{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T11:51:58Z","timestamp":1794484318576,"version":"4.9.1"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82102252"],"award-info":[{"award-number":["82102252"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82272245"],"award-info":[{"award-number":["82272245"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"crossref","award":["202440093, 2024ZZ1022"],"award-info":[{"award-number":["202440093, 2024ZZ1022"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Respir Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Despite advances in therapeutic strategies, acute respiratory distress syndrome (ARDS) mortality remains high. Growing evidence links respiratory microbiome composition to ARDS outcomes. This investigation sought to elucidate how colonizing bacteria and their metabolites influence ARDS pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Bronchoalveolar lavage fluid (BALF) from patients with pulmonary infections was analyzed by metagenomic next-generation sequencing (mNGS) to identify characteristic bacteria. Bacterial culture supernatants were analyzed by untargeted metabolomics (LC-MS) to identify metabolites. A murine ARDS model was established through intratracheal LPS instillation. Single-cell sequencing datasets from the GEO database were analyzed to reveal differential cell populations and functional alterations in murine ARDS. Potential molecular mechanisms were explored through molecular docking, RNA-seq analysis, Western boltting, and targeted gene knockdown in murine and cellular model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>R. mucilaginosa<\/jats:italic>\n                      demonstrated enrichment in patients without ARDS (nARDS). The bacterial culture supernatant conferred substantial protection in murine models, whereas viable bacteria showed minimal efficacy. LC-MS analysis identified indole-3-acetaldehyde (IAAld) as the predominant metabolite in the supernatant. Single-cell sequencing suggested that resident alveolar macrophages (RAMs) were pivotal cells in murine ARDS model. IAAld enhanced RAMs phagocytosis, facilitating neutrophil and LPS clearance. Mechanistic studies revealed that IAAld likely activated PXR signaling, promoted NRF2 nuclear translocation, and upregulated the phagocytosis-related gene\n                      <jats:italic>CD36<\/jats:italic>\n                      . Targeted PXR knockdown eliminated these protective effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The respiratory commensal\n                      <jats:italic>R. mucilaginosa<\/jats:italic>\n                      synthesizes IAAld, which\u2014independent of bacterial colonization per se\u2014ameliorates ARDS through PXR\/NRF2\/CD36 axis activation, thereby enhancing macrophage phagocytic function. These findings suggest that therapeutic targeting of microbial metabolites represents a novel ARDS treatment paradigm.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12931-026-03551-3","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T12:59:49Z","timestamp":1771505989000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Indole-acetaldehyde from Rothia mucilaginosa activates the PXR\/NRF2 axis to enhance alveolar macrophage phagocytosis and protect against ARDS"],"prefix":"10.1186","volume":"27","author":[{"given":"Wensi","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chujun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmei","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangni","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"3551_CR1","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1007\/s00134-012-2682-1","volume":"38","author":"ND Ferguson","year":"2012","unstructured":"Ferguson ND, Fan E, Camporota L, et al. The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material. Intensive