The role of airways microbiota on local and systemic diseases: a rationale for probiotics delivery to the respiratory tract.

INTRODUCTION Recent discoveries in the field of lung microbiota have enabled the investigation of new therapeutic interventions involving the use of inhaled probiotics. AREAS COVERED This review provides an overview of what is known about the correlation between airway dysbiosis and the development of local and systemic diseases, and how this knowledge can be exploited for therapeutic interventions. In particular, the review focused on attempts to formulate probiotics that can be deposited directly on the airways. EXPERT OPINION Despite considerable progress since the emergence of respiratory microbiota restoration as a new research field, numerous clinical implications and benefits remain to be determined. In the case of local diseases, once the pathophysiology is understood, manipulating the lung microbiota through probiotic administration is an approach that can be exploited. In contrast, the effect of pulmonary dysbiosis on systemic diseases remains to be clarified; however, this approach could represent a turning point in their treatment.

[1]  Xikun Zhou,et al.  Lung microbiome: new insights into the pathogenesis of respiratory diseases , 2024, Signal transduction and targeted therapy.

[2]  David M. Holtzman,et al.  Current understanding of the Alzheimer’s disease-associated microbiome and therapeutic strategies , 2024, Experimental & molecular medicine.

[3]  P. Capaccio,et al.  Topical administration of S. salivarius 24SMB-S. oralis 89a in children with adenoidal disease: a double-blind controlled trial , 2023, European journal of pediatrics.

[4]  V. Fainardi,et al.  Development of inhalation powders containing lactic acid bacteria with antimicrobial activity against Pseudomonas aeruginosa. , 2023, International journal of antimicrobial agents.

[5]  A. Castaldo,et al.  Lung Microbiome as a Treatable Trait in Chronic Respiratory Disorders , 2023, Lung.

[6]  Thuy T B Phung,et al.  Efficient symptomatic treatment and viral load reduction for children with influenza virus infection by nasal-spraying Bacillus spore probiotics , 2023, Scientific reports.

[7]  O. Sheils,et al.  The Lung Microbiome in COPD and Lung Cancer: Exploring the Potential of Metal-Based Drugs , 2023, International journal of molecular sciences.

[8]  G. Maisetta,et al.  Lactobacillus Probiotic Strains Differ in Their Ability to Adhere to Human Lung Epithelial Cells and to Prevent Adhesion of Clinical Isolates of Pseudomonas aeruginosa from Cystic Fibrosis Lung , 2023, Microorganisms.

[9]  N. Yuksel,et al.  Lung Microbiota: Its Relationship to Respiratory System Diseases and Approaches for Lung-Targeted Probiotic Bacteria Delivery , 2023, Molecular pharmaceutics.

[10]  C. Greene,et al.  Basic, translational and clinical aspects of bronchiectasis in adults , 2023, European Respiratory Review.

[11]  Fang Wang,et al.  Lung microbiome and cytokine profiles in different disease states of COPD: a cohort study , 2023, Scientific Reports.

[12]  L. Segal,et al.  Microbial inflammatory networks in bronchiectasis exacerbators with Pseudomonas aeruginosa. , 2023, Chest.

[13]  Y. Ke,et al.  The Lung Microbiome: A New Frontier for Lung and Brain Disease , 2023, International journal of molecular sciences.

[14]  A. Ceppe,et al.  Antibiotic Tolerance and Treatment Outcomes in Cystic Fibrosis Methicillin-Resistant Staphylococcus aureus Infections , 2022, Microbiology spectrum.

[15]  Marc Schneider,et al.  Probiotic Formulation Development and Local Application with Focus on Local Buccal, Nasal and Pulmonary Application , 2022, Current Nutraceuticals.

[16]  Z. Ren,et al.  The effect of the intratumoral microbiome on tumor occurrence, progression, prognosis and treatment , 2022, Frontiers in Immunology.

