Download as pdf or txt
Download as pdf or txt
You are on page 1of 17

Allergy Asthma Immunol Res.

2023 Sep;15(5):545-561
https://doi.org/10.4168/aair.2023.15.5.545
pISSN 2092-7355·eISSN 2092-7363

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

Received: Aug 1, 2023


Revised: Aug 22, 2023
ABSTRACT
Accepted: Aug 23, 2023
Published online: Sep 5, 2023 Allergic diseases are increasing both in morbidity and mortality. Genetic, environmental,
and dietary factors may all be involved in this increase. Nutrition during pregnancy,
Correspondence to
breastfeeding, and early life may play a particularly important role in preventing allergic
Carina Venter, PhD, RD
diseases. Based on current systematic reviews, the intake of specific nutrients has failed
Section of Allergy & Immunology, Department
of Pediatrics, Children’s Hospital Colorado, to prevent allergic disease. Prevention strategies have shifted their focus to the overall diet
University of Colorado Denver School of which can be described using diet diversity. Infant and maternal diet diversity in pregnancy
Medicine, Anschutz Medical Campus, 13123 has been associated with reduced allergy outcomes in childhood. Overall, diet also seems to
East 16th Avenue, Box B518, Aurora, CO 80045, have a marked effect on the microbiome compared to single foods. Factors that may negate
USA.
the allergy-preventative effect of overall diet diversity include the addition of emulsifiers,
Tel: +1-720-777-6844
Fax: +1-720-777-7247 advanced glycation end-product content, and overuse of commercial baby foods. There
Email: Carina.Venter@childrenscolorado.org 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-
Copyright © 2023 The Korean Academy of
professional teams.
Asthma, Allergy and Clinical Immunology •
The Korean Academy of Pediatric Allergy and
Keywords: Diet diversity; dietary diversity; food diversity; nutrients; microbiome;
Respiratory Disease
food allergy; asthma; dermatitis, atopic; eczema; allergic rhinitis
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
INTRODUCTION
use, distribution, and reproduction in any
medium, provided the original work is properly Allergic diseases are considered to be an increasing public health concern. The 4
cited. major presentations of allergic diseases include asthma, eczema, allergic rhinitis, and
food allergies. Allergies negatively impact the quality of life, school performance, and
ORCID iDs
Carina Venter income,1 and may be fatal.2,3 Different allergies often co-exist as they share a common
https://orcid.org/0000-0002-7473-5355 immunoglobulin E (IgE)-mediated pathogenesis.4-6 Asthma is estimated to affect 300 million
people worldwide7 and 10.4% of children in the US.8 Allergic rhinitis is estimated to affect
Disclosure
up to 40% of children worldwide9 and around 13% of US children.9 Eczema/atopic dermatitis
Dr. Venter reports grants from Reckitt
Benckiser, grants from Food Allergy Research
affects 15%-30% of children worldwide, with a lifetime prevalence of 10%–20% in US
and Education, grants from National Peanut children.10 Food allergy prevalence across the globe ranges between 1.1% and 10.4%.1 The
Board, during the conduct of the study; latest data from the US indicate that 7.6% of children develop a food allergy.11

https://e-aair.org 545
Diet Diversity and Allergy

personal fees from Bobbi, Reckitt Benckiser, Interventions aiming to reduce allergy outcomes have included interventions during
personal fees from Nestle Nutrition Institute, pregnancy, lactation, and early life. Dietary interventions included food allergen introduction
personal fees from Danone, personal fees
or avoidance, prebiotic intake, probiotic intake, nutrient supplementation, or intake of
from Abbott Nutrition, personal fees from
Else Nutrition, and personal fees from Before
specific foods.12 The developmental origins of health and disease hypothesis suggest that
Brands, outside the submitted work. 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.14-16 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

https://e-aair.org https://doi.org/10.4168/aair.2023.15.5.545 546


Diet Diversity and Allergy

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,27-33 food groups,27,34-48 or foods within a
food group,49-52 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.

https://e-aair.org https://doi.org/10.4168/aair.2023.15.5.545 547


Diet Diversity and Allergy

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

https://e-aair.org https://doi.org/10.4168/aair.2023.15.5.545 548


Diet Diversity and Allergy

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.66-70

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

https://e-aair.org https://doi.org/10.4168/aair.2023.15.5.545 549


Diet Diversity and Allergy

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

https://e-aair.org https://doi.org/10.4168/aair.2023.15.5.545 550


Diet Diversity and Allergy

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).

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.

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.

https://e-aair.org https://doi.org/10.4168/aair.2023.15.5.545 551


Diet Diversity and Allergy

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.