Care Med. 2012;38:1573\u201382. https:\/\/doi.org\/10.1007\/s00134-012-2682-1.","journal-title":"Intensive Care Med Oct"},{"key":"3551_CR2","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1001\/jama.2016.6471","volume":"316","author":"G Bellani","year":"2016","unstructured":"Bellani G, Pham T, Laffey J, Investigators L-S, Group ET. Incidence of acute respiratory distress Syndrome\u2013Reply. JAMA. 2016;316:347. https:\/\/doi.org\/10.1001\/jama.2016.6471.","journal-title":"JAMA Jul 19"},{"key":"3551_CR3","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1007\/s00134-023-07050-7","volume":"49","author":"G Grasselli","year":"2023","unstructured":"Grasselli G, Calfee CS, Camporota L, et al. ESICM guidelines on acute respiratory distress syndrome: definition, phenotyping and respiratory support strategies. Intensive Care Med. 2023;49:727\u201359. https:\/\/doi.org\/10.1007\/s00134-023-07050-7.","journal-title":"Intensive Care Med Jul"},{"key":"3551_CR4","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1164\/rccm.202303-0558WS","volume":"209","author":"MA Matthay","year":"2024","unstructured":"Matthay MA, Arabi Y, Arroliga AC, et al. A new global definition of acute respiratory distress syndrome. Am J Respir Crit Care Med. 2024;209:37\u201347. https:\/\/doi.org\/10.1164\/rccm.202303-0558WS.","journal-title":"Am J Respir Crit Care Med Jan 1"},{"key":"3551_CR5","doi-asserted-by":"publisher","unstructured":"Merenstein C, Bushman FD, Collman RG. Alterations in the respiratory tract Microbiome in COVID-19: current observations and potential significance. Microbiome. 2022;10:165. https:\/\/doi.org\/10.1186\/s40168-022-01342-8.","DOI":"10.1186\/s40168-022-01342-8"},{"key":"3551_CR6","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41392-023-01722-y","volume":"9","author":"R Li","year":"2024","unstructured":"Li R, Li J, Zhou X. Lung microbiome: new insights into the pathogenesis of respiratory diseases. Signal Transduct Target Ther. 2024;9:19. https:\/\/doi.org\/10.1038\/s41392-023-01722-y.","journal-title":"Signal Transduct Target Ther"},{"key":"3551_CR7","doi-asserted-by":"publisher","unstructured":"Lipinksi JH, Ranjan P, Dickson RP, O\u2019Dwyer DN. The lung microbiome. Journal immunol (Baltimore, Md: 1950). 2024;212:1269\u201375. https:\/\/doi.org\/10.4049\/jimmunol.2300716","DOI":"10.4049\/jimmunol.2300716"},{"key":"3551_CR8","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1038\/nrmicro.2017.14","volume":"15","author":"WH Man","year":"2017","unstructured":"Man WH, de Steenhuijsen Piters WA, Bogaert D. The microbiota of the respiratory tract: gatekeeper to respiratory health. Nat Rev Microbiol. 2017;15:259\u201370. https:\/\/doi.org\/10.1038\/nrmicro.2017.14.","journal-title":"Nat Rev Microbiol"},{"key":"3551_CR9","doi-asserted-by":"publisher","first-page":"1666","DOI":"10.1164\/rccm.201912-2441OC","volume":"202","author":"GD Kitsios","year":"2020","unstructured":"Kitsios GD, Yang H, Yang L, et al. Respiratory tract dysbiosis is associated with worse outcomes in mechanically ventilated patients. Am J Respir Crit Care Med. 2020;202:1666\u201377. https:\/\/doi.org\/10.1164\/rccm.201912-2441OC.","journal-title":"Am J Respir Crit Care Med"},{"key":"3551_CR10","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1038\/s41564-021-00961-5","volume":"6","author":"I Sulaiman","year":"2021","unstructured":"Sulaiman I, Chung M, Angel L, et al. Microbial signatures in the lower airways of mechanically ventilated COVID-19 patients associated with poor clinical outcome. Nat Microbiol. 