{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T17:16:38Z","timestamp":1784740598831,"version":"3.55.0"},"reference-count":90,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>The lower airways are a dynamic environment where physical, microbial, and molecular factors intersect to regulate respiratory health and disease. The muco-microbiotic (MuMi) layer, composed of mucus, resident microbes, and extracellular vesicles (EVs), is not just a passive barrier but also an active site for host\u2013microbe communication. This layer integrates epithelial cell biology, microbial activity, and immune responses within the bronchial environment. New transcriptomic and metatranscriptomic technologies show that it is not only which microbes are present but also their gene activity that closely links to airway inflammation and disease. EV-associated RNAs from both host and microbial cells act as key messengers, influencing epithelial responses, immune activity, mucus properties, and microbial behaviour. This review highlights evidence that positions the MuMi layer as central to understanding lower airway disease, particularly asthma and chronic obstructive pulmonary disease (COPD). Distinct gene expression programs and biomarker profiles, such as exhaled nitric oxide, may reflect different disease mechanisms even in cases with similar clinical features, such as eosinophilia. Multi-omic approaches focused on the MuMi layer enable better disease classification, biomarker discovery, and therapy selection. By putting the MuMi interface at the core of precision pulmonology, we provide a framework for advancing personalised care in chronic respiratory diseases.<\/jats:p>","DOI":"10.3390\/biology15090684","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:34:42Z","timestamp":1777458882000},"page":"684","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Muco-Microbiotic Layer in Respiratory Pathophysiology: Integrating Transcriptomics, Inflammation Phenotypes, and Clinical Biomarkers in Precision Pulmonology"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5888-8781","authenticated-orcid":false,"given":"Claudio","family":"Candia","sequence":"first","affiliation":[{"name":"Istituti Clinici Scientifici Maugeri IRCCS, Pulmonary Rehabilitation Unit of Telese Terme Institute, 82037 Telese Terme, Italy"},{"name":"Department of Biomedicine, 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0553-536X","authenticated-orcid":false,"given":"Domiziana","family":"Picone","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2131-563X","authenticated-orcid":false,"given":"Giuseppa","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8260-8471","authenticated-orcid":false,"given":"Celeste","family":"Caruso Bavisotto","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Bucchieri","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1986-1495","authenticated-orcid":false,"given":"Silvestro Ennio","family":"D\u2019Anna","sequence":"additional","affiliation":[{"name":"Istituti Clinici Scientifici Maugeri IRCCS, Pulmonary Rehabilitation Unit of Telese Terme Institute, 82037 Telese Terme, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4618-4963","authenticated-orcid":false,"given":"Alessandro","family":"Pitruzzella","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6751-9921","authenticated-orcid":false,"given":"Mauro","family":"Maniscalco","sequence":"additional","affiliation":[{"name":"Istituti Clinici Scientifici Maugeri IRCCS, Pulmonary Rehabilitation Unit of Telese Terme Institute, 82037 Telese Terme, Italy"},{"name":"Department of Advanced Biomedical Sciences, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Bonaventura","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9497-5612","authenticated-orcid":false,"given":"Stefano","family":"Burgio","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Kore 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