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
2017; Elsevier BV; Volume: 139; Issue: 4 Linguagem: Inglês
10.1016/j.jaci.2017.02.007
ISSN1097-6825
AutoresYvonne J. Huang, Benjamin J. Marsland, Supinda Bunyavanich, Liam O’Mahony, Donald Y.M. Leung, Antonella Muraro, Thomas A. Fleisher,
Tópico(s)IL-33, ST2, and ILC Pathways
ResumoPRACTALL 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. 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. There is increasing evidence that resident microbial communities in the human gastrointestinal tract, airway, and skin contribute to health and disease. This complex relationship between the microbiota (Table I) and the human host could lend itself to manipulation to benefit the host. This fits with recognition that the microbiome plays an important role in early immunologic development, raising the possibility that experimental manipulation can modulate the immune system.1Rooks M.G. Garrett W.S. Gut microbiota: metabolites and host immunity.Nat Rev Immunol. 2016; 16: 341-352Crossref PubMed Google Scholar Linking the microbiota to both immune development and response heightens the potential that the microbiome plays an important role in the development and manifestations of allergic diseases. In fact, at a clinical level, this connection had its origins with observations in the 1980s that children in large families had a lower incidence of allergic rhinitis and atopic dermatitis (AD) compared with children from smaller families, observations that led to the hygiene hypothesis.2Carpenter L. Beral V. Stachan D. Ebi-Kryston K.L. Inskip H. Respiratory symptoms as predictors of 27 year mortality in a representative sample of British adults.BMJ. 1989; 299: 357-361Crossref PubMed Google Scholar Subsequent epidemiologic studies yielded data documenting a lower rate of allergic disease in children raised in European rural environments linked to raw milk and stable exposure, particularly during the first year of life.3van Neerven R.J. Knol E.F. Heck J.M. Savelkoul H.F. Which factors in raw cow’s milk contribute to protection against allergies?.J Allergy Clin Immunol. 2012; 130: 853-858Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 4Von Mutius E. Radon K. Living on a farm: impact on asthma induction and clinical course.Immunol Allergy Clin North Am. 2008; 28: 631-647Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar A host of additional studies established that in addition to the findings noted above, absence of early antibiotic exposure, exclusive breast-feeding for the first 4 months of life, vaginal delivery, furry pets in the home during infancy, lack of maternal antibiotic use during pregnancy, and maternal animal exposure during pregnancy all were associated with lower rates of allergic disease.5Raciborski F. Tomaszewska A. Komorowski J. Samel-Kowalik P. Bialoszewski A.Z. Walkiewicz A. et al.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. 2012; 25: 470-480Crossref PubMed Google Scholar, 6Silvers K.M. Frampton C.M. Wickens K. Pattemore P.K. Ingham T. Fishwick D. et al.Breastfeeding protects against current asthma up to 6 years of age.J Pediatr. 2012; 160: 991-996Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar, 7Roduit C. Scholtens S. de Jongste J.C. Wijga A.H. Gerritsen J. Postma D.S. et al.Asthma and 8 years of age in children born by ceasarian section.Thorax. 2009; 64: 107-113Crossref PubMed Scopus (0) Google Scholar, 8Fujimura K.E. Johnson C.C. Ownby D.R. Cox M.J. Brodie E.L. Havastad S.L. et al.Man’s best friend? The effect of pet ownership on house dust microbial communities.J Allergy Clin Immunol. 2010; 126: 410-412Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar, 9Lynch S.V. Wood R.A. Boushey H. Bacharier L.B. Bloomberg G.R. Kattan M. et al.Effects of early-life exposure to allergens and bacteria on recurrent wheeze and atopy in urban children.J Allergy Clin Immunol. 