2021;6:1245\u201358. https:\/\/doi.org\/10.1038\/s41564-021-00961-5.","journal-title":"Nat Microbiol"},{"key":"3551_CR11","doi-asserted-by":"publisher","unstructured":"Rigauts C, Aizawa J, Taylor SL, et al. Rothia mucilaginosa is an anti-inflammatory bacterium in the respiratory tract of patients with chronic lung disease. Eur Respir J. 2022;59. https:\/\/doi.org\/10.1183\/13993003.01293-2021.","DOI":"10.1183\/13993003.01293-2021"},{"key":"3551_CR12","doi-asserted-by":"publisher","first-page":"10401","DOI":"10.1039\/d3fo04051h","volume":"27","author":"J Shen","year":"2023","unstructured":"Shen J, Wang S, Xia H, et al. Akkermansia muciniphila attenuated lipopolysaccharide-induced acute lung injury by modulating the gut microbiota and SCFAs in mice. Food Funct. 2023;27:14:10401\u201317. https:\/\/doi.org\/10.1039\/d3fo04051h.","journal-title":"Food Funct Nov"},{"key":"3551_CR13","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1136\/gutjnl-2023-329996","volume":"7","author":"S Xie","year":"2023","unstructured":"Xie S, Li J, Lyu F, et al. Novel tripeptide RKH derived from Akkermansia muciniphila protects against lethal sepsis. Gut. 2023;7:73:78\u201391. https:\/\/doi.org\/10.1136\/gutjnl-2023-329996.","journal-title":"Gut Dec"},{"key":"3551_CR14","doi-asserted-by":"publisher","unstructured":"Peng R, Song C, Gou S, et al. Gut clostridium sporogenes-derived Indole propionic acid suppresses osteoclast formation by activating pregnane X receptor. Pharmacol Res. 2024;202:107121. https:\/\/doi.org\/10.1016\/j.phrs.2024.107121.","DOI":"10.1016\/j.phrs.2024.107121"},{"key":"3551_CR15","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1056\/NEJMra1608077","volume":"10","author":"BT Thompson","year":"2017","unstructured":"Thompson BT, Chambers RC, Liu KD. Acute respiratory distress syndrome. N Engl J Med. 2017;10:377:562\u201372. https:\/\/doi.org\/10.1056\/NEJMra1608077.","journal-title":"N Engl J Med Aug"},{"key":"3551_CR16","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1111\/j.1600-065X.2011.01040.x","volume":"243","author":"KL Rock","year":"2011","unstructured":"Rock KL, Lai J-J, Kono H. Innate and adaptive immune responses to cell death. Immunological Reviews. 2011;243:191\u2013205. https:\/\/doi.org\/10.1111\/j.1600-065X.2011.01040.x.","journal-title":"Immunological Reviews 2011\/9\/\/"},{"key":"3551_CR17","doi-asserted-by":"publisher","unstructured":"Ren D, Ye X, Chen R, et al. Activation and evasion of inflammasomes during viral and microbial infection. Cell Mol Life Sci. 2025;82:56. https:\/\/doi.org\/10.1007\/s00018-025-05575-2.","DOI":"10.1007\/s00018-025-05575-2"},{"key":"3551_CR18","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.jare.2024.01.017","volume":"67","author":"Y Ye","year":"2025","unstructured":"Ye Y, Yang Q, Wei J, et al. RvD1 improves resident alveolar macrophage self-renewal via the ALX\/MAPK14\/S100A8\/A9 pathway in acute respiratory distress syndrome. J Adv Res. 2025;67:289\u201399. https:\/\/doi.org\/10.1016\/j.jare.2024.01.017.","journal-title":"J Adv Res 2025\/1\/\/"},{"key":"3551_CR19","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1146\/annurev-food-060721-025531","volume":"14","author":"D Amarakoon","year":"2023","unstructured":"Amarakoon D, Lee W-J, Tamia G, Lee S-H. Indole-3-Carbinol: Occurrence, Health-Beneficial Properties, and cellular molecular mechanisms. Annu Rev Food Sci Technol. 2023;14:347\u201366. https:\/\/doi.org\/10.1146\/annurev-food-060721-025531.","journal-title":"Annu Rev Food Sci Technol"},{"key":"3551_CR20","doi-asserted-by":"publisher","unstructured":"Shaheen N, Miao J, Xia B, Zhao Y, Zhao J. Multifaceted role of microbiota-derived indole-3-acetic acid in human diseases and its potential clinical application. FASEB journal: official publication of the federation of American societies for experimental biology. 2025;39:e70574. https:\/\/doi.org\/10.1096\/fj.202500295R.","DOI":"10.1096\/fj.202500295R"},{"key":"3551_CR21","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.1053\/j.gastro.2017.08.028","volume":"153","author":"S Nikolaus","year":"2017","unstructured":"Nikolaus S, Schulte B, Al-Massad N, et al. Increased Tryptophan metabolism is associated with activity of inflamm atory bowel diseases. Gastroenterol. 