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      The Role of Lung and Gut Microbiota in the Pathology of Asthma

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          Abstract

          Asthma is a common chronic respiratory disease affecting more than 300 million people worldwide. Clinical features of asthma and its immunological and molecular etiology vary significantly among patients. An understanding of the complexities of asthma has evolved to the point where precision medicine approaches, including microbiome analysis, are being increasingly recognized as an important part of disease management. Lung and gut microbiota play several important roles in the development, regulation, and maintenance of healthy immune responses. Dysbiosis and subsequent dysregulation of microbiota-related immunological processes affect the onset of the disease, its clinical characteristics, and responses to treatment. Bacteria and viruses are the most extensively studied microorganisms relating to asthma pathogenesis, but other microbes, including fungi and even archaea, can potently influence airway inflammation. This review focuses on recently discovered connections between lung and gut microbiota, including bacteria, fungi, viruses, and archaea, and their influence on asthma.

          Abstract

          Dysregulation of microbiota-related immunological processes affects the onset of asthma, its clinical characteristics, and responses to treatment. Finlay et al. review connections between gut and lungs microbiota and its influence on allergic airway inflammation. This review covers not only the most well-known populations of microbes in the context of asthma—bacteria—but also discusses viruses, fungi, and archaea.

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          Most cited references111

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          The maternal microbiota drives early postnatal innate immune development.

          Postnatal colonization of the body with microbes is assumed to be the main stimulus to postnatal immune development. By transiently colonizing pregnant female mice, we show that the maternal microbiota shapes the immune system of the offspring. Gestational colonization increases intestinal group 3 innate lymphoid cells and F4/80(+)CD11c(+) mononuclear cells in the pups. Maternal colonization reprograms intestinal transcriptional profiles of the offspring, including increased expression of genes encoding epithelial antibacterial peptides and metabolism of microbial molecules. Some of these effects are dependent on maternal antibodies that potentially retain microbial molecules and transmit them to the offspring during pregnancy and in milk. Pups born to mothers transiently colonized in pregnancy are better able to avoid inflammatory responses to microbial molecules and penetration of intestinal microbes.
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            Type 2 inflammation in asthma--present in most, absent in many.

            John Fahy (2015)
            Asthma is one of the most common chronic immunological diseases in humans, affecting people from childhood to old age. Progress in treating asthma has been relatively slow and treatment guidelines have mostly recommended empirical approaches on the basis of clinical measures of disease severity rather than on the basis of the underlying mechanisms of pathogenesis. An important molecular mechanism of asthma is type 2 inflammation, which occurs in many but not all patients. In this Opinion article, I explore the role of type 2 inflammation in asthma, including lessons learnt from clinical trials of inhibitors of type 2 inflammation. I consider how dichotomizing asthma according to levels of type 2 inflammation--into 'T helper 2 (TH2)-high' and 'TH2-low' subtypes (endotypes)--has shaped our thinking about the pathobiology of asthma and has generated new interest in understanding the mechanisms of disease that are independent of type 2 inflammation.
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              Is Open Access

              Archaea and Fungi of the Human Gut Microbiome: Correlations with Diet and Bacterial Residents

              Diet influences health as a source of nutrients and toxins, and by shaping the composition of resident microbial populations. Previous studies have begun to map out associations between diet and the bacteria and viruses of the human gut microbiome. Here we investigate associations of diet with fungal and archaeal populations, taking advantage of samples from 98 well-characterized individuals. Diet was quantified using inventories scoring both long-term and recent diet, and archaea and fungi were characterized by deep sequencing of marker genes in DNA purified from stool. For fungi, we found 66 genera, with generally mutually exclusive presence of either the phyla Ascomycota or Basiodiomycota. For archaea, Methanobrevibacter was the most prevalent genus, present in 30% of samples. Several other archaeal genera were detected in lower abundance and frequency. Myriad associations were detected for fungi and archaea with diet, with each other, and with bacterial lineages. Methanobrevibacter and Candida were positively associated with diets high in carbohydrates, but negatively with diets high in amino acids, protein, and fatty acids. A previous study emphasized that bacterial population structure was associated primarily with long-term diet, but high Candida abundance was most strongly associated with the recent consumption of carbohydrates. Methobrevibacter abundance was associated with both long term and recent consumption of carbohydrates. These results confirm earlier targeted studies and provide a host of new associations to consider in modeling the effects of diet on the gut microbiome and human health.
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                Author and article information

                Contributors
                Journal
                Immunity
                Immunity
                Immunity
                Published by Elsevier Inc.
                1074-7613
                1097-4180
                18 February 2020
                18 February 2020
                18 February 2020
                : 52
                : 2
                : 241-255
                Affiliations
                [1 ]Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
                [2 ]Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
                [3 ]Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada
                [4 ]Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos, Switzerland
                [5 ]Christine Kühne - Center for Allergy Research and Education (CK-CARE), Davos, Switzerland
                Author notes
                []Corresponding author bfinlay@ 123456interchange.ubc.ca
                Article
                S1074-7613(20)30034-0
                10.1016/j.immuni.2020.01.007
                7128389
                32075727
                1055ac77-cd15-4a6a-9337-b4ecffea5a10
                © 2020 Published by Elsevier Inc.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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                Immunology
                Immunology

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