Revisiting the hygiene hypothesis for allergy and asthma

doi:10.1016/j.jaci.2015.08.012

Journal of Allergy and Clinical Immunology

Volume 136, Issue 4, October 2015, Pages 860-865

https://doi.org/10.1016/j.jaci.2015.08.012 Get rights and content

The hygiene hypothesis, which describes the protective influence of microbial exposures in early life on the development of allergy and asthma, has continued its swell of academic interest, investigation, and evolution. This article is focused on studies published in the past 3 years that have furthered the substance and shape of hygiene theory, primarily as it relates to allergic airways and asthma. Recent investigations have furthered an overarching “microbiome hypothesis” to home features, medical practices, and cleanliness behaviors that are suspects in the hygiene effect. Relatively crude markers of the protective microbial environment have been supplanted by culture-independent microbiome science, distinguishing the characteristics of potentially protective microbiomes from pathologic features. Understanding how the microbiome is shaped and affects healthful versus harmful outcomes in the human host is relatively nascent. Good clues are emerging that give mechanistic substance to the theory and could help guide microbe-based therapeutics to fill the allergy and asthma management gap in prevention and disease modification.

Section snippets

The Amish in America: A case study

Life on rural European farms has been a rich resource of naturally occurring evidence that microbial exposures from proximal living with domestic animals beginning in early life might protect against the development of allergies and asthma.3, 4 This has provided a compelling body of evidence in support of hygiene theory. Could these farming ways indicate environments and lifestyles that are allergy and asthma protective today and were even more so in earlier times before the global increase in

Clean (and not so clean) living

Recent investigations have shed light on personal hygiene behaviors suspected of contributing to the hygiene effect. In a German longitudinal birth cohort study, personal cleanliness (eg, hand washing and showering) was associated with lower levels of endotoxin (ie, a bacterial marker) and muramic acid (ie, a fungal marker) in bedding and floor dust.⁶ In comparison, household cleanliness (eg, cleaning floors and bathrooms, dusting, and changing towels) was associated with less dust but not with

Substantiating protective home environments

Recent studies have substantiated prior observations attributed to hygiene theory. David Strachan, who first demonstrated the relationship of increased sibship with less atopy, extended these associations on a global scale in the International Study of Asthma and Allergies in Childhood cohort.⁹ Globally, increasing numbers of siblings, especially older siblings, were negatively associated with hay fever and eczema. These associations were stronger in more affluent countries, which is consistent

The paradox of US inner cities

Because there is a high burden of severe asthma in US inner cities, the National Institutes of Health/National Institute of Allergy and Infectious Diseases has sponsored an inner-city birth cohort study, Urban Environment and Childhood Asthma (URECA), to understand how US inner cities foster severe asthma development.¹⁷ From a hygiene hypothesis perspective, inner-city environments could be suspected of being protective on allergy and asthma development, which is a paradox. Although this study

Microbiome theory of allergy and asthma prevention

The microbiome has been avidly investigated as the root of the hygiene hypothesis and possibly the common thread linking the many epidemiologic observations. Microbiome investigation has taken on new depth, in part because of extraordinary advances in the scope of microbiome characterization using new culture-independent genomic methods. The findings of new microbiome science applied to allergy and asthma has been the subject of several excellent recent reviews.16, 28, 29, 30 Although the

Conclusions

Translating hygiene/microbiome theory to microbe-based therapeutics has been considered often.65, 66 Effective translation to help address the unmet need of allergy and asthma prevention in human health has been elusive. Compelling scientific leads have been followed in randomized clinical trials without significant benefit for patients and doctors in airways allergy and asthma clinics. For example, regarding probiotic supplementation, a recent systematic review and meta-analysis of 17