2017;153:1504\u2013e15162. https:\/\/doi.org\/10.1053\/j.gastro.2017.08.028.","journal-title":"Gastroenterol 2017\/12\/\/"},{"key":"3551_CR22","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1016\/j.ajpath.2018.01.011","volume":"188","author":"EE Alexeev","year":"2018","unstructured":"Alexeev EE, Lanis JM, Kao DJ, et al. Microbiota-Derived Indole metabolites promote human and murine intestinal homeostasis through regulation of Interleukin-10 receptor. Am J Pathol. 2018;188:1183\u201394. https:\/\/doi.org\/10.1016\/j.ajpath.2018.01.011.","journal-title":"Am J Pathol"},{"key":"3551_CR23","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1016\/j.molimm.2006.04.021","volume":"44","author":"AB Schote","year":"2007","unstructured":"Schote AB, Turner JD, Schiltz J, Muller CP. Nuclear receptors in human immune cells: expression and correlations. Mol Immunol. 2007;44:1436\u201345. https:\/\/doi.org\/10.1016\/j.molimm.2006.04.021.","journal-title":"Mol Immunol 2007\/2\/\/"},{"key":"3551_CR24","doi-asserted-by":"publisher","unstructured":"Dubrac S, Elentner A, Ebner S, Horejs-Hoeck J, Schmuth M. Modulation of T lymphocyte function by the pregnane X receptor. J Immunol (Baltimore, md: 1950). 2010;184:2949\u201357. https:\/\/doi.org\/10.4049\/jimmunol.0902151.","DOI":"10.4049\/jimmunol.0902151"},{"key":"3551_CR25","doi-asserted-by":"publisher","unstructured":"Zhao T, Zhong G, Wang Y, et al. Pregnane X receptor activation in liver macrophages protects against endotoxin-induced liver injury. Advanced science (Weinheim, Baden-Wurttemberg, Germany). 2024;11:e2308771. https:\/\/doi.org\/10.1002\/advs.202308771.","DOI":"10.1002\/advs.202308771"},{"key":"3551_CR26","doi-asserted-by":"publisher","first-page":"11624","DOI":"10.1038\/ncomms11624","volume":"7","author":"EH Kobayashi","year":"2016","unstructured":"Kobayashi EH, Suzuki T, Funayama R, et al. Nrf2 suppresses macrophage inflammatory response by blocking Proinflam matory cytokine transcription. Nat Commun. 2016;7:11624. https:\/\/doi.org\/10.1038\/ncomms11624.","journal-title":"Nat Commun 2016\/5\/23\/"},{"key":"3551_CR27","doi-asserted-by":"publisher","unstructured":"Feng Y, Shen J, Lin Z, Chen Z, Zhou M, Ma X. PXR activation relieves deoxynivalenol-induced liver oxidative stress via malat1 LncRNA m6A Demethylation. Advanced science (Weinheim, Baden-Wurttemberg, Germany). 2024;11:e2308742. https:\/\/doi.org\/10.1002\/advs.202308742","DOI":"10.1002\/advs.202308742"},{"key":"3551_CR28","doi-asserted-by":"publisher","unstructured":"Weber AA, Yang X, Mennillo E, et al. Triclosan administration to humanized UDP-glucuronosyltransferase 1 neonatal mice induces UGT1A1 through a dependence on PPAR\u03b1 and ATF4. J Biol Chem. 2024;300:107340. https:\/\/doi.org\/10.1016\/j.jbc.2024.107340.","DOI":"10.1016\/j.jbc.2024.107340"},{"key":"3551_CR29","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1038\/s41587-018-0006-x","volume":"37","author":"HC Metsky","year":"2019","unstructured":"Metsky HC, Siddle KJ, Gladden-Young A, et al. Capturing sequence diversity in metagenomes with comprehensive and scalable probe design. Nat Biotechnol. 2019;37:160\u20138. https:\/\/doi.org\/10.1038\/s41587-018-0006-x.","journal-title":"Nat Biotechnol 2019\/2\/\/"},{"key":"3551_CR30","doi-asserted-by":"publisher","unstructured":"Dickson RP, Singer BH, Newstead MW, et al. Enrichment of the lung Microbiome with gut bacteria in sepsis and the acute respiratory distress syndrome. Nat Microbiol. 