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

https://e-aair.org https://doi.org/10.4168/aair.2023.15.5.545 552


Diet Diversity and Allergy

Table. Diet diversity in infancy and allergy outcomes


Allergy Timing of diet diversity Outcome Diet diversity definition Risk
outcome
Food allergen Increased diet diversity in the first year of life 4.5 and 6 years83 PASTURE: 6 food items (vegetables or fruits, cereals, bread, meat, Decreased
sensitization cake, and yogurt)
Increased diet diversity in the first year of life 5 years84,86 Finland: cow’s milk and infant formula; potatoes; carrots; turnip; Decreased
fruits and berries (as a combined variable); cereals (rye, wheat,
oats, and barley as a combined variable); other cereals (maize,
rice, millet, and buckwheat as a combined variable), meat; fish;
egg; cabbage; spinach; and lettuce
Increased diet diversity in the first year of life up to 10 years86 UK: 21 foods commonly introduced in the first year of life, Decreased
including fruits, vegetables, meat and poultry, grains, egg, and
milk products as well as the major food allergens
Increased diet diversity in the first year of life up to 2 years87 China: 6 food groups (cereals, vegetables, fruits, meats, fish, Decreased
and eggs) at 6-month interview and 11 food groups (cereals,
vegetables, fruits, meats, fish and seafood, eggs, beans, peanut,
other nuts, milk and milk products, and sweets)
Increased diet diversity in the first year of life up to 2 years71 Korea: 10 food groups (grains, vegetables, fruits, meat, fish, eggs, Decreased
dairy, wheat, peanuts, and legumes/nuts) were enquired about at
12 months
Inhalant Increased diet diversity in the first year of life up to 15 years88 Germany: 48 food items were grouped into 8 food groups: Decreased
allergen 1) vegetables (avocado, cauliflower, beans, broccoli, peas,
sensitization cucumbers, carrots, potatoes, white cabbage, turnip, cabbage,
lenses, celery, asparagus, spinach, tomatoes, onion, vegetable
juices); 2) fruits (apples, pineapples, apricots, bananas, pears,
strawberries, peaches, citrus fruit, fruit juices); 3) cereal (bread/
pretzels/rolls, cookies/cakes/rusk, rolled oats, muesli, millet,
cornmeal/corn starch, wheat semolina/starch, noodles, rice/rice
starch, spelt); 4) meat (poultry, lamb, veal/beef, pork, sausages);
5) egg; 6) dairy products (cow milk/cream, yogurt/quark/cheese);
7) fish; and 8) other (nuts, soy products, cocoa/chocolate)
Increased diet diversity in the first year of life 4.5 and 6 years83 No association
Food allergy Increased diet diversity in the first year of life up to 6 years83 Decreased
Increased diet diversity in the first year of life up to 2 years87 Decreased
Increased diet diversity in the first year of life up to 2 years71 Decreased
Increased diet diversity in the first year of like up 10 years53 UK: 21 foods commonly introduced in the first year of life, Decreased
including fruits, vegetables, meat and poultry, grains, egg, and
milk products as well as the major food allergens
Atopic Increased very early diet diversity before 4 4 years89 Germany: Increased
dermatitis months LISA: see above
GINI: dairy products, eggs, cereals, legumes, vegetables, fruits,
nuts, meat products, fish, and other foods
Increased very early diverse diet by 4 months 6 years90,91 Increased
Extreme intakes of diet diversity in the first 15 years88 Decreased
year of life
Overall diet diversity No association
Increased diet diversity at 12 months 1 and 5 years85 No association
Increased diet diversity in the first year of life 4 years83 Decreased
Increased diverse diet by 4 and 5 months 2 years92 9 food groups: vegetables, legumes, or roots (potatoes, carrots, Decreased
tomatoes, and beans), fruits (apples, pears, peaches, apricots,
plums, citrus fruits, red fruits), cereals (maize/tapioca, rice,
pasta, and gluten-free pasta), meat (poultry, pork, and beef),
dairy products (cheese, and other dairies), fish, eggs, and nuts/
cacao/chocolate
Increased diet diversity in the first year 2 years71 Decreased
Increased diet diversity at 4 months 2, 4, 10 years93-96New Zealand: cow’s milk, cereals, vegetables, dairy products, Increased
meat, fruit, egg/related products, other foods
Asthma Increased diet diversity by 3, 4, 6 months 5 years85 Decreased
Increased diet diversity in the first year of life 4 years83 Decreased
Increased diet diversity in the first year of life up to 2 years87 Decreased
Rhinitis Increased diet diversity at 3, 4, 6 months 5 years85 Decreased
Increased diet diversity in the first year of life 4 years83 No association

https://e-aair.org https://doi.org/10.4168/aair.2023.15.5.545 553


Diet Diversity and Allergy

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.93-96

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

https://e-aair.org https://doi.org/10.4168/aair.2023.15.5.545 554


Diet Diversity and Allergy

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.