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The composition of the gut microbiome has been associated with development of atopic conditions such as food allergy (FA) and asthma. African American or Black children with FA have higher rate of asthma compared to their White counterparts.
We sought to investigate whether the diversity and relative abundance (RA) of gut microbiota is different between children with FA from different racial backgrounds living in the same cities. Furthermore, we aimed to understand whether the difference in the gut microbiota is associated with asthma in children with FA.
We analyzed and compared the stool microbiome of a cohort of Black and White children with FA by shotgun genomic sequencing.
A total of 152 children with IgE-mediated FA enrolled onto FORWARD (Food Allergy Outcomes Related to White and African American Racial Differences); 30 Black and 122 White children were included. The RA of several bacteria was associated with race and asthma. Most notably the RA of Bacteroides thetaiotaomicron, Chlamydia thrachomatis, Parabacteroides goldsteinii, and Bacteroides eggerthii were significantly higher, while the RA of Bifidobacterium sp CAG:754, Parabacterium johnsonii, Bacteroides intestinalis, and Bifidobacterium breve were significantly lower in stool samples of Black children compared to White children. Asthma was associated with lower RA of B breve, Bifidobacterium catenulatum, Prevotella copri, Veilloella sp CAG:933, and Bacteroides plebius, and higher RA of 3 Bacteroides species.
The observed variations in the gut microbiota of Black and White children such as differences in the Bacteroides and Bifidobacterium species along with their association to history of asthma in our cohort is indicative of their potential role in the higher rate of asthma observed among Black children with FA.
Early-immune development in asthma: A review of the literature
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This review presents a comprehensive examination of the various factors contributing to the immunopathogenesis of asthma from the prenatal to preschool period. We focus on the contributions of genetic and environmental components as well as the role of the nasal and gut microbiome on immune development. Predisposing genetic factors, including inherited genes associated with increased susceptibility to asthma, are discussed alongside environmental factors such as respiratory viruses and pollutant exposure, which can trigger or exacerbate asthma symptoms. Furthermore, the intricate interplay between the nasal and gut microbiome and the immune system is explored, emphasizing their influence on allergic immune development and response to environmental stimuli. This body of literature underscores the necessity of a comprehensive approach to comprehend and manage asthma, as it emphasizes the interactions of multiple factors in immune development and disease progression.
Birth mode is associated with development of atopic dermatitis in infancy and early childhood
2023, Journal of Allergy and Clinical Immunology: Global
Birth by caesarean section (CS) is associated with development of allergic diseases, but its role in the development of atopic dermatitis (AD) is less convincing.
Our primary aim was to determine if birth mode was associated with AD in 3-year-olds and secondarily to determine if birth mode was associated with early onset and/or persistent AD in the first 3 years of life.
We included 2129 mother–child pairs from the Scandinavian population-based prospective PreventADALL cohort with information on birth mode including vaginal birth, either traditional (81.3%) or in water (4.0%), and CS before (6.3%) and after (8.5%) onset of labor. We defined early onset AD as eczema at 3 months and AD diagnosis by 3 years of age. Persistent AD was defined as eczema both in the first year and at 3 years of age, together with an AD diagnosis by 3 years of age.
AD was diagnosed at 3, 6, 12, 24, and/or 36 months in 531 children (25%). Compared to vaginal delivery, CS was overall associated with increased odds of AD by 3 years of age, with adjusted odds ratio (95% confidence interval) of 1.33 (1.02-1.74), and higher odds of early onset AD (1.63, 1.06-2.48). The highest odds for early onset AD were observed in infants born by CS after onset of labor (1.83, 1.09-3.07). Birth mode was not associated with persistent AD.
CS was associated with increased odds of AD by 3 years of age, particularly in infants presenting with eczema at 3 months of age.
Trends (2007–2019) of major atopic diseases throughout the life span in a large Mexican population
2023, World Allergy Organization Journal
Major atopic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), and asthma share the same atopic background, but they often show differences in their epidemiological behavior.
We aimed to report the profile of these atopic diseases in a large Mexican population, including their age-related incidences, male:female (M:F) ratios, recent time trends, and association with altitude.
Registries from the largest, nationwide health institution in Mexico (more than 34 million insured subjects), were reviewed. New cases of AD, AR, and asthma diagnosed each year by family physicians from 2007 to 2019 were adjusted by the corresponding insured population to estimate incidence rates.
Incidences of the 3 atopic diseases were highest in the 0–4 years age-group and progressively decreased thereafter until adolescence. Asthma and AR, but not AD, were more frequent in males during childhood (M:F ratios of 1.5, 1.3, and 0.95, respectively), but predominated in females during adulthood (M:F ratios of 0.52, 0.68, and 0.73, respectively). Time trends showed an initial increasing trend of annual incidences, with a peak around 2009–2011, and a downward trend afterward. This decreasing trend was seen in all age-groups and was more evident for AD (∼50% drop) and asthma (∼40% drop) than for AR (∼20% drop). Geographical distribution suggested that incidences of asthma and AR, but not of AD, had an inverse association with altitude.
Annual incidences of the 3 major atopic diseases have declined in recent years in almost all age groups, and their epidemiological profile during the life span showed contrasting differences according to age, sex, and ecological association with altitude, mainly regarding AD.
Interplay between natural environment, human microbiota and immune system: A scoping review of interventions and future perspectives towards allergy prevention
2022, Science of the Total Environment
Urbanization and biodiversity loss are linked to chronic disorders, in particular allergic diseases. The aim of this scoping review was to provide a synopsis of intervention studies specifically examining the influence of exposure to natural environments on human microbiota as well as immunological markers as suggested interlink between natural environment and the development of allergic diseases.
We searched PubMed (MEDLINE®) and all references cited in the included studies following the PRISMA statement guidelines. No restrictions regarding age and sex of study participants, language or publication date were made. The protocol was registered at OSF REGISTRIES (https://osf.io/musgr).
After screening, eight intervention studies were included. The interventions reported were mainly of pilot character and various, ranging from nature-related educational programs, biodiversity interventions in day-cares to short-term contact with soil- and sand-preparations. Most of the studied interventions appeared to increase human microbiota richness and diversity in specific taxa groups in the short-time. Immunological markers were assessed in only two studies. In these, their associations with human microbiota richness were pre-dominantly reported. Conclusion: There is some evidence that the so-called biodiversity interventions have the potential to diversify human microbiota, at least over a short period. Adequately powered randomized controlled trials with long term follow-up are required to examine sustainable effects on microbiota and immune system.
Longitudinal atopic dermatitis endotypes: An atopic march paradigm that includes Black children
2022, Journal of Allergy and Clinical Immunology
The atopic march has been studied mostly in White populations, biasing our current paradigms.
We sought to define the atopic march in Black and White children and explore mechanisms for racial differences.
Utilizing the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH) cohort (n = 601), we assessed longitudinal sensitization, food allergy (FA), allergic rhinitis, risk of asthma development (through the Pediatric Asthma Risk Score), Scoring for Atopic Dermatitis (SCORAD), transepidermal water loss, skin filaggrin (FLG) expression, exposures, and genetic heritability to define AD progression endotypes in Black and White children.
White MPAACH children were more likely to be sensitized to aero and food allergens (P = .0001) and over 3 times more likely to develop FA and/or allergic rhinitis (AR) without asthma risk (P < .0001). In contrast, Black children were over 6 times more likely to proceed to high asthma risk without FA, sensitization, or AR (P < .0001). White children had higher lesional and nonlesional transepidermal water loss (both P < .001) as well as decreased nonlesional keratinocyte FLG expression (P = .02). Black children had increased genetic heritability for asthma risk and higher rates of exposures to secondhand smoke and traffic-related air pollution.
Black and White children with AD have distinct allergic trajectories defined by different longitudinal endotypes. Black children exhibit higher asthma risk despite a more intact skin barrier and less sensitization, FA, and AR. White children have less asthma risk, despite a more dysfunctional skin barrier, and more FA, AR, and sensitization. The observed racial differences are likely due in part to increased genetic heritability for asthma risk and harmful environmental exposures in Black children. Collectively, our findings provide a new paradigm for an atopic march that is inclusive of Black children.