2014; 134: 593-601.e12Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar Taken together, these clinical observations established a strong link between microbes and the development of allergic disease.Table IKey definitionsMicrobiomeThe sum of microbes, their genomic elements, and interactions in a given ecological nicheMicrobiotaThe sum of microbes found in a given ecological nicheRichnessThe number of species or taxa found in a sample or nicheEvennessThe relative distribution of species or taxa in a sample or nicheDiversityA calculated index that incorporates measures of richness and species distribution. Many different diversity measures exist:•α-diversity: within a sample or site•β-diversity: reflects differences in species composition between samples or sitesTaxon or taxaSynonymous with operational taxonomic unit (OTU); for bacteria identified by using 16S rRNA gene-based analysis, a taxon is defined as a group of species with very similar sequence homology (eg, ≥97%).DysbiosisDescriptive term for imbalance in a microbial ecosystem; for example, dysbiosis of the intestinal or respiratory tract associated with a disease state compared with healthPathobiontAn organism normally part of the microbiota (commensal) but able to promote pathologic disease under certain host conditions; examples include Clostridium difficile, Haemophilus influenzae, and Klebsiella pneumoniae Open table in a new tab The science connecting the microbiome to immunologically mediated disorders, including allergic disease, has been advanced by the capacity to catalog microbiota and define imbalances in microbial communities, which are referred to as dysbiosis (Table I). These studies have used next-generation DNA sequencing to profile the total bacterial community in a particular site, including evaluation of the richness, evenness, and diversity of the species present (Table I). This approach represents an important step forward because standard culture methods typically detect only approximately 1% of the bacterial community in a particular site when compared with molecular methods. However, there remain limitations to these data, including the recognition that many studies characterizing bacterial content have not captured other microbiota, such as fungi and viruses. Nonetheless, the potential contribution of the microbiota to the documented increase in rates of asthma, AD, and food allergy has become increasingly appealing to consider. The clinical findings noted above, together with the increased rate of allergic disease, suggest that urban living in Western society is a major contributor to this change. There are now clinical research studies and animal studies that link the microbiota of the gastrointestinal tract, as well as those of the skin and respiratory tract, to allergic disease. Two recent examples include a study that suggests that microbiota (together with bacterial metabolic products) during early infancy affects the risk of childhood asthma.10Arrieta M.C. Stiemsma L.T. Dimitriu P.A. Thorson L. Russell S. Yurist-Doutsch S. et al.Early infancy microbial and metabolic alterations affect risk of childhood asthma.Sci Transl Med. 2015; 7: 1-14Crossref Scopus (106) Google Scholar In addition, in genetically comparable populations, environmental exposures linked to varied microbial content affect the development of asthma by shaping the innate immune response.11Stein M.M. Hrusch C.L. Gozdz J. Igartua C. Pivniouk V. Murray S.E. et al.Innate immunity and asthma risk in Amish and Hutterite farm children.N Engl J Med. 2016; 375: 411-421Crossref PubMed Scopus (0) Google Scholar These and many other studies clearly provide very strong connections between bacterial microbiota and the development of allergic disease. However, most of these studies have focused on one organ system and have used varied end points. Thus there remains a host of unanswered questions to further clarify and expand on these connections. Finally, it has been suggested that modifying the microbiome to the host's advantage could prove to be an approach for preventing and/or treating allergic disease. 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 within specific host niches.12McCutcheon J.P. Moran N.A. Extreme genome reduction in symbiotic bacteria.Nat Rev Microbiol. 2011; 10: 13-26Crossref PubMed Scopus (0) Google Scholar DNA-sequencing techniques have facilitated more in-depth analysis of the gastrointestinal tract, skin, genitourinary tract, and lung microbiota, revealing a microbial superorgan residing in symbiosis with host mucosal surfaces. These communities evolve within a host from birth, constantly being fine-tuned to maintain a homeostatic balance with the host's immune system. This evolution is influenced by host factors, such as adaptive and innate immune responses13Goodrich G.K. Davenport E.R. Beaumont M. Jackson M.A. Knight R. Ober C. et al.Genetic determinants of the gut microbiome in UK twins.Cell Host Microbe. 