The microbiome in allergic disease: Current understanding and future opportunities—2017 PRACTALL document of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology

doi:10.1016/j.jaci.2017.02.007

Journal of Allergy and Clinical Immunology

Volume 139, Issue 4, April 2017, Pages 1099-1110

https://doi.org/10.1016/j.jaci.2017.02.007 Get rights and content

PRACTALL is a joint initiative of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology to provide shared evidence-based recommendations on cutting-edge topics in the field of allergy and immunology. PRACTALL 2017 is focused on what has been established regarding the role of the microbiome in patients with asthma, atopic dermatitis, and food allergy. This is complemented by outlining important knowledge gaps regarding its role in allergic disease and delineating strategies necessary to fill these gaps. In addition, a review of progress in approaches used to manipulate the microbiome will be addressed, identifying what has and has not worked to serve as a baseline for future directions to intervene in allergic disease development, progression, or both.

Section snippets

Microbial ecology

Trillions of microbes colonize the skin and mucosal body surfaces. These microbes are highly adapted to survive within complex community structures, requiring nutrients from other microbes, host processes, or both (Fig 1). Many bacterial species within these communities lack genes that are essential for bacterial fitness in other environments, whereas they possess genes that benefit the host with little or no benefit to the bacterium, suggesting a symbiotic coevolution of bacterial communities

Assessment of the microbiota

Classically, microbiota composition and diversity were assessed with tools, such as microscopy and in vitro culture. More recently developed culture-independent approaches targeting small subunit (16S) rRNA gene sequences or metagenomic shotgun sequencing have allowed for unprecedented detailed assessments of the diversity, composition, and function of many microbial ecosystems.¹⁷ However, comparative analysis between different studies has been problematic because of differences in phenotyping,

Asthma

Significant advances have been made in our understanding of the genetic, environmental, and immunologic factors that shape asthma. However, asthma is clinically heterogeneous, and underlying causes for many phenotypes remain poorly understood.24, 25, 26, 27, 28 Microbes have long been postulated to play a role in asthma and might also shape its heterogeneity.29, 30 These roles include the following contexts: (1) the effect of early-life exposure to microbially rich environments on

AD is a complex familial transmitted skin disease with distinct phenotypes and endotypes.⁶⁵ Two major biologic pathways are responsible for AD: epidermal epithelial dysfunction and altered innate/adaptive immune responses.66, 67 The increased prevalence of AD, particularly in industrialized regions, has been hypothesized to be due to excessive hygiene accompanying the Western lifestyle reducing exposure of the host's immune system to education provided by beneficial microbes. A subset of

Food allergy

Food allergy is thought to involve deviation from the default state of mucosal immune tolerance that can be driven by diet, commensal microbiota, and the interactions between them.⁸⁶ Studies of the gut microbiota in patients with food allergy have yielded variable findings on bacteria associated with the condition. Heterogeneity in diagnostic criteria, variable food allergy subphenotypes (eg, allergy to different foods), altered diet, and differences in profiling and analytic approaches

Strategies to manipulate the microbiome

Probiotic and prebiotic trials in patients with food allergy, AD, and asthma represent attempts to deliberately modify microbiota and their metabolism.¹⁰¹ Probiotics can be defined as live microorganisms that, when administered in adequate amounts, have the potential to confer a health benefit on the host. Notably, the definition of a probiotic does not differentiate between the wide range of potential health benefits, and it is clear that not all probiotics will influence the immune system in

Analytics

One limitation associated with many current studies is that they focus exclusively on the bacterial microbiota and omit the likely important contribution of the mycobiome and virome. Approaches to characterize the mycobiome composition are developing but still difficult. In particular, isolation of fungal DNA requires specific processing that is typically not used in classical bacterial microbiota analysis. In addition, fungal sequence databases, which allow the DNA sequence fragments to be

