{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:57:48Z","timestamp":1792799868735,"version":"4.5.0"},"reference-count":85,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Pulmonary hypertension complicating chronic obstructive pulmonary disease (COPD-PH) has a worse prognosis than airflow limitation alone but its pathogenesis is thought to be primarily due to alveolar hypoxia affecting pulmonary circulation. Two observations are not fully explained by this model. First, the majority of exacerbations of COPD are infectious and there is a stable frequent-exacerbator phenotype that is not fully accounted for by spirometric severity. Second, the airways of COPD are not sterile. They are home to a resident microbial community that changes as the disease progresses and the gut microbial community also undergoes disease-associated changes. This review examines whether microbial factors actively contribute to pulmonary vascular remodelling or merely reflect advanced disease. Three candidate exposures are considered: chronic airway colonisation, dysbiosis of the airway and gut communities and recurrent infectious exacerbation. We then examine the virulence mechanisms and host-recognition pathways of non-typeable Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Pseudomonas aeruginosa, rhinovirus, influenza viruses, respiratory syncytial virus and SARS-CoV-2. We then trace the pathways linking microbial recognition to vascular injury: Toll-like receptor signalling and NF-\u03baB activation; interleukin-6, tumour necrosis factor-\u03b1 and interleukin-1\u03b2; endothelin-1 upregulation against nitric oxide depletion; reactive oxygen species and hypoxia-inducible factor signalling converging with hypoxic pulmonary vasoconstriction; and, along the gut\u2013lung axis, lipopolysaccharide translocation, trimethylamine N-oxide and depletion of short-chain fatty acid-producing taxa. Therapeutically, there is evidence and a vascular rationale for interventions that decrease exacerbation frequency. Pulmonary vasodilators have a sound physiological rationale, although their clinical efficacy is frequently limited by worsening ventilation\u2013perfusion mismatch. Current evidence supports biological plausibility rather than demonstrated causality: no direct longitudinal human study has established that microbial alterations or microbial exposure cause pulmonary vascular remodelling in COPD-PH. We identify study designs capable of directly testing this hypothesis.<\/jats:p>","DOI":"10.3390\/microorganisms14091954","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:21:21Z","timestamp":1788452481000},"page":"1954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Airway and Gut Dysbiosis, Infectious Exacerbations and Pulmonary Vascular Remodelling in COPD-Associated Pulmonary Hypertension: Microbial Mechanisms, Causal Uncertainty and Therapeutic Implications"],"prefix":"10.3390","volume":"14","author":[{"given":"Nilufar","family":"Akhmedova","sequence":"first","affiliation":[{"name":"Department of Nephrology and Hemodialysis, Bukhara State Medical Institute, Bukhara 200100, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8989-9706","authenticated-orcid":false,"given":"Gulomjon","family":"Kholov","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hemodialysis, Bukhara State Medical Institute, Bukhara 200100, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4481-9969","authenticated-orcid":false,"given":"Ulugbek","family":"Ochilov","sequence":"additional","affiliation":[{"name":"Interfaculty Department of Foreign Languages, Bukhara State University, Bukhara 200100, Uzbekistan"},{"name":"Department of Foreign Languages and Social Sciences, Asia International University, Bukhara 200100, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nodira","family":"Shonazarova","sequence":"additional","affiliation":[{"name":"Department of Internal Diseases No. 3, Samarkand State Medical University, Samarkand 140100, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otabek","family":"Yuldashev","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hemodialysis, Bukhara State Medical Institute, Bukhara 200100, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulkhayo","family":"Olimova","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hemodialysis, Bukhara State Medical Institute, Bukhara 200100, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Istamova","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hemodialysis, Bukhara State Medical Institute, Bukhara 200100, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sitora","family":"Mukhammadiyeva","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hemodialysis, Bukhara State Medical Institute, Bukhara 200100, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nozima","family":"Kenjayeva","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hemodialysis, Bukhara State Medical Institute, Bukhara 200100, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jahongir","family":"Sharipov","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hemodialysis, Bukhara State Medical Institute, Bukhara 200100, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","unstructured":"Global Initiative for Chronic Obstructive Lung Disease (2025). 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