REFERENCES
1. Muraro A, Dubois AE, DunnGalvin A, Hourihane JO, de Jong NW, Meyer R, et al. EAACI food allergy and
anaphylaxis guidelines. Food allergy health-related quality of life measures. Allergy 2014;69:845-53.
PUBMED | CROSSREF
2. Dwyer-Lindgren L, Bertozzi-Villa A, Stubbs RW, Morozoff C, Shirude S, Naghavi M, et al. Trends and
patterns of differences in chronic respiratory disease mortality among US Counties, 1980-2014. JAMA
2017;318:1136-49.
PUBMED | CROSSREF
3. Turner PJ, Gowland MH, Sharma V, Ierodiakonou D, Harper N, Garcez T, et al. Increase in anaphylaxis-
related hospitalizations but no increase in fatalities: an analysis of United Kingdom national anaphylaxis
data, 1992-2012. J Allergy Clin Immunol 2015;135:956-963.e1.
PUBMED | CROSSREF
4. Akdis M, Aab A, Altunbulakli C, Azkur K, Costa RA, Crameri R, et al. Interleukins (from IL-1 to IL-38),
interferons, transforming growth factor β, and TNF-α: receptors, functions, and roles in diseases. J
Allergy Clin Immunol 2016;138:984-1010.
PUBMED | CROSSREF
5. Ballardini N, Bergström A, Wahlgren CF, van Hage M, Hallner E, Kull I, et al. IgE antibodies in relation
to prevalence and multimorbidity of eczema, asthma, and rhinitis from birth to adolescence. Allergy
2016;71:342-9.
PUBMED | CROSSREF
6. Campbell DE, Boyle RJ, Thornton CA, Prescott SL. Mechanisms of allergic disease - environmental and
genetic determinants for the development of allergy. Clin Exp Allergy 2015;45:844-58.
PUBMED | CROSSREF
7. Pawankar RC, Holgate ST, Canonica GW, Lockey RF, Blaiss M. The WAO white book on allergy (update
2013) [Internet]. Milwaukee (WI): World Allergy Organization; 2013 [cited 2019 Apr]. Available from:
https://www.worldallergy.org/UserFiles/file/WhiteBook2-2013-v8.pdf.