[17]  A. Consonni,et al.  Approaching the Gut and Nasal Microbiota in Parkinson’s Disease in the Era of the Seed Amplification Assays , 2022, Brain sciences.

[18]  M. Surette,et al.  Exploring the Cystic Fibrosis Lung Microbiome: Making the Most of a Sticky Situation , 2022, Journal of the Pediatric Infectious Diseases Society.

[19]  Luodan Yang,et al.  The Lung Microbiome: A Potential Target in Regulating Autoimmune Inflammation of the Brain , 2022, Neuroscience Bulletin.

[20]  X. Yi,et al.  The human lung microbiome—A hidden link between microbes and human health and diseases , 2022, iMeta.

[21]  Cuiming Zhu,et al.  The Beneficial Role of Probiotic Lactobacillus in Respiratory Diseases , 2022, Frontiers in Immunology.

[22]  B. Marsland,et al.  The lung-brain axis: A new frontier in host-microbe interactions. , 2022, Immunity.

[23]  B. G. Andrade,et al.  The role of respiratory microbiota in the protection against viral diseases: respiratory commensal bacteria as next-generation probiotics for COVID-19 , 2022, Bioscience of microbiota, food and health.

[24]  Z. Bagheri,et al.  Roles of Microbiota in Cancer: From Tumor Development to Treatment , 2022, Journal of oncology.

[25]  T. Gurley,et al.  Age-Related Changes in the Nasopharyngeal Microbiome Are Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Symptoms Among Children, Adolescents, and Young Adults , 2022, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[26]  Jianchao Wei,et al.  Targeting the Pulmonary Microbiota to Fight against Respiratory Diseases , 2022, Cells.

[27]  G. Maisetta,et al.  Lung-Directed Bacteriotherapy in Cystic Fibrosis: Could It Be an Option? , 2022, Antibiotics.

[28]  A. Flügel,et al.  The lung microbiome regulates brain autoimmunity , 2022, Nature.

[29]  A. Cervin,et al.  Nasal administration of a probiotic assemblage in allergic rhinitis: A randomised placebo‐controlled crossover trial , 2022, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[30]  G. Huffnagle,et al.  The Lung Microbiome during Health and Disease , 2021, International journal of molecular sciences.

[31]  Catherine Burke,et al.  Manipulation of the Upper Respiratory Microbiota to Reduce Incidence and Severity of Upper Respiratory Viral Infections: A Literature Review , 2021, Frontiers in Microbiology.

[32]  M. Pariano,et al.  Development and in vitro-in vivo performances of an inhalable indole-3-carboxaldehyde dry powder to target pulmonary inflammation and infection. , 2021, International journal of pharmaceutics.

[33]  R. Capasso,et al.  Involvement of Probiotics and Postbiotics in the Immune System Modulation , 2021, Biologics.

[34]  Gui-yuan Li,et al.  Lung microbiome alterations in NSCLC patients , 2021, Scientific Reports.

[35]  H. Wei,et al.  Enriched Opportunistic Pathogens Revealed by Metagenomic Sequencing Hint Potential Linkages between Pharyngeal Microbiota and COVID-19 , 2021, Virologica Sinica.

[36]  P. Zinzani,et al.  Brain dysfunction in COVID‐19 and CAR‐T therapy: cytokine storm‐associated encephalopathy , 2021, Annals of clinical and translational neurology.

[37]  M. López-Pérez,et al.  Nasopharyngeal Microbial Communities of Patients Infected With SARS-CoV-2 That Developed COVID-19 , 2020, bioRxiv.

[38]  Jing-quan Li,et al.  Microbiome dysbiosis in lung cancer: from composition to therapy , 2020, npj Precision Oncology.

[39]  S. Lebeer,et al.  Probiotic nasal spray development by spray drying. , 2020, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[40]  J. Madrenas,et al.  Intranasal Application of Lactococcus lactis W136 Is Safe in Chronic Rhinosinusitis Patients With Previous Sinus Surgery , 2020, Frontiers in Cellular and Infection Microbiology.

