A Chinese study reported that higher diet diversity by 6 and 12 months was associated with reduced prevalence of respiratory allergies up to 2 years.87

    In summary, most studies indicate that the higher diet diversity was associated with reduced allergy outcomes. It is important to note the association between higher diet diversity before 4 months and increased allergy outcomes when solid food intake is not recommended yet.

    UNMET NEEDS

    Clearly, the tsunami of allergic diseases requires detailed studies investigating the role of nutritional, environmental, and lifestyle factors that may underpin the immune dysfunction seen. We are in need of well-conducted RCTs with clear methodologies, bringing together expertise from dietitians, nutritionists, immunologists, microbiologists, allergists, and biotechnicians. Research priorities should include 1) nutrition, focusing on the overall diet and allergic disease prevention, 2) assessment of nutritional status and nutritional intake prior to intervention studies, 3) evaluation of the effects of nutrients, foods, and food patterns on the microbiome, epithelial barrier, epigenetics, and immune status, 4) evaluation of lifestyle factors as possible adjuvant factors to the overall diet, expressed as diet diversity in disease prevention, and 5) a critical understanding of diet diversity and if different definitions should be used for allergic disease prevention vs. management.

    SUMMARY AND THE FUTURE

    While environmental or other lifestyle changes are difficult to change, diet remains a modifiable factor that can be used to prevent or manage allergic disease. Diet diversity is a useful measure to describe overall dietary intake. Diet diversity in pregnancy, focusing on healthy foods, and infancy is reported to reduce offspring allergy outcomes. Allergen diversity and food group diversity such as fruit and vegetables in infancy may also lead to reduced childhood food allergies. There is a need to harmonize study methods and define diet diversity for studying dietary intake, allergy outcomes, and the underlying mechanisms. There is a lack of RCTs in this field. Providing dietary support and information to increase diet diversity during pregnancy and early childhood can play an important role in preventing allergies. To fully address the concept of diet diversity within the field of immunonutrition, we need to 1) identify knowledge gaps about the effects of nutrition on allergic outcomes, 2) study the overall diet with the supporting mechanisms, and 3) support education, training, and research in this fast-developing field.

    Notes

    Disclosure:Dr. Venter reports grants from Reckitt Benckiser, grants from Food Allergy Research and Education, grants from National Peanut Board, during the conduct of the study; personal fees from Bobbi, Reckitt Benckiser, personal fees from Nestle Nutrition Institute, personal fees from Danone, personal fees from Abbott Nutrition, personal fees from Else Nutrition, and personal fees from Before Brands, outside the submitted work.

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    MeSH Terms
    Asthma
    Breast Feeding
    Dermatitis, Atopic
    Diet*
    Eating
    Eczema
    Food Hypersensitivity
    Gastrointestinal Microbiome*
    Humans
    Hypersensitivity
    Infant
    Microbiota
    Mortality
    Pregnancy
    Prenatal Nutritional Physiological Phenomena
    Rhinitis, Allergic
    Systematic Review
    Metrics
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