Conclusion

Because asthma, AD, and food allergy are complex and heterogeneous diseases, it is unlikely that the microbiota implicated in these diseases or even the microbiome in its entirety can fully capture the interdependent dynamics of the molecular networks involved in these diseases (Fig 2). Our understanding of allergic diseases has been advanced not only by studies of the microbiome but also by data generated through genome-wide association, transcriptomic, epigenomic, and metabolomic studies.¹¹⁰

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Analytical challenges in omics research on asthma and allergy: A National Institute of Allergy and Infectious Diseases workshop
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Studies of asthma and allergy are generating increasing volumes of omics data for analysis and interpretation. The National Institute of Allergy and Infectious Diseases (NIAID) assembled a workshop comprising investigators studying asthma and allergic diseases using omics approaches, omics investigators from outside the field, and NIAID medical and scientific officers to discuss the following areas in asthma and allergy research: genomics, epigenomics, transcriptomics, microbiomics, metabolomics, proteomics, lipidomics, integrative omics, systems biology, and causal inference. Current states of the art, present challenges, novel and emerging strategies, and priorities for progress were presented and discussed for each area. This workshop report summarizes the major points and conclusions from this NIAID workshop. As a group, the investigators underscored the imperatives for rigorous analytic frameworks, integration of different omics data types, cross-disciplinary interaction, strategies for overcoming current limitations, and the overarching goal to improve scientific understanding and care of asthma and allergic diseases.
Atopic dermatitis: Pathophysiology, microbiota, and metabolome – A comprehensive review
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Atopic dermatitis (AD) is a prevalent inflammatory skin condition that commonly occurs in children. Genetics, environment, and defects in the skin barrier are only a few of the factors that influence how the disease develops. As human microbiota research has advanced, more scientific evidence has shown the critical involvement of the gut and skin bacteria in the pathogenesis of atopic dermatitis. Microbiome dysbiosis, defined by changed diversity and composition, as well as the development of pathobionts, has been identified as a potential cause for recurring episodes of atopic dermatitis. Gut dysbiosis causes "leaky gut syndrome" by disrupting the epithelial lining of the gut, which allows bacteria and other endotoxins to enter the bloodstream and cause inflammation. The same is true for the disruption of cutaneous homeostasis caused by skin dysbiosis, which enables bacteria and other pathogens to reach deeper skin layers or even systemic circulation, resulting in inflammation. Furthermore, it is now recognized that the gut and skin microbiota releases both beneficial and toxic metabolites. Here, this review covers a range of topics related to AD, including its pathophysiology, the microbiota-AD connection, commonly used treatments, and the significance of metabolomics in AD prevention, treatment, and management, recognizing its potential in providing valuable insights into the disease.
Global knowledge mapping and emerging research trends in the microbiome and asthma: A bibliometric and visualized analysis using VOSviewer and CiteSpace
2024, Heliyon
Numerous prior studies have extensively highlighted the significance of the microbiome in association with asthma. While several studies have concentrated on the asthma microbiome in previous research, there is currently a lack of publications that employ bibliometric methods to assess this area.
In this study, the Web of Science Core Collection database was utilized as the data source, and the SCI-EXPANDED index was employed to ensure that the retrieved data were comprehensive and accurate. All original research articles and review articles related to the correlation between asthma and the microbiome were systematically searched from the inception of the database until June 20, 2023. These articles were subsequently visualized and analyzed using VOSviewer and CiteSpace software.
A total of 1366 relevant publications were acquired, indicating a consistent annual increase in global publications in the field. The United States and China emerged as the top two contributors to international publications. Among prolific authors, Susan V. Lynch achieved the highest publication record, with Hans Bisgaard and Jakob Stokholm sharing the second position. The majority of publications concentrated on allergy-related and microbiome areas, with a few comprehensive journals standing out. Journals with 40 or more publications included the Journal of Allergy and Clinical Immunology, Allergy, Frontiers in Immunology, and PLOS One. The top 5 cited journals were the Journal of Allergy and Clinical Immunology, PLOS One, American Journal of Respiratory and Critical Care Medicine, Clinical and Experimental Allergy, and Nature. Upon analyzing keywords, high-frequency terms, such as asthma, gut microbiota, microbiome, children, childhood asthma, allergy, risk, exposure, inflammation, diversity, and chain fatty acids emerged as representative terms in the field.
This study systematically presented a comprehensive overview of the literature regarding the association between asthma and the microbiome over the last two decades. Through a bibliometric perspective, the findings may assist researchers with a better understanding of the essential information in the field.
Green tea polyphenols alleviate β-conglycinin-induced anaphylaxis by modulating gut microbiota in rats
2023, Food Bioscience
Heretofore, there are no effective therapeutic interventions for food allergies induced by β-conglycinin, an major allergen in soybean. The objective of this study was to explore the alleviating effect and underlying mechanism of green tea polyphenols (GTPs) on β-conglycinin-induced anaphylaxis. Twenty-one-day-old weaned BN rats were sensitized by gavage of β-conglycin and then given drinking water containing 1% GTPs. The results showed that β-conglcyinin sensitized rats had increased serum IgE levels and IL-4 level in spleen cell culture supernatant compared with the control group. However, total IgE, β-conglycin-specific IgE and IL-4 levels were significantly decreased by GTPs, suggesting that it weakened Th2-type immune response and restored cytokine homeostasis. The impact of GTPs on gut microbiota mainly focused on the changes in specific microbes, characterized by a significant increase of Bacteroides and other beneficial bacteria, which would contribute to the recovery of gastrointestinal allergies. This study is the first to demonstrate that GTPs, as good immunomodulator, played an important role in alleviating soybean protein allergy, which were associated with the alterations in gut microbiota. These results contribute to the development and application of green tea and provided an effective nutritional therapy strategy for the prevention and treatment of allergic diseases caused by soybean allergens.
Assessment of immune responses and intestinal flora in BALB/c mice model of wheat food allergy via different sensitization methods
2023, Food Science and Human Wellness
Increasing incidences showed that food allergies have attracted more and more attention from researchers. BALB/c mice were sensitized with wheat gluten combined with aluminum hydroxide adjuvant via intraperitoneal injection, transdermal sensitization, and oral gavage sensitization route. Results showed that all the three sensitization methods could induce allergic symptoms; increase the serum antibody (total immunoglobulin E (IgE), specific IgE, IgG, IgA) and histamine content; promote the secretion of Th2 cytokines (interleukin (IL)-4, IL-5, IL-13) and inflammatory factors (IL-6, IL-17A, IL-10); and inhibit the production of Th1 cytokines (IFN-γ, IL-2). However, the allergic symptoms of mice sensitized by intraperitoneal injection were the most obvious among the three models. The level of serum antibodies in intraperitoneal injection group was significantly higher than control. Subsequently, 16S rRNA sequencing technology was used to analyze the intestinal flora of mice. The results showed that the abundance of Firmicutes in the wheat protein sensitized group was lower than that in the normal group, while the abundance of Bacteroidetes was higher, and Lactobacillus was the difference marker in normal group. Bacterial species diversity analysis showed that the species richness and diversity of intestinal flora in mice were decreased, the difference between mice induced by intraperitoneal injection and normal control group mice was the most significant. Taken together, these results show that among three sensitization methods used to build a mouse model with aluminum hydroxide as adjuvant, intraperitoneal injection is the comparably best way to build a mouse sensitization mode.
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: Supported in part by the National Institutes of Health (NIH) Intramural Program of the NIH Clinical Center.