[41]  F. Inchingolo,et al.  The Human Respiratory System and its Microbiome at a Glimpse , 2020, Biology.

[42]  J. E. Aguilar-Toalá,et al.  Postbiotics and paraprobiotics: From concepts to applications. , 2020, Food research international.

[43]  Ran Wang,et al.  Microbiota Imbalance Contributes to COPD Deterioration by Enhancing IL-17a Production via miR-122 and miR-30a , 2020, Molecular therapy. Nucleic acids.

[44]  P. Gosset,et al.  Priming with intranasal lactobacilli prevents Pseudomonas aeruginosa acute pneumonia in mice , 2020, BMC microbiology.

[45]  Hideki Takahashi,et al.  The Ability of Respiratory Commensal Bacteria to Beneficially Modulate the Lung Innate Immune Response Is a Strain Dependent Characteristic , 2020, Microorganisms.

[46]  G. Héry-Arnaud,et al.  The Microbiome in Cystic Fibrosis Pulmonary Disease , 2020, Genes.

[47]  B. Gu,et al.  Microbiota dysbiosis in lung cancer: evidence of association and potential mechanisms , 2020, Translational lung cancer research.

[48]  R. Weichselbaum,et al.  Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling , 2020, The Journal of experimental medicine.

[49]  L. Delhaes,et al.  The Gut-Lung Axis in Health and Respiratory Diseases: A Place for Inter-Organ and Inter-Kingdom Crosstalks , 2020, Frontiers in Cellular and Infection Microbiology.

[50]  H. Xiong,et al.  Spray drying of Lactobacillus rhamnosus GG with calcium-containing protectant for enhanced viability , 2019 .

[51]  Chenxiao Hu,et al.  Microbiome Multi-Omics Network Analysis: Statistical Considerations, Limitations, and Opportunities , 2019, Front. Genet..

[52]  K. Koskinen,et al.  The microbiome of the upper respiratory tract in health and disease , 2019, BMC Biology.

[53]  A. Amedei,et al.  The lung microbiome: clinical and therapeutic implications , 2019, Internal and Emergency Medicine.

[54]  Tomasz P. Wypych,et al.  The influence of the microbiome on respiratory health , 2019, Nature Immunology.

[55]  H. Richardson,et al.  The microbiome in bronchiectasis , 2019, European Respiratory Review.

[56]  M. Surette,et al.  The effects of cycled inhaled aztreonam on the cystic fibrosis (CF) lung microbiome. , 2019, Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society.

[57]  J. Greenland,et al.  Parkinson’s Disease: Pathogenesis and Clinical Aspects , 2018 .

[58]  L. Drago,et al.  Probiotics Streptococcus salivarius 24SMB and Streptococcus oralis 89a interfere with biofilm formation of pathogens of the upper respiratory tract , 2018, BMC Infectious Diseases.

[59]  MingKun Li,et al.  Transcriptionally Active Lung Microbiome and Its Association with Bacterial Biomass and Host Inflammatory Status , 2018, mSystems.

[60]  G. DeLuca,et al.  Invited Review: From nose to gut – the role of the microbiome in neurological disease , 2018, Neuropathology and applied neurobiology.

[61]  S. Guglielmetti,et al.  Modulation of Pulmonary Microbiota by Antibiotic or Probiotic Aerosol Therapy: A Strategy to Promote Immunosurveillance against Lung Metastases. , 2018, Cell reports.

[62]  D. Descamps,et al.  Paradigms of Lung Microbiota Functions in Health and Disease, Particularly, in Asthma , 2018, Front. Physiol..

[63]  S. Lebeer,et al.  Enhancing the viability of Lactobacillus rhamnosus GG after spray drying and during storage. , 2017, International journal of pharmaceutics.