https://e-aair.org https://doi.org/10.4168/aair.2023.15.5.545 555


Diet Diversity and Allergy

8. Mirabelli MC, Hsu J, Gower WA. Comorbidities of asthma in U.S. children. Respir Med 2016;116:34-40.
PUBMED | CROSSREF
9. Meltzer EO, Blaiss MS, Naclerio RM, Stoloff SW, Derebery MJ, Nelson HS, et al. Burden of allergic rhinitis:
allergies in America, Latin America, and Asia-Pacific adult surveys. Allergy Asthma Proc 2012;33 Suppl
1:S113-41.
PUBMED | CROSSREF
10. Hanifin JM, Reed ML; Eczema Prevalence and Impact Working Group. A population-based survey of
eczema prevalence in the United States. Dermatitis 2007;18:82-91.
PUBMED | CROSSREF
11. Gupta RS, Warren CM, Smith BM, Blumenstock JA, Jiang J, Davis MM, et al. The public health impact of
parent-reported childhood food allergies in the United States. Pediatrics 2018;142:e20181235.
PUBMED | CROSSREF
12. Sampath V, Abrams EM, Adlou B, Akdis C, Akdis M, Brough HA, et al. Food allergy across the globe. J
Allergy Clin Immunol 2021;148:1347-64.
PUBMED | CROSSREF
13. Venter C, Agostoni C, Arshad SH, Ben-Abdallah M, Du Toit G, Flesicher DM, et al. Dietary factors during
pregnancy and atopic outcomes in childhood: a systematic review from the European Academy of Allergy
and Clinical Immunology. Pediatr Allergy Immunol 2020;31:889-912.
PUBMED | CROSSREF
14. Goldring ST, Griffiths CJ, Martineau AR, Robinson S, Yu C, Poulton S, et al. Prenatal vitamin d
supplementation and child respiratory health: a randomised controlled trial. PLoS One 2013;8:e66627.
PUBMED | CROSSREF
15. Litonjua AA, Carey VJ, Laranjo N, Harshfield BJ, McElrath TF, O’Connor GT, et al. Effect of prenatal
supplementation with vitamin D on asthma or recurrent wheezing in offspring by age 3 years: the
VDAART randomized clinical trial. JAMA 2016;315:362-70.
PUBMED | CROSSREF
16. Chawes BL, Bønnelykke K, Stokholm J, Vissing NH, Bjarnadóttir E, Schoos AM, et al. Effect of vitamin D3
supplementation during pregnancy on risk of persistent wheeze in the offspring: a randomized clinical
trial. JAMA 2016;315:353-61.
PUBMED | CROSSREF
17. US Department of Agriculture. Dietary guidelines for Americans: DGA 2020–2025 [Internet].
Washington, D.C.: US Department of Agriculture; 2020 [cited 2021 Jan]. Available from: https://www.
dietaryguidelines.gov/sites/default/files/2020-12/Dietary_Guidelines_for_Americans_2020-2025.pdf.
18. Venter C, Greenhawt M, Meyer RW, Agostoni C, Reese I, du Toit G, et al. EAACI position paper on diet
diversity in pregnancy, infancy and childhood: novel concepts and implications for studies in allergy and
asthma. Allergy 2020;75:497-523.
PUBMED | CROSSREF
19. Venter C, O’Mahony L. Immunonutrition: the importance of a new European Academy of Allergy
and Clinical Immunology working group addressing a significant burden and unmet need. Allergy
2021;76:2303-5.
PUBMED | CROSSREF
20. Venter C, Eyerich S, Sarin T, Klatt KC. Nutrition and the immune system: a complicated tango. Nutrients
2020;12:818.
PUBMED | CROSSREF
21. Venter C, Meyer RW, Nwaru BI, Roduit C, Untersmayr E, Adel-Patient K, et al. EAACI position paper:
influence of dietary fatty acids on asthma, food allergy, and atopic dermatitis. Allergy 2019;74:1429-44.
PUBMED | CROSSREF
22. Venter C, Meyer RW, Greenhawt M, Pali-Schöll I, Nwaru B, Roduit C, et al. Role of dietary fiber in
promoting immune health-An EAACI position paper. Allergy 2022;77:3185-98.
PUBMED | CROSSREF
23. Calder PC. Immunonutrition in surgical and critically ill patients. Br J Nutr 2007;98 Suppl 1:S133-9.
PUBMED | CROSSREF
24. Venter C, Greenhawt M, Meyer RW, Agostoni C, Reese I, du Toit G, et al. EAACI position paper on diet
diversity in pregnancy, infancy and childhood: novel concepts and implications for studies in allergy and
asthma. Allergy 2020;75:497-523.
PUBMED | CROSSREF
25. Ghosh TS, Rampelli S, Jeffery IB, Santoro A, Neto M, Capri M, et al. Mediterranean diet intervention
alters the gut microbiome in older people reducing frailty and improving health status: the NU-AGE 1-year
dietary intervention across five European countries. Gut 2020;69:1218-28.
PUBMED | CROSSREF