2016; 11: 731-743Abstract Full Text Full Text PDF Scopus (24) Google Scholar; external factors, such as diet, medication, and toxin exposure; infection; and illness. Given the potentially vast number of interactions existing between microbes, diet/nutrients, host metabolism, immune responses, and xenobiotics, it has been extremely difficult to model population dynamics experimentally. The composition and diversity of the microbiome varies across body sites, resulting in a series of unique habitats within and between subjects that can change dramatically over time. The gastrointestinal tract has the greatest number and diversity of microbes and is dominated by facultative and strictly anaerobic bacteria of the phyla Firmicutes, Bacteroidetes, Actinobacteria, Verrucomicrobia, and Proteobacteria.14Clavel T. Desmarchelier C. Haller D. Gérard P. Rohn S. Lepage P. et al.Intestinal microbiota in metabolic diseases: from bacterial community structure and functions to species of pathophysiological relevance.Gut Microbes. 2014; 5: 544-551Crossref PubMed Scopus (16) Google Scholar The dominant microbial phyla of the healthy human lung also include Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria, in addition to Fusobacteria.15Noval Rivas M. Crother T.R. Arditi M. The microbiome in asthma.Curr Opin Pediatr. 2016; 6: 764-771Crossref Scopus (0) Google Scholar Bacterial communities differ across the skin surface, and this biogeography is dependent on pH, temperature, moisture, sebum content, and topography.16Oh J. Byrd A.L. Deming C. Conlan S. Kong H.H. Segre J.A. NISC Comparative Sequencing ProgramBiogeography and individuality shape function in the human skin metagenome.Nature. 2014; 514: 59-64Crossref PubMed Scopus (106) Google Scholar Importantly, changes in the composition, metabolic activity, or both of the gut, lung, and skin microbiomes have been associated with asthma, AD, and food allergy, respectively. 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.17Weinstock G.M. Genomic approaches to studying the human microbiota.Nature. 2012; 489: 250-256Crossref PubMed Scopus (0) Google Scholar However, comparative analysis between different studies has been problematic because of differences in phenotyping, sample collection and storage, DNA isolation, amplification, and sequencing protocols. In addition, these analyses depend on the quality of available databases that allow the 16S rRNA gene sequences to be annotated with a particular bacterial taxon and the types of analysis and data interpretation tools that are used. Consensus on best practice experimental conditions and data analysis tools is urgently required to prevent potentially misleading interpretations of the data. In addition to the assessment of changes in bacterial community composition and diversity, it is important to better understand the functional consequences of these changes. Meaningful in vitro and in vivo models are required to link changes in microbiome signatures with disease-relevant end points. This requires that target bacterial strains are isolated, cultured, and well characterized. In addition, new and improved tools to evaluate the fungal and viral components within each niche habitat will also need to be developed to fully understand the role of the human microbiome in health and disease. Despite the technical and analytic challenges involved in studying fungal and viral communities (as discussed later), several studies have described the types of fungal and viral species detected in different body sites, including the gut, respiratory tract, and skin.18Cui L. Morris A. Ghedin E. The human mycobiome in health and disease.Genome Med. 2013; 5: 63Crossref PubMed Scopus (51) Google Scholar, 19Lim E.S. Zhou Y. Zhao G. Bauer I.K. Droit L. 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Differences in fungi present in induced sputum samples from asthma patients and non-atopic controls: a community based case control study.BMC Infect Dis. 2013; 13: 69Crossref PubMed Scopus (27) Google Scholar However, the clinical implications of such findings remain unclear given poor insight into the functional consequences of these microbial associations in disease or health, a focus on DNA viruses (eg, bacteriophages), and limited understanding of the dynamics of human-associated fungal and viral communities. For example, a study of sputum microbiota in patients with cystic fibrosis found greater fluctuation in fungal community than bacterial community composition, which suggests that inhaled fungal elements might be more transient in the respiratory microbiomes of some subjects.23Kramer R. Sauer-Heilborn A. Welte T. Guzman C.A. Abraham W.R. Höfle M.G. 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. 2015; 53: 2900-2907Crossref PubMed Google Scholar 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.24Haldar P. Pavord I.D. Shaw D.E. Berry M.A. Thomas M. Brightling C.E. et al.Cluster analysis and clinical asthma phenotypes.Am J Respir Crit Care Med. 2008; 178: 218-224Crossref PubMed Scopus (788) Google Scholar, 25Loza M.J. Adcock I. Auffray C. Chung K.F. Djukanovic R. Sterk P.J. et al.Longitudinally stable, clinically defined clusters of patients with asthma independently identified in the ADEPT and U-BIOPRED asthma studies.Ann Am Thorac Soc. 2016; 13: S102-S103PubMed Google Scholar, 26Modena B.D. Tedrow J.R. Milosevic J. Bleecker E.R. Meyers D.A. Wu W. et al.Gene expression in relation to exhaled nitric oxide identifies novel asthma phenotypes with unique biomolecular pathways.Am J Respir Crit Care Med. 2014; 190: 1363-1372Crossref PubMed Scopus (28) Google Scholar, 27Moore W.C. Fitzpatrick A.M. Li X. Hastie A.T. Li H. Meyers D.A. et al.Clinical heterogeneity in the severe asthma research program.Ann Am Thorac Soc. 2013; 10: S118-S124Crossref PubMed Scopus (21) Google Scholar, 28Fahy J.V. Type 2 inflammation in asthma—present in most, absent in many.Nat Rev Immunol. 2015; 15: 57-65Crossref PubMed Scopus (101) Google Scholar Microbes have long been postulated to play a role in asthma and might also shape its heterogeneity.29Smits H.H. Hiemstra P.S. Prazeres da Costa C. Ege M. Edwards M. Garn H. et al.Microbes and asthma: opportunities for intervention.J Allergy Clin Immunol. 2016; 137: 690-697Abstract Full Text Full Text PDF PubMed Google Scholar, 30Sutherland E.R. Martin R.J. Asthma and atypical bacterial infection.Chest. 2007; 132: 1962-1966Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar These roles include the following contexts: (1) the effect of early-life exposure to microbially rich environments on susceptibility to childhood asthma; (2) the role of the microbiota in immune system development; (3) the effects of acute viral infections and patterns of respiratory tract bacterial colonization on childhood asthma; and (4) the potential role of bronchial colonization by particular bacteria in phenotypes of asthma. Increasingly, further evidence in support of these roles has been derived from studies that considered the ecology of microbial communities found in different sample types or organ-specific niches (microbiota). New insights from these and other human microbiome investigations are blurring classical concepts of “colonization” and “infection,”31Casadevall A. Pirofski L.A. Microbiology: ditch the term pathogen.Nature. 2014; 516: 165-166Crossref PubMed Scopus (26) Google Scholar, 32Byrd A.L. Segre J.A. Infectious disease. Adapting Koch's postulates.Science. 2016; 351: 224-226Crossref PubMed Scopus (17) Google Scholar leading researchers to consider new hypotheses about the role of microbiota-host interactions in patients with disease, including the inception, chronicity, and severity of asthma. Recent applications of modern molecular and bioinformatic tools to understand the composition and functional potential of microbial communities has significantly expanded our knowledge of patterns in the microbiome linked to asthma.10Arrieta M.C. Stiemsma L.T. Dimitriu P.A. Thorson L. Russell S. Yurist-Doutsch S. et al.Early infancy microbial and metabolic alterations affect risk of childhood asthma.Sci Transl Med. 2015; 7: 1-14Crossref Scopus (106) Google Scholar, 33Denner D.R. Sangwan N. Becker J.B. Hogarth D.K. Oldham J. Castillo J. et al.Corticosteroid therapy and airflow obstruction influence the bronchial microbiome, which is distinct from that of bronchoalveolar lavage in asthmatic airways.J Allergy Clin Immunol. 2016; 137: 1398-1405.e3Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar, 34Huang Y.J. Nariya S. Harris J.M. Lynch S.V. Choy D.F. Arron J.R. et al.The airway microbiome in patients with severe asthma: Associations with disease features and severity.J Allergy Clin Immunol. 2015; 136: 874-884Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar, 35Huang Y.J. Nelson C.E. Brodie E.L. Desantis T.Z. Baek M.S. Liu J. et al.Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma.J Allergy Clin Immunol. 2011; 127 (e1-3): 372-381Abstract Full Text Full Text PDF PubMed Scopus (246) Google Scholar, 36Marri P.R. Stern D.A. Wright A.L. Billheimer D. Martinez F.D. Asthma-associated differences in microbial composition of induced sputum.J Allergy Clin Immunol. 2013; 131 (e1-3): 346-352Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar, 37Simpson J.L. Daly J. Baines K.J. Yang I.A. Upham J.W. Reynolds P.N. et al.Airway dysbiosis: Haemophilus influenzae and Tropheryma in poorly controlled asthma.Eur Respir J. 2016; 47: 792-800Crossref PubMed Scopus (0) Google Scholar, 38Teo S.M. Mok D. Pham K. Kusel M. Serralha M. Troy N. et al.The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development.Cell Host Microbe. 2015; 17: 704-715Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar, 39Goleva E. Jackson L.P. Harris J.K. Robertson C.E. Sutherland E.R. Hall C.F. et al.The effects of airway microbiome on corticosteroid responsiveness in asthma.Am J Respir Crit Care Med. 2013; 188: 1193-1201Crossref PubMed Scopus (70) Google Scholar, 40Durack J. Lynch S.V. Nariya S. Bhakta N.R. Beigelman A. Castro M. et al.Features of the bronchial bacterial microbiome associated with atopy, asthma and responsiveness to inhaled corticosteroid treatment.J Allergy Clin Immunol. 2016; ([Epub ahead of print])PubMed Google Scholar, 41Barcik W. Pugin B. Westernann P. Perez N.R. Ferst R. Wawrzyniak M. et al.Histamine-secreting microbes are increased in the gut of adult asthma patients.J Allergy Clin Immunol. 2016; 138: 1491-1494Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 42Hilty M. Burke C. Pedro H. Cardenas P. Bush A. Bossley C. et al.Disordered microbial communities in asthmatic airways.PLoS One. 2010; 5 (e8578)Crossref PubMed Scopus (483) Google Scholar, 43Green B.J. Wiriyachaiporn S. Grainge C. Rogers G.B. Kehagia V. Lau L. et al.Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma.PLoS One. 2014; 9 (e100645)Crossref Scopus (183) Google Scholar To date, the predominant focus has been on bacteria, and a number of studies have described asthma-associated differences in the composition of bacterial microbiota found in the respiratory (upper and lower) and gastrointestinal tracts.10Arrieta M.C. Stiemsma L.T. Dimitriu P.A. Thorson L. Russell S. Yurist-Doutsch S. et al.Early infancy microbial and metabolic alterations affect risk of childhood asthma.Sci Transl Med. 2015; 7: 1-14Crossref Scopus (106) Google Scholar, 34Huang Y.J. Nariya S. Harris J.M. Lynch S.V. Choy D.F. Arron J.R. et al.The airway microbiome in patients with severe asthma: Associations with disease features and severity.J Allergy Clin Immunol. 2015; 136: 874-884Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar, 35Huang Y.J. Nelson C.E. Brodie E.L. Desantis T.Z. Baek M.S. Liu J. et al.Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma.J Allergy Clin Immunol. 2011; 127 (e1-3): 372-381Abstract Full Text Full Text PDF PubMed Scopus (246) Google Scholar, 36Marri P.R. Stern D.A. Wright A.L. Billheimer D. Martinez F.D. Asthma-associated differences in microbial composition of induced sputum.J Allergy Clin Immunol. 2013; 131 (e1-3): 346-352Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar, 37Simpson J.L. Daly J. Baines K.J. Yang I.A. Upham J.W. Reynolds P.N. et al.Airway dysbiosis: Haemophilus influenzae and Tropheryma in poorly controlled asthma.Eur Respir J. 2016; 47: 792-800Crossref PubMed Scopus (0) Google Scholar, 38Teo S.M. Mok D. Pham K. Kusel M. Serralha M. Troy N. et al.The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development.Cell Host Microbe. 2015; 17: 704-715Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar, 39Goleva E. Jackson L.P. Harris J.K. Robertson C.E. Sutherland E.R. Hall C.F. et al.The effects of airway microbiome on corticosteroid responsiveness in asthma.Am J Respir Crit Care Med. 2013; 188: 1193-1201Crossref PubMed Scopus (70) Google Scholar, 40Durack J. Lynch S.V. Nariya S. Bhakta N.R. Beigelman A. Castro M. et al.Features of the bronchial bacterial microbiome associated with atopy, asthma and responsiveness to inhaled corticosteroid treatment.J Allergy Clin Immunol. 2016; ([Epub ahead of print])PubMed Google Scholar, 41Barcik W. Pugin B. Westernann P. Perez N.R. Ferst R. Wawrzyniak M. et al.Histamine-secreting microbes are increased in the gut of adult asthma patients.J Allergy Clin Immunol. 2016; 138: 1491-1494Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 44Fujimura K.E. Sitarik A.R. Havstad S. Lin D.L. Levan S. Fadrosh D. et al.Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation.Nat Med. 2016; 22: 1187-1191Crossref PubMed Scopus (0) Google Scholar For example, in the lower respiratory tract a repeating signature is asthma-associated enrichment in members of Proteobacteria, a large phylum representing many species with known potential to cause respiratory illnesses.33Denner D.R. Sangwan N. Becker J.B. Hogarth D.K. Oldham J. Castillo J. et al.Corticosteroid therapy and airflow obstruction influence the bronchial microbiome, which is distinct from that of bronchoalveolar lavage in asthmatic airways.J Allergy Clin Immunol. 2016; 137: 1398-1405.e3Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar, 34Huang Y.J. Nariya S. Harris J.M. Lynch S.V. Choy D.F. Arron J.R. et al.The airway microbiome in patients with severe asthma: Associations with disease features and severity.J Allergy Clin Immunol. 2015; 136: 874-884Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar, 35Huang Y.J. Nelson C.E. Brodie E.L. Desantis T.Z. Baek M.S. Liu J. et al.Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma.J Allergy Clin Immunol. 2011; 127 (e1-3): 372-381Abstract Full Text Full Text PDF PubMed Scopus (246) Google Scholar, 36Marri P.R. Stern D.A. Wright A.L. Billheimer D. Martinez F.D. Asthma-associated differences in microbial composition of induced sputum.J Allergy Clin Immunol. 2013; 131 (e1-3): 346-352Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar, 37Simpson J.L. Daly J. Baines K.J. Yang I.A. Upham J.W. Reynolds P.N. et al.Airway dysbiosis: Haemophilus influenzae and Tropheryma in poorly controlled asthma.Eur Respir J. 2016; 47: 792-800Crossref PubMed Scopus (0) Google Scholar, 39Goleva E. Jackson L.P. Harris J.K. Robertson C.E. Sutherland E.R. Hall C.F. et al.The effects of airway microbiome on corticosteroid responsiveness in asthma.Am J Respir Crit Care Med. 2013; 188: 1193-1201Crossref PubMed Scopus (70) Google Scholar, 40Durack J. Lynch S.V. Nariya S. Bhakta N.R. Beigelman A. Castro M. et al.Features of the bronchial bacterial microbiome associated with atopy, asthma and responsiveness to inhaled corticosteroid treatment.J Allergy Clin Immunol. 2016; ([Epub ahead of print])PubMed Google Scholar, 42Hilty M. Burke C. Pedro H. Cardenas P. Bush A. Bossley C. et al.Disordered microbial communities in asthmatic airways.PLoS One. 2010; 5 (e8578)Crossref PubMed Scopus (483) Google Scholar, 43Green B.J. Wiriyachaiporn S. Grainge C. Rogers G.B. Kehagia V. Lau L. et al.Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma.PLoS One. 2014; 9 (e100645)Crossref Scopus (183) Google Scholar These include members of the genera Haemophilus, Moraxella, Neisseria, and Streptococcus (Box 1).Box 1Bacterial genera implicated in asthma or asthma-related features (from recent microbiota studies)Tabled 1Bacterial genusMicrobiome compartmentAsthma contextHaemophilusRespiratoryIncrease associated with asthma in children and adultsNeisseriaRespiratoryIncrease associated with asthma in adultsMoraxellaRespiratoryIncrease associated with asthma in children and adultsStreptococcusRespiratoryIncrease associated with asthma in childrenLactobacillusGastrointestinal, respiratoryDecrease associated with asthma in children and adultsBifidobacteriumGastrointestinalDecrease associated with risk for asthma development in childhoodFaecalibacteriumGastrointestinalDecrease associated with risk for asthma development in childhoodAkkermansiaGastrointestinalDecrease associated with risk for asthma development in childhoodMorganella morganiiGastrointestinalIncrease associated with asthma in nonobese adults Open table in a new
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