: Disclosure of potential conflict of interest: Y. J. Huang has received travel support and payment for lectures from the American Academy of Allergy, Asthma & Immunology and has received travel support from the National Academy of Science, Engineering, and Medicine; the National Institutes of Health (NIH), the American College of Chest Physicians, the European Respiratory Society, and the Massachusetts Institute of Technology. S. Bunyavanich has received a grant from the NIH/National Institute of Allergy and Infectious Diseases. L. O'Mahony has consultant arrangements with Alimentary Health Ltd and has received grants from GlaxoSmithKline. D. Y. M. Leung has received a grant from MedImmune; has received consulting fees or honoraria from Novartis, Regeneron, and Sanofi-Aventis; and has received payment for writing or reviewing this manuscript from Omnia-Prova Education Collaborative. A. Muraro has consultant arrangements with Meda, Novartis, and Menarini; is employed by Padua University Hospital; and has received payment for lectures from Meda and Menarini. T. A. Fleisher is President of the American Academy of Allergy, Asthma & Immunology; has received payment for lectures from the Boston City Wide Allergy Meeting, the Louisiana Society of Allergy, Asthma, and Immunology, and the Alaska Society of Allergy, Asthma, and Immunology; and has received royalties as coeditor of Clinical Immunology: Principles and Practice. B. J. Marsland declares that he has no relevant conflicts of interest.