https://e-aair.org https://doi.org/10.4168/aair.2023.15.5.545 556


Diet Diversity and Allergy

26. Ruel MT. Is dietary diversity an indicator of food security or dietary quality? A review of measurement
issues and research needs. Food Nutr Bull 2003;24:231-2.
PUBMED | CROSSREF
27. Krebs-Smith SM, Smiciklas-Wright H, Guthrie HA, Krebs-Smith J. The effects of variety in food choices
on dietary quality. J Am Diet Assoc 1987;87:897-903.
PUBMED | CROSSREF
28. Roche ML, Creed-Kanashiro HM, Tuesta I, Kuhnlein HV. Traditional food diversity predicts dietary
quality for the Awajún in the Peruvian Amazon. Public Health Nutr 2008;11:457-65.
PUBMED | CROSSREF
29. Lachat C, Raneri JE, Smith KW, Kolsteren P, Van Damme P, Verzelen K, et al. Dietary species richness as a
measure of food biodiversity and nutritional quality of diets. Proc Natl Acad Sci U S A 2018;115:127-32.
PUBMED | CROSSREF
30. Remans R, Flynn DF, DeClerck F, Diru W, Fanzo J, Gaynor K, et al. Assessing nutritional diversity of
cropping systems in African villages. PLoS One 2011;6:e21235.
PUBMED | CROSSREF
31. Bezerra IN, Sichieri R. Household food diversity and nutritional status among adults in Brazil. Int J Behav
Nutr Phys Act 2011;8:22.
PUBMED | CROSSREF
32. Onyango A, Koski KG, Tucker KL. Food diversity versus breastfeeding choice in determining
anthropometric status in rural Kenyan toddlers. Int J Epidemiol 1998;27:484-9.
PUBMED | CROSSREF
33. Ntwenya JE, Kinabo J, Msuya J, Mamiro P, Mamiro D, Njoghomi E, et al. Rich food biodiversity amid low
consumption of food items in Kilosa district, Tanzania. Food Nutr Bull 2017;38:501-11.
PUBMED | CROSSREF
34. Jones AD. On-farm crop species richness is associated with household diet diversity and quality in
subsistence- and market-oriented farming households in Malawi. J Nutr 2017;147:86-96.
PUBMED | CROSSREF
35. Chomat AM, Solomons NW, Koski KG, Wren HM, Vossenaar M, Scott ME. Quantitative methodologies
reveal a diversity of nutrition, infection/illness, and psychosocial stressors during pregnancy and lactation
in rural Mam-Mayan mother-infant dyads from the Western Highlands of Guatemala. Food Nutr Bull
2015;36:415-40.
PUBMED | CROSSREF
36. Rukundo PM, Andreassen BA, Kikafunda J, Rukooko B, Oshaug A, Iversen PO. Household food insecurity
and diet diversity after the major 2010 landslide disaster in Eastern Uganda: a cross-sectional survey. Br J
Nutr 2016;115:718-29.
PUBMED | CROSSREF
37. Christian AK, Marquis GS, Colecraft EK, Lartey A, Sakyi-Dawson O, Ahunu BK, et al. Caregivers’ nutrition
knowledge and attitudes are associated with household food diversity and children’s animal source food
intake across different agro-ecological zones in Ghana. Br J Nutr 2016;115:351-60.
PUBMED | CROSSREF
38. Ey Chua EY, Zalilah MS, Ys Chin YS, Norhasmah S. Dietary diversity is associated with nutritional status
of Orang Asli children in Krau Wildlife Reserve, Pahang. Malays J Nutr 2012;18:1-13.
PUBMED
39. Wright MJ, Bentley ME, Mendez MA, Adair LS. The interactive association of dietary diversity scores and
breast-feeding status with weight and length in Filipino infants aged 6-24 months. Public Health Nutr
2015;18:1762-73.
PUBMED | CROSSREF
40. Woo JG, Herbers PM, McMahon RJ, Davidson BS, Ruiz-Palacios GM, Peng YM, et al. Longitudinal
development of infant complementary diet diversity in 3 international cohorts. J Pediatr 2015;167:969-
974.e1.
PUBMED | CROSSREF
41. Chandrasekhar S, Aguayo VM, Krishna V, Nair R. Household food insecurity and children’s dietary
diversity and nutrition in India. Evidence from the comprehensive nutrition survey in Maharashtra.
Matern Child Nutr 2017;13 Suppl 2:e12447.
PUBMED | CROSSREF
42. Agize A, Jara D, Dejenu G. Level of knowledge and practice of mothers on minimum dietary diversity
practices and associated factors for 6-23-month-old children in Adea Woreda, Oromia, Ethiopia. Biomed
Res Int 2017;2017:7204562.
PUBMED | CROSSREF

https://e-aair.org https://doi.org/10.4168/aair.2023.15.5.545 557


Diet Diversity and Allergy

43. Gewa CA, Murphy SP, Weiss RE, Neumann CG. Determining minimum food intake amounts for diet
diversity scores to maximize associations with nutrient adequacy: an analysis of schoolchildren’s diets in
rural Kenya. Public Health Nutr 2014;17:2667-73.
PUBMED | CROSSREF
44. Shamim AA, Mashreky SR, Ferdous T, Tegenfeldt K, Roy S, Rahman AK, et al. Pregnant women diet quality
and its sociodemographic determinants in southwestern Bangladesh. Food Nutr Bull 2016;37:14-26.
PUBMED | CROSSREF
45. Leroy JL, Razak AA, Habicht JP. Only children of the head of household benefit from increased household
food diversity in northern Ghana. J Nutr 2008;138:2258-63.
PUBMED | CROSSREF
46. Msaki MM, Hendriks SL. Do food quality and food quantity talk the same? Lesson from household food
security study in Embo, South Africa. J Am Coll Nutr 2013;32:165-76.
PUBMED | CROSSREF
47. Hatløy A, Torheim LE, Oshaug A. Food variety--a good indicator of nutritional adequacy of the diet? A
case study from an urban area in Mali, West Africa. Eur J Clin Nutr 1998;52:891-8.
PUBMED | CROSSREF
48. Mok E, Vanstone CA, Gallo S, Li P, Constantin E, Weiler HA. Diet diversity, growth and adiposity in
healthy breastfed infants fed homemade complementary foods. Int J Obes 2017;41:776-82.
PUBMED | CROSSREF
49. Conklin AI, Monsivais P, Khaw KT, Wareham NJ, Forouhi NG. Dietary diversity, diet cost, and incidence
of type 2 diabetes in the United Kingdom: a prospective cohort study. PLoS Med 2016;13:e1002085.
PUBMED | CROSSREF
50. Isa F, Xie LP, Hu Z, Zhong Z, Hemelt M, Reulen RC, et al. Dietary consumption and diet diversity and risk
of developing bladder cancer: results from the South and East China case-control study. Cancer Causes
Control 2013;24:885-95.
PUBMED | CROSSREF
51. Hatløy A, Hallund J, Diarra MM, Oshaug A. Food variety, socioeconomic status and nutritional status in
urban and rural areas in Koutiala (Mali). Public Health Nutr 2000;3:57-65.
PUBMED | CROSSREF
52. Motbainor A, Worku A, Kumie A. Stunting Is associated with food diversity while wasting with food
insecurity among underfive children in East and West Gojjam zones of Amhara region, Ethiopia. PLoS
One 2015;10:e0133542.
PUBMED | CROSSREF
53. Venter C, Maslin K, Holloway JW, Silveira LJ, Fleischer DM, Dean T, et al. Different measures of diet
diversity during infancy and the association with childhood food allergy in a UK birth cohort study. J
Allergy Clin Immunol Pract 2020;8:2017-26.
PUBMED | CROSSREF
54. Vadiveloo M, Dixon LB, Mijanovich T, Elbel B, Parekh N. Development and evaluation of the US Healthy
Food Diversity index. Br J Nutr 2014;112:1562-74.
PUBMED | CROSSREF
55. Sullivan ZA, Khoury-Hanold W, Lim J, Smillie C, Biton M, Reis BS, et al. γδ T cells regulate the intestinal
response to nutrient sensing. Science 2021;371:eaba8310.
PUBMED | CROSSREF
56. Leeming ER, Johnson AJ, Spector TD, Le Roy CI. Effect of diet on the gut microbiota: rethinking
intervention duration. Nutrients 2019;11:2862.
PUBMED | CROSSREF
57. Xiao C, Wang JT, Su C, Miao Z, Tang J, Ouyang Y, et al. Associations of dietary diversity with the gut
microbiome, fecal metabolites, and host metabolism: results from 2 prospective Chinese cohorts. Am J
Clin Nutr 2022;116:1049-58.
PUBMED | CROSSREF
58. Cotillard A, Cartier-Meheust A, Litwin NS, Chaumont S, Saccareau M, Lejzerowicz F, et al. A posteriori
dietary patterns better explain variations of the gut microbiome than individual markers in the American
Gut Project. Am J Clin Nutr 2022;115:432-43.
PUBMED | CROSSREF
59. Amamoto R, Shimamoto K, Suwa T, Park S, Matsumoto H, Shimizu K, et al. Relationships between
dietary diversity and gut microbial diversity in the elderly. Benef Microbes 2022;13:453-64.
PUBMED | CROSSREF
60. Claesson MJ, Jeffery IB, Conde S, Power SE, O’Connor EM, Cusack S, et al. Gut microbiota composition
correlates with diet and health in the elderly. Nature 2012;488:178-84.
PUBMED | CROSSREF

