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The human microbiome serves as a fundamental mediator of this shift, regulating immune homeostasis, barrier integrity and metabolic signaling across organs. While the lung maintains a characteristic low\u2010biomass microbiome in dynamic equilibrium, any disruption primes local and systemic immune responses contributing to disease. Beyond the well\u2010described gut\u2010lung axis, crosstalk between the lung and other distal organ systems is lesser recognized; however, increasingly acknowledged as a key under\u2010appreciated contributor to respiratory disease including extrapulmonary complications. This review synthesizes current established evidence on axial connectivity of the lung microbiome across the gut, brain, skin, heart, kidney, and liver, and finds that such crosstalk is predominantly, though not exclusively gut\u2010mediated. Direct lung\u2010organ interactions are described for several axes; however, they remain preliminary. Across these lung\u2010axial systems, common pathophysiological mechanisms emerge, including dysbiosis\u2010induced depletion of microbial metabolites, immunomodulation, and barrier perturbations, all linking pulmonary disease with neuroinflammation, gastrointestinal deficits, and cardiac, renal, hepatic, and dermatological abnormalities. We assess how therapeutic modulation of interorgan systems offers promising avenues for improved risk stratification and novel therapeutics. Recognizing microbiome\u2010mediated pulmonary\u2010organ crosstalk represents an emerging conceptual framework in respiratory medicine, repositioning microbial communities as key modulators of extrapulmonary disease.<\/jats:p>","DOI":"10.1002\/cph4.70269","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:56:21Z","timestamp":1789793781000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Axial Connectivity of the Lung Microbiome: A Review of Interorgan Crosstalk"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8710-4336","authenticated-orcid":false,"given":"Mathangi","family":"Palanivel","sequence":"first","affiliation":[{"name":"Lee Kong Chian School of Medicine Nanyang Technological University  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayanth Kumar","family":"Narayana","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine Nanyang Technological University  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0417-7607","authenticated-orcid":false,"given":"Sanjay H.","family":"Chotirmall","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine Nanyang Technological University  Singapore Singapore"},{"name":"Department of Respiratory and Critical Care Medicine Tan Tock Seng Hospital  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1159\/000508430","article-title":"COVID\u201019 Attacks the Kidney: Ultrastructural Evidence for the Presence of Virus in the Glomerular Epithelium","volume":"144","author":"Abbate M.","year":"2020","journal-title":"Nephron"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.biopsycho.2010.01.021","article-title":"HPA Axis, Respiration and the Airways in Stress\u2014A Review in Search of Intersections","volume":"84","author":"Abelson J. 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