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      Dysbiosis of the gut and lung microbiome has a role in asthma

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          Abstract

          Worldwide 300 million children and adults are affected by asthma. The development of asthma is influenced by environmental and other exogenous factors synergizing with genetic predisposition, and shaping the lung microbiome especially during birth and in very early life. The healthy lung microbial composition is characterized by a prevalence of bacteria belonging to the phyla Bacteroidetes, Actinobacteria, and Firmicutes. However, viral respiratory infections are associated with an abundance of Proteobacteria with genera Haemophilus and Moraxella in young children and adult asthmatics. This dysbiosis supports the activation of inflammatory pathways and contributes to bronchoconstriction and bronchial hyperresponsiveness. Exogenous factors can affect the natural lung microbiota composition positively (farming environment) or negatively (allergens, air pollutants). It is evident that also gut microbiota dysbiosis has a high influence on asthma pathogenesis. Antibiotics, antiulcer medications, and other drugs severely impair gut as well as lung microbiota. Resulting dysbiosis and reduced microbial diversity dysregulate the bidirectional crosstalk across the gut-lung axis, resulting in hypersensitivity and hyperreactivity to respiratory and food allergens. Efforts are undertaken to reconstitute the microbiota and immune balance by probiotics and engineered bacteria, but results from human studies do not yet support their efficacy in asthma prevention or treatment. Overall, dysbiosis of gut and lung seem to be critical causes of the increased emergence of asthma.

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          The Microbiome and the Respiratory Tract.

          Although the notion that "the normal lung is free from bacteria" remains common in textbooks, it is virtually always stated without citation or argument. The lungs are constantly exposed to diverse communities of microbes from the oropharynx and other sources, and over the past decade, novel culture-independent techniques of microbial identification have revealed that the lungs, previously considered sterile in health, harbor diverse communities of microbes. In this review, we describe the topography and population dynamics of the respiratory tract, both in health and as altered by acute and chronic lung disease. We provide a survey of current techniques of sampling, sequencing, and analysis of respiratory microbiota and review technical challenges and controversies in the field. We review and synthesize what is known about lung microbiota in various diseases and identify key lessons learned across disease states.
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            Analysis of the Upper Respiratory Tract Microbiotas as the Source of the Lung and Gastric Microbiotas in Healthy Individuals

            ABSTRACT No studies have examined the relationships between bacterial communities along sites of the upper aerodigestive tract of an individual subject. Our objective was to perform an intrasubject and intersite analysis to determine the contributions of two upper mucosal sites (mouth and nose) as source communities for the bacterial microbiome of lower sites (lungs and stomach). Oral wash, bronchoalveolar lavage (BAL) fluid, nasal swab, and gastric aspirate samples were collected from 28 healthy subjects. Extensive analysis of controls and serial intrasubject BAL fluid samples demonstrated that sampling of the lungs by bronchoscopy was not confounded by oral microbiome contamination. By quantitative PCR, the oral cavity and stomach contained the highest bacterial signal levels and the nasal cavity and lungs contained much lower levels. Pyrosequencing of 16S rRNA gene amplicon libraries generated from these samples showed that the oral and gastric compartments had the greatest species richness, which was significantly greater in both than the richness measured in the lungs and nasal cavity. The bacterial communities of the lungs were significantly different from those of the mouth, nose, and stomach, while the greatest similarity was between the oral and gastric communities. However, the bacterial communities of healthy lungs shared significant membership with the mouth, but not the nose, and marked subject-subject variation was noted. In summary, microbial immigration from the oral cavity appears to be the significant source of the lung microbiome during health, but unlike the stomach, the lungs exhibit evidence of selective elimination of Prevotella bacteria derived from the upper airways.
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              Low gut microbiota diversity in early infancy precedes asthma at school age.

              Low total diversity of the gut microbiota during the first year of life is associated with allergic diseases in infancy, but little is known how early microbial diversity is related to allergic disease later in school age. To assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to the prevalence of different allergic diseases in school age, such as asthma, allergic rhinoconjunctivitis (ARC) and eczema. The microbial diversity and composition was analysed with barcoded 16S rDNA 454 pyrosequencing in stool samples at 1 week, 1 month and 12 months of age in 47 infants which were subsequently assessed for allergic disease and skin prick test reactivity at 7 years of age (ClinicalTrials.gov ID NCT01285830). Children developing asthma (n = 8) had a lower diversity of the total microbiota than non-asthmatic children at 1 week (P = 0.04) and 1 month (P = 0.003) of age, whereas allergic rhinoconjunctivitis (n = 13), eczema (n = 12) and positive skin prick reactivity (n = 14) at 7 years of age did not associate with the gut microbiota diversity. Neither was asthma associated with the microbiota composition later in infancy (at 12 months). Children having IgE-associated eczema in infancy and subsequently developing asthma had lower microbial diversity than those that did not. There were no significant differences, however, in relative abundance of bacterial phyla and genera between children with or without allergic disease. Low total diversity of the gut microbiota during the first month of life was associated with asthma but not ARC in children at 7 years of age. Measures affecting microbial colonization of the infant during the first month of life may impact asthma development in childhood. © 2013 John Wiley & Sons Ltd.
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                Author and article information

                Contributors
                erika.jensen-jarolim@meduniwien.ac.at
                Journal
                Semin Immunopathol
                Semin Immunopathol
                Seminars in Immunopathology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                1863-2297
                1863-2300
                18 February 2020
                18 February 2020
                2020
                : 42
                : 1
                : 75-93
                Affiliations
                [1 ]GRID grid.6583.8, ISNI 0000 0000 9686 6466, The Interuniversity Messerli Research Institute, , Medical University Vienna and University of Veterinary Medicine Vienna, ; Vienna, Austria
                [2 ]GRID grid.22937.3d, ISNI 0000 0000 9259 8492, Center for Pathophysiology, Infectiology and Immunology, , Institute of Pathophysiology and Allergy Research, Medical University Vienna, ; Währinger G. 18-20, 1090 Vienna, Austria
                Author notes

                This article is a contribution to the special issue on Asthma: Novel developments from bench to bedside - Guest Editor: Bianca Schaub

                Author information
                http://orcid.org/0000-0002-2288-2468
                Article
                775
                10.1007/s00281-019-00775-y
                7066092
                32072252
                f2b6256d-5294-420a-80fd-5f2a9100b7f6
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 12 July 2019
                : 15 December 2019
                Funding
                Funded by: Austrian Science Fund FWF
                Award ID: SFB F4606-B28
                Award Recipient :
                Categories
                Review
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2020

                Pathology
                asthma,allergy,microbiome,th2 inflammation,antibiotics,probiotics
                Pathology
                asthma, allergy, microbiome, th2 inflammation, antibiotics, probiotics

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