View all citing articles on Scopus

: Disclosure of potential conflict of interest: A. H. Liu is on the Data Safety Monitoring Committee for GlaxoSmithKline and has received payment for lectures from Merck.

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Reviews and feature articleRevisiting the hygiene hypothesis for allergy and asthma

Section snippets

The Amish in America: A case study

Clean (and not so clean) living

Substantiating protective home environments

The paradox of US inner cities

Microbiome theory of allergy and asthma prevention

Conclusions

J Allergy Clin Immunol

J Allergy Clin Immunol

Environ Pollut

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Invest Dermatol

J Allergy Clin Immunol

J Allergy Clin Immunol

Cell Host Microbe

Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Cell

Cell

J Allergy Clin Immunol

J Allergy Clin Immunol

J Biol Chem

J Allergy Clin Immunol

Contemp Clin Trials

Hygiene hypothesis for allergy and asthma

Experimental researches on the causes and nature of catarrhus aestivus (hay-fever or hay-asthma)

Environmental exposure to endotoxin and its relation to asthma in school-age children

N Engl J Med

Exposure to environmental microorganisms and childhood asthma

N Engl J Med

Asthma and the hygiene hypothesis. Does cleanliness matter?

Am J Respir Crit Care Med

Allergy in children in hand versus machine dishwashing

Pediatrics

Pacifier cleaning practices and risk of allergy development

Pediatrics

Siblings, asthma, rhinoconjunctivitis and eczema: a worldwide perspective from the International Study of Asthma and Allergies in Childhood

Clin Exp Allergy

Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section

Gut

Endotoxin exposure is a risk factor for asthma: the national survey of endotoxin in United States housing

Am J Respir Crit Care Med

Indoor pollutant exposures modify the effect of airborne endotoxin on asthma in urban children

Am J Respir Crit Care Med

The human microbiome. Early life determinant of health outcomes

Ann Am Thorac Soc

The Urban Environment and Childhood Asthma (URECA) birth cohort study: design, methods, and study population

BMC Pulm Med

Exposure to dogs and cats in the first year of life and risk of allergic sensitization at 6 to 7 years of age

JAMA

Effects of dog ownership in early childhood on immune development and atopic diseases

Clin Exp Allergy

Man's best friend? The effect of pet ownership on house dust microbial communities

J Allergy Clin Immunol

Reviews and feature article
Revisiting the hygiene hypothesis for allergy and asthma