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Reviews and feature articleThe microbiome in allergic disease: Current understanding and future opportunities—2017 PRACTALL document of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology

Section snippets

Microbial ecology

Assessment of the microbiota

Asthma

AD

Food allergy

Strategies to manipulate the microbiome

Analytics

Conclusion

J Allergy Clin Immunol

Immunol Allergy Clin North Am

J Allergy Clin Immunol

J Allergy Clin Immunol

Chest

J Allergy Clin Immunol

J Allergy Clin Immunol

Cell Host Microbe

J Allergy Clin Immunol

Cell Host Microbe

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Antiviral Res

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Curr Biol

J Allergy Clin Immunol

EBioMedicine

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Cell Host Microbe

Gut microbiota: metabolites and host immunity

Nat Rev Immunol

Respiratory symptoms as predictors of 27 year mortality in a representative sample of British adults

BMJ

The relationship between antibiotic therapy in early childhood and the symptoms of allergy in children aged 6-8 years—the questionnaire study results

Int J Occup Med Environ Health

Breastfeeding protects against current asthma up to 6 years of age

J Pediatr

Asthma and 8 years of age in children born by ceasarian section

Thorax

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

J Allergy Clin Immunol

Early infancy microbial and metabolic alterations affect risk of childhood asthma

Sci Transl Med

Innate immunity and asthma risk in Amish and Hutterite farm children

N Engl J Med

Extreme genome reduction in symbiotic bacteria

Nat Rev Microbiol

Genetic determinants of the gut microbiome in UK twins

Cell Host Microbe

Intestinal microbiota in metabolic diseases: from bacterial community structure and functions to species of pathophysiological relevance

Gut Microbes

The microbiome in asthma

Curr Opin Pediatr

Biogeography and individuality shape function in the human skin metagenome

Nature

Genomic approaches to studying the human microbiota

Nature

The human mycobiome in health and disease

Genome Med

Early life dynamics of the human gut virome and bacterial microbiome in infants

Nat Med

The human skin double-stranded DNA virome: topographical and temporal diversity, genetic enrichment, and dynamic associations with the host microbiome

MBio

Analysis of the nasal vestibule mycobiome in patients with allergic rhinitis

Mycoses

Differences in fungi present in induced sputum samples from asthma patients and non-atopic controls: a community based case control study

BMC Infect Dis

Cohort study of airway mycobiome in adult cystic fibrosis patients: differences in community structure between fungi and bacteria reveal predominance of transient fungal elements

J Clin Microbiol

Cluster analysis and clinical asthma phenotypes

Am J Respir Crit Care Med

Longitudinally stable, clinically defined clusters of patients with asthma independently identified in the ADEPT and U-BIOPRED asthma studies

Ann Am Thorac Soc

Gene expression in relation to exhaled nitric oxide identifies novel asthma phenotypes with unique biomolecular pathways

Reviews and feature article
The microbiome in allergic disease: Current understanding and future opportunities—2017 PRACTALL document of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology