Microbiome, Metabolism, and Immunoregulation of Asthma: An American Thoracic Society and National Institute of Allergy and Infectious Diseases Workshop Report

This report presents the proceedings from a workshop titled “Microbiome, Metabolism and Immunoregulation of Asthma” that was held virtually May 13 and 14, 2021. The workshop was jointly sponsored by the American Thoracic Society (Assembly on Allergy, Immunology, and Inflammation) and the National Institute of Allergy and Infectious Diseases. It convened an interdisciplinary group of experts with backgrounds in asthma immunology, microbiome science, metabolomics, computational biology, and translational pulmonary research. The main purpose was to identify key scientific gaps and needs to further advance research on microbial and metabolic mechanisms that may contribute to variable immune responses and disease heterogeneity in asthma. Discussions were structured around several topics, including 1) immune and microbial mechanisms of asthma pathogenesis in murine models, 2) the role of microbes in pediatric asthma exacerbations, 3) dysregulated metabolic pathways in asthma associated with obesity, 4) metabolism effects on macrophage function in adipose tissue and the lungs, 5) computational approaches to dissect microbiome–metabolite links, and 6) potential confounders of microbiome–disease associations in human studies. This report summarizes the major points of discussion, which included identification of specific knowledge gaps, challenges, and suggested directions for future research. These include questions surrounding mechanisms by which microbiota and metabolites shape host health versus an allergic or asthmatic state; direct and indirect influences of other biological factors, exposures, and comorbidities on these interactions; and ongoing technical and analytical gaps for clinical translation.

[1]  Yanling Zhang,et al.  Itaconate and itaconate derivatives target JAK1 to suppress alternative activation of macrophages. , 2022, Cell metabolism.

[2]  S. Lynch,et al.  Maternal gut microbiome regulates immunity to RSV infection in offspring , 2021, The Journal of experimental medicine.

[3]  I. Adcock,et al.  Relationship between type 2 cytokine and inflammasome responses in obesity-associated asthma. , 2021, The Journal of allergy and clinical immunology.

[4]  F. Gilliland,et al.  US Childhood Asthma Incidence Rate Patterns From the ECHO Consortium to Identify High-Risk Groups for Primary Prevention. , 2021, JAMA pediatrics.

[5]  K. Baines,et al.  Role of the NLRP3 inflammasome in asthma: Relationship with neutrophilic inflammation, obesity, and therapeutic options. , 2021, The Journal of allergy and clinical immunology.

[6]  E. Crestani,et al.  Notch4 signaling limits regulatory T-cell-mediated tissue repair and promotes severe lung inflammation in viral infections , 2021, Immunity.

[7]  J. Round,et al.  Microbiota-antibody interactions that regulate gut homeostasis. , 2021, Cell host & microbe.

[8]  K. Bønnelykke,et al.  Characteristics and Mechanisms of a Sphingolipid-associated Childhood Asthma Endotype. , 2021, American journal of respiratory and critical care medicine.

[9]  F. Trottein,et al.  The lung–gut axis during viral respiratory infections: the impact of gut dysbiosis on secondary disease outcomes , 2021, Mucosal Immunology.

[10]  D. Ledford,et al.  Mechanisms of non-type 2 asthma. , 2020, Current opinion in immunology.

[11]  R. Knight,et al.  Host variables confound gut microbiota studies of human disease , 2020, Nature.

[12]  H. Renz,et al.  Obesity and asthma. , 2020, The Journal of allergy and clinical immunology.

[13]  O. Pedersen,et al.  Gut microbiota in human metabolic health and disease , 2020, Nature Reviews Microbiology.

[14]  R. Geha,et al.  A regulatory T cell Notch4-GDF15 axis licenses tissue inflammation in asthma , 2020, Nature Immunology.

[15]  L. Chang,et al.  Integration of metagenomics‐metabolomics reveals specific signatures and functions of airway microbiota in mite‐sensitized childhood asthma , 2020, Allergy.

[16]  H. Grasemann,et al.  Oxidative stress and obesity-related asthma. , 2020, Paediatric respiratory reviews.

[17]  J. Rathmell,et al.  Immunometabolism: From basic mechanisms to translation , 2020, Immunological reviews.

[18]  M. Sokolowska,et al.  The Role of Lung and Gut Microbiota in the Pathology of Asthma , 2020, Immunity.

[19]  National Institute of Allergy and Infectious Disease , 2020, Definitions.

[20]  R. Hamanaka,et al.  Tissue Resident Alveolar Macrophages Do Not Rely on Glycolysis for LPS-induced Inflammation. , 2020, American journal of respiratory cell and molecular biology.

[21]  G. Weinstock,et al.  The upper-airway microbiota and loss of asthma control among asthmatic children , 2019, Nature Communications.

[22]  I. Adcock,et al.  Role of Metabolic Reprogramming in Pulmonary Innate Immunity and Its Impact on Lung Diseases , 2019, Journal of Innate Immunity.

[23]  M. Shaffer,et al.  AMON: annotation of metabolite origins via networks to integrate microbiome and metabolome data , 2019, BMC Bioinformatics.

[24]  H. Boushey,et al.  Distinct Nasal Airway Bacterial Microbiota Differentially Relate to Exacerbation in Pediatric Asthma. , 2019, The Journal of allergy and clinical immunology.

[25]  I. Adcock,et al.  Functional effects of the microbiota in chronic respiratory disease. , 2019, The Lancet. Respiratory medicine.

[26]  L. Que,et al.  Bioenergetic Differences in the Airway Epithelium of Lean Versus Obese Asthmatics Are Driven by Nitric Oxide and Reflected in Circulating Platelets. , 2019, Antioxidants & redox signaling.

[27]  A. Kraneveld,et al.  The crosstalk between microbiome and asthma: Exploring associations and challenges , 2019, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[28]  H. Hammad,et al.  The Cytokines of Asthma. , 2019, Immunity.

[29]  A. Dixon,et al.  Diet and Metabolism in the Evolution of Asthma and Obesity. , 2019, Clinics in chest medicine.

[30]  L. Wood,et al.  Saturated fatty acids, obesity, and the nucleotide oligomerization domain–like receptor protein 3 (NLRP3) inflammasome in asthmatic patients , 2019, The Journal of allergy and clinical immunology.

[31]  L. Russo,et al.  Properties and functions of adipose tissue macrophages in obesity , 2018, Immunology.

[32]  Stephen C. Watts,et al.  Airway Microbiota Dynamics Uncover a Critical Window for Interplay of Pathogenic Bacteria and Allergy in Childhood Respiratory Disease , 2018, Cell Host & Microbe.

[33]  R. Gangnon,et al.  Association of rhinovirus species with common cold and asthma symptoms and bacterial pathogens. , 2017, The Journal of allergy and clinical immunology.

[34]  E. Forno,et al.  Obesity and asthma , 2018, The Journal of allergy and clinical immunology.

[35]  A. Agrawal,et al.  Mitochondrial Dysfunction Linking Obesity and Asthma , 2017, Annals of the American Thoracic Society.

[36]  Ulrich Steinhoff,et al.  IL-17 and TNF-α Are Key Mediators of Moraxella catarrhalis Triggered Exacerbation of Allergic Airway Inflammation , 2017, Front. Immunol..

[37]  Nichole Reisdorph,et al.  Microbiome and metabolome data integration provides insight into health and disease. , 2017, Translational research : the journal of laboratory and clinical medicine.

[38]  S. Janga,et al.  Community-acquired rhinovirus infection is associated with changes in the airway microbiome. , 2017, The Journal of allergy and clinical immunology.

[39]  Mario Castro,et al.  Features of the bronchial bacterial microbiome associated with atopy, asthma, and responsiveness to inhaled corticosteroid treatment , 2017, Journal of Allergy and Clinical Immunology.

[40]  W. Liao,et al.  Influence of diet on the gut microbiome and implications for human health , 2017, Journal of Translational Medicine.

[41]  H. Boushey,et al.  Lactobacillus johnsonii Supplementation Attenuates Respiratory Viral Infection via Metabolic Reprogramming and Immune Cell Modulation , 2017, Mucosal Immunology.

[42]  A. Dahlin,et al.  Asthma Metabolomics and the Potential for Integrative Omics in Research and the Clinic , 2017, Chest.

[43]  A. Levin,et al.  Neonatal gut microbiota associates with childhood multi–sensitized atopy and T–cell differentiation , 2016, Nature Medicine.

[44]  S. Erzurum,et al.  Increased mitochondrial arginine metabolism supports bioenergetics in asthma. , 2016, The Journal of clinical investigation.

[45]  K. Riesbeck,et al.  Moraxella catarrhalis induces CEACAM3‐Syk‐CARD9‐dependent activation of human granulocytes , 2016, Cellular microbiology.

[46]  J. Nicholson,et al.  Impact of the gut microbiota on inflammation, obesity, and metabolic disease , 2016, Genome Medicine.

[47]  Casey M. Theriot,et al.  Metabolic Model-Based Integration of Microbiome Taxonomic and Metabolomic Profiles Elucidates Mechanistic Links between Ecological and Metabolic Variation , 2016, mSystems.

[48]  N. Suttorp,et al.  Streptococcus pneumoniae-Induced Oxidative Stress in Lung Epithelial Cells Depends on Pneumococcal Autolysis and Is Reversible by Resveratrol. , 2015, The Journal of infectious diseases.

[49]  Ronald E Gangnon,et al.  Detection of pathogenic bacteria during rhinovirus infection is associated with increased respiratory symptoms and asthma exacerbations. , 2014, The Journal of allergy and clinical immunology.

[50]  T. Junt,et al.  Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis , 2014, Nature Medicine.

[51]  M. Fischbach,et al.  A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice , 2013, The ISME Journal.

[52]  S. Wenzel,et al.  Nitric oxide and related enzymes in asthma: relation to severity, enzyme function and inflammation , 2012, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[53]  K. Bønnelykke,et al.  Association of bacteria and viruses with wheezy episodes in young children: prospective birth cohort study , 2010, BMJ : British Medical Journal.

[54]  N. Probst-Hensch,et al.  Pulmonary Physiology and Pathophysiology in Obesity Obesity and lung inflammation , 2010 .

[55]  Jian-Dong Li,et al.  Mucin gene (MUC 2 and MUC 5AC) upregulation by Gram-positive and Gram-negative bacteria. , 1998, Biochimica et biophysica acta.