https://e-aair.org https://doi.org/10.4168/aair.2023.15.5.545 558


Diet Diversity and Allergy

61. Bäckhed F, Roswall J, Peng Y, Feng Q, Jia H, Kovatcheva-Datchary P, et al. Dynamics and stabilization of
the human gut microbiome during the first year of life. Cell Host Microbe 2015;17:690-703.
PUBMED | CROSSREF
62. Homann CM, Rossel CA, Dizzell S, Bervoets L, Simioni J, Li J, et al. Infants’ first solid foods: impact on
gut microbiota development in two intercontinental cohorts. Nutrients 2021;13:2639.
PUBMED | CROSSREF
63. Laursen MF, Andersen LB, Michaelsen KF, Mølgaard C, Trolle E, Bahl MI, et al. Infant gut microbiota
development is driven by transition to family foods independent of maternal obesity. mSphere
2016;1:e00069-15.
PUBMED | CROSSREF
64. Roduit C, Frei R, Ferstl R, Loeliger S, Westermann P, Rhyner C, et al. High levels of butyrate and
propionate in early life are associated with protection against atopy. Allergy 2019;74:799-809.
PUBMED | CROSSREF
65. Tan J, McKenzie C, Vuillermin PJ, Goverse G, Vinuesa CG, Mebius RE, et al. Dietary fiber and bacterial
SCFA enhance oral tolerance and protect against food allergy through diverse cellular pathways. Cell Rep
2016;15:2809-24.
PUBMED | CROSSREF
66. Berni Canani R, De Filippis F, Nocerino R, Laiola M, Paparo L, Calignano A, et al. Specific signatures
of the gut microbiota and increased levels of butyrate in children treated with fermented cow’s milk
containing heat-killed Lactobacillus paracasei CBA L74. Appl Environ Microbiol 2017;83:e01206-17.
PUBMED | CROSSREF
67. Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, et al. Metabolites produced by
commensal bacteria promote peripheral regulatory T-cell generation. Nature 2013;504:451-5.
PUBMED | CROSSREF
68. Furusawa Y, Obata Y, Hase K. Commensal microbiota regulates T cell fate decision in the gut. Semin
Immunopathol 2015;37:17-25.
PUBMED | CROSSREF
69. Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly-Y M, et al. The microbial
metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 2013;341:569-73.
PUBMED | CROSSREF
70. Peng L, Li ZR, Green RS, Holzman IR, Lin J. Butyrate enhances the intestinal barrier by facilitating
tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J Nutr
2009;139:1619-25.
PUBMED | CROSSREF
71. Lee BR, Jung HI, Kim SK, Kwon M, Kim H, Jung M, et al. Dietary diversity during early infancy increases
microbial diversity and prevents egg allergy in high-risk infants. Immune Netw 2021;22:e17.
PUBMED | CROSSREF
72. Marrs T, Jo JH, Perkin MR, Rivett DW, Witney AA, Bruce KD, et al. Gut microbiota development during
infancy: Impact of introducing allergenic foods. J Allergy Clin Immunol 2021;147:613-621.e9.
PUBMED | CROSSREF
73. Akdis CA. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other
chronic conditions? Nat Rev Immunol 2021;21:739-51.
PUBMED | CROSSREF
74. Chassaing B, Koren O, Goodrich JK, Poole AC, Srinivasan S, Ley RE, et al. Dietary emulsifiers impact the
mouse gut microbiota promoting colitis and metabolic syndrome. Nature 2015;519:92-6.
PUBMED | CROSSREF
75. Jiang Z, Zhao M, Zhang H, Li Y, Liu M, Feng F. Antimicrobial emulsifier-glycerol monolaurate induces
metabolic syndrome, gut microbiota dysbiosis, and systemic low-grade inflammation in low-fat diet fed
mice. Mol Nutr Food Res 2018;62:1700547.
PUBMED | CROSSREF
76. Atzeni A, Martínez MÁ, Babio N, Konstanti P, Tinahones FJ, Vioque J, et al. Association between
ultra-processed food consumption and gut microbiota in senior subjects with overweight/obesity and
metabolic syndrome. Front Nutr 2022;9:976547.
PUBMED | CROSSREF
77. Roh Y, Lee J, Kim WG, Yi G, Kim BK, Oh B. Effect of diet change on gut microbiota: observational pilot
study of four urban couples. J Obes Metab Syndr 2017;26:257-65.
PUBMED | CROSSREF
78. Knight T, Smith PK, Soutter V, Oswald E, Venter C. Is the low pH of infant and toddler foods a concern?
Pediatr Allergy Immunol 2021;32:1103-6.
PUBMED | CROSSREF