[64]  A. Cervin,et al.  Clinical efficacy of a topical lactic acid bacterial microbiome in chronic rhinosinusitis: A randomized controlled trial , 2017, Laryngoscope investigative otolaryngology.

[65]  W. T. Harris,et al.  Airway microbiota across age and disease spectrum in cystic fibrosis , 2017, European Respiratory Journal.

[66]  P. Sly,et al.  Streptococcus pneumoniae colonization of the nasopharynx is associated with increased severity during respiratory syncytial virus infection in young children , 2017, Respirology.

[67]  G. Jan,et al.  Spray drying of probiotics and other food-grade bacteria: A review , 2017 .

[68]  E. Pekkonen,et al.  Oral and nasal microbiota in Parkinson's disease. , 2017, Parkinsonism & related disorders.

[69]  Wouter A. A. de Steenhuijsen Piters,et al.  The microbiota of the respiratory tract: gatekeeper to respiratory health , 2017, Nature Reviews Microbiology.

[70]  M. Moffatt,et al.  Longitudinal assessment of sputum microbiome by sequencing of the 16S rRNA gene in non-cystic fibrosis bronchiectasis patients , 2017, PloS one.

[71]  M. Surette,et al.  Composition and immunological significance of the upper respiratory tract microbiota , 2016, FEBS letters.

[72]  You-Wen He,et al.  Lung inflammation stalls Th17-cell migration en route to the central nervous system during the development of experimental autoimmune encephalomyelitis. , 2016, International immunology.

[73]  R. Fuchs,et al.  Mechanism of human rhinovirus infections , 2016, Molecular and Cellular Pediatrics.

[74]  H. Smyth,et al.  Inhaled Biologics: From Preclinical to Product Approval. , 2016, Current pharmaceutical design.

[75]  J. Erb-Downward,et al.  Homeostasis and its disruption in the lung microbiome. , 2015, American journal of physiology. Lung cellular and molecular physiology.

[76]  S. Brix,et al.  Chronic obstructive pulmonary disease and asthma‐associated Proteobacteria, but not commensal Prevotella spp., promote Toll‐like receptor 2‐independent lung inflammation and pathology , 2015, Immunology.

[77]  J. Phillips Polio , 2015, Workplace health & safety.

[78]  Amy M. Sheflin,et al.  Cancer-Promoting Effects of Microbial Dysbiosis , 2014, Current Oncology Reports.

[79]  M. Caetano,et al.  T helper 17 cells play a critical pathogenic role in lung cancer , 2014, Proceedings of the National Academy of Sciences.

[80]  M. Lynch,et al.  Respiratory infection promotes T cell infiltration and amyloid-β deposition in APP/PS1 mice , 2014, Neurobiology of Aging.

[81]  E. Sanders,et al.  Viral and Bacterial Interactions in the Upper Respiratory Tract , 2013, PLoS pathogens.

[82]  R. Spang,et al.  T cells become licensed in the lung to enter the central nervous system , 2012, Nature.

[83]  F. Spertini,et al.  Intragastric and Intranasal Administration of Lactobacillus paracasei NCC2461 Modulates Allergic Airway Inflammation in Mice , 2012, International journal of inflammation.

[84]  K. Kristensson Microbes' roadmap to neurons , 2011, Nature Reviews Neuroscience.

[85]  John E. Scott,et al.  Alleviating Cancer Drug Toxicity by Inhibiting a Bacterial Enzyme , 2010, Science.

[86]  K Roos,et al.  Spray bacteriotherapy decreases middle ear fluid in children with secretory otitis media , 2008, Archives of Disease in Childhood.

[87]  J. Ager,et al.  The load of Chlamydia pneumoniae in the Alzheimer's brain varies with APOE genotype. , 2005, Microbial pathogenesis.

[88]  H. Scheiblauer,et al.  Interactions between bacteria and influenza A virus in the development of influenza pneumonia. , 1992, The Journal of infectious diseases.