https://e-aair.org https://doi.org/10.4168/aair.2023.15.5.545 559


Diet Diversity and Allergy

79. Maslin K, Venter C. Nutritional aspects of commercially prepared infant foods in developed countries: a
narrative review. Nutr Res Rev 2017;30:138-48.
PUBMED | CROSSREF
80. Moumin NA, Green TJ, Golley RK, Netting MJ. Are the nutrient and textural properties of Australian
commercial infant and toddler foods consistent with infant feeding advice? Br J Nutr 2020;124:754-60.
PUBMED | CROSSREF
81. Netting MJ, Gold MS, Palmer DJ. Low allergen content of commercial baby foods. J Paediatr Child Health
2020;56:1613-7.
PUBMED | CROSSREF
82. Venter C, Palumbo MP, Glueck DH, Sauder KA, Perng W, O’Mahony L, et al. Comparing the diagnostic
accuracy of measures of maternal diet during pregnancy for offspring allergy outcomes: the healthy start
study. J Allergy Clin Immunol Pract 2023;11:255-263.e1.
PUBMED | CROSSREF
83. Roduit C, Frei R, Depner M, Schaub B, Loss G, Genuneit J, et al. Increased food diversity in the first year
of life is inversely associated with allergic diseases. J Allergy Clin Immunol 2014;133:1056-64.
PUBMED | CROSSREF
84. Nwaru BI, Takkinen HM, Niemelä O, Kaila M, Erkkola M, Ahonen S, et al. Introduction of complementary
foods in infancy and atopic sensitization at the age of 5 years: timing and food diversity in a Finnish birth
cohort. Allergy 2013;68:507-16.
PUBMED | CROSSREF
85. Nwaru BI, Takkinen HM, Kaila M, Erkkola M, Ahonen S, Pekkanen J, et al. Food diversity in infancy and
the risk of childhood asthma and allergies. J Allergy Clin Immunol 2014;133:1084-91.
PUBMED | CROSSREF
86. Maslin K, Pickett K, Ngo S, Anderson W, Dean T, Venter C. Dietary diversity during infancy and the
association with childhood food allergen sensitization. Pediatr Allergy Immunol 2022;33:e13650.
PUBMED | CROSSREF
87. Zhong C, Guo J, Tan T, Wang H, Lin L, Gao D, et al. Increased food diversity in the first year of life is
inversely associated with allergic outcomes in the second year. Pediatr Allergy Immunol 2022;33:e13707.
PUBMED | CROSSREF
88. Markevych I, Standl M, Lehmann I, von Berg A, Heinrich J. Food diversity during the first year of life and
allergic diseases until 15 years. J Allergy Clin Immunol 2017;140:1751-1754.e4.
PUBMED | CROSSREF
89. Sausenthaler S, Heinrich J, Koletzko S; GINIplus and LISAplus Study Groups. Early diet and the risk of
allergy: what can we learn from the prospective birth cohort studies GINIplus and LISAplus? Am J Clin
Nutr 2011;94:2012S-7S.
PUBMED | CROSSREF
90. Zutavern A, Brockow I, Schaaf B, von Berg A, Diez U, Borte M, et al. Timing of solid food introduction
in relation to eczema, asthma, allergic rhinitis, and food and inhalant sensitization at the age of 6 years:
results from the prospective birth cohort study LISA. Pediatrics 2008;121:e44-52.
PUBMED | CROSSREF
91. Zutavern A, Brockow I, Schaaf B, Bolte G, von Berg A, Diez U, et al. Timing of solid food introduction
in relation to atopic dermatitis and atopic sensitization: results from a prospective birth cohort study.
Pediatrics 2006;117:401-11.
PUBMED | CROSSREF
92. Turati F, Bertuccio P, Galeone C, Pelucchi C, Naldi L, Bach JF, et al. Early weaning is beneficial to prevent
atopic dermatitis occurrence in young children. Allergy 2016;71:878-88.
PUBMED | CROSSREF
93. Fergusson DM, Horwood LJ, Shannon FT. Risk factors in childhood eczema. J Epidemiol Community
Health 1982;36:118-22.
PUBMED | CROSSREF
94. Fergusson DM, Horwood LJ, Shannon FT. Early solid feeding and recurrent childhood eczema: a 10-year
longitudinal study. Pediatrics 1990;86:541-6.
PUBMED | CROSSREF
95. Fergusson DM, Horwood LJ, Beautrais AL, Shannon FT, Taylor B. Eczema and infant diet. Clin Allergy
1981;11:325-31.
PUBMED | CROSSREF
96. Fergusson DM, Horwood LJ. Early solid food diet and eczema in childhood: a 10-year longitudinal study.
Pediatr Allergy Immunol 1994;5:44-7.
PUBMED | CROSSREF

https://e-aair.org https://doi.org/10.4168/aair.2023.15.5.545 560


Diet Diversity and Allergy

97. Stampfli M, Frei R, Divaret-Chauveau A, Schmausser-Hechfellner E, Karvonen AM, Pekkanen J, et al.


Inverse associations between food diversity in the second year of life and allergic diseases. Ann Allergy
Asthma Immunol 2022;128:39-45.
PUBMED | CROSSREF
98. Perkin MR, Logan K, Tseng A, Raji B, Ayis S, Peacock J, et al. Randomized trial of introduction of
allergenic foods in breast-fed infants. N Engl J Med 2016;374:1733-43.
PUBMED | CROSSREF
99. Quake AZ, Liu TA, D’Souza R, Jackson KG, Woch M, Tetteh A, et al. Early introduction of multi-allergen
mixture for prevention of food allergy: pilot study. Nutrients 2022;14:737.
PUBMED | CROSSREF
100. Roduit C, Frei R, Loss G, Büchele G, Weber J, Depner M, et al. Development of atopic dermatitis according
to age of onset and association with early-life exposures. J Allergy Clin Immunol 2012;130:130-136.e5.
PUBMED | CROSSREF

https://e-aair.org https://doi.org/10.4168/aair.2023.15.5.545 561

You might also like