2016;1:16113. https:\/\/doi.org\/10.1038\/nmicrobiol.2016.113.","DOI":"10.1038\/nmicrobiol.2016.113"},{"key":"3551_CR31","doi-asserted-by":"publisher","unstructured":"Matute-Bello G, Downey G, Moore BB et, al. An official American thoracic society workshop report: features and me asurements of experimental acute lung injury in animals. Am J Respir Cell Mol Biol. 2011;44:725\u2009\u2013\u200938. https:\/\/doi.org\/10.1165\/rcmb.2009-0210ST.","DOI":"10.1165\/rcmb.2009-0210ST"},{"key":"3551_CR32","doi-asserted-by":"publisher","unstructured":"Gallo K, Goede A, Preissner R, Gohlke B-O. SuperPred 3.0: drug classification and target prediction-a machine learning approach. Nucleic Acids Res. 2022;50:W726\u201331. https:\/\/doi.org\/10.1093\/nar\/gkac297.","DOI":"10.1093\/nar\/gkac297"},{"key":"3551_CR33","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.272re3","author":"RL Silverstein","year":"2009","unstructured":"Silverstein RL, Febbraio M. CD36, a scavenger receptor involved in immunity, metabolism, angiogenesis, and behavior. Sci Signal. 2009;2:re3. https:\/\/doi.org\/10.1126\/scisignal.272re3.","journal-title":"Sci Signal"},{"key":"3551_CR34","doi-asserted-by":"publisher","unstructured":"Jiang C, Liu Z, Hu R et, al. Inactivation of Rab11a GTPase in Macrophages Facilitates Phagocytosis of Apoptotic Neutrophils. J Immunol (Baltimore, Md: 1950). 2017;198:1660\u20131672. https:\/\/doi.org\/10.4049\/jimmunol.1601495.","DOI":"10.4049\/jimmunol.1601495"},{"key":"3551_CR35","doi-asserted-by":"publisher","unstructured":"Luo Z, Sheng Z, Hu L, et al. Targeted macrophage phagocytosis by Irg1\/itaconate axis improves the prognosis of intracerebral hemorrhagic stroke and peritonitis. EBioMedicine. 2024;101:104993. https:\/\/doi.org\/10.1016\/j.ebiom.2024.104993.","DOI":"10.1016\/j.ebiom.2024.104993"},{"key":"3551_CR36","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.immuni.2016.01.002","volume":"44","author":"B Luo","year":"2016","unstructured":"Luo B, Gan W, Liu Z, et al. Erythropoeitin signaling in macrophages promotes dying cell clearance and immune tolerance. Immun. 2016;44:287\u2013302. https:\/\/doi.org\/10.1016\/j.immuni.2016.01.002.","journal-title":"Immun 2016\/2\/16\/"},{"key":"3551_CR37","doi-asserted-by":"publisher","unstructured":"Bewley MA, Budd RC, Ryan E, et al. Opsonic phagocytosis in chronic obstructive pulmonary disease is enhanced by Nrf2 Agonists. Am J Respir Crit Care Med. 2018;198:739\u201350. https:\/\/doi.org\/10.1164\/rccm.201705-0903OC.","DOI":"10.1164\/rccm.201705-0903OC"},{"key":"3551_CR38","doi-asserted-by":"publisher","first-page":"L155","DOI":"10.1152\/ajplung.00449.2016","volume":"312","author":"H Zhao","year":"2017","unstructured":"Zhao H, Eguchi S, Alam A, Ma D. The role of nuclear factor-erythroid 2 related factor 2 (Nrf-2) in the protection against lung injury. Am J Physiology-Lung Cell Mol Physiol. 2017;312:L155\u201362. https:\/\/doi.org\/10.1152\/ajplung.00449.2016.","journal-title":"Am J Physiology-Lung Cell Mol Physiol"},{"key":"3551_CR39","doi-asserted-by":"publisher","first-page":"e00037","DOI":"10.1128\/mBio.00037-15","volume":"6","author":"CM Bassis","year":"2015","unstructured":"Bassis CM, Erb-Downward JR, Dickson RP, et al. Analysis of the upper respiratory tract microbiotas as the source of the lung and gastric microbiotas in healthy individuals. mBio. 2015;6:e00037. https:\/\/doi.org\/10.1128\/mBio.00037-15.","journal-title":"mBio"},{"key":"3551_CR40","doi-asserted-by":"publisher","unstructured":"Xu Q, Mei Z, Zha Q,et al. Characterization of Bronchoalveolar lavage fluid microbiota in acute exacerbations of bronchiectasis with non-tuberculous mycobacterial detection. Int J Infect Dis. 2024;146:107120. https:\/\/doi.org\/10.1016\/j.ijid.2024.107120.","DOI":"10.1016\/j.ijid.2024.107120"},{"key":"3551_CR41","doi-asserted-by":"publisher","unstructured":"Hai PD, Hoa LTV. Rothia mucilaginosa bacteremia after pneumonia in patient with cirrhosis: First report from Vietnam. New Microbes New Infec. 2022;47:100984. https:\/\/doi.org\/10.1016\/j.nmni.2022.100984.","DOI":"10.1016\/j.nmni.2022.100984"},{"key":"3551_CR42","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1177\/08968608221140227","volume":"43","author":"CW Ling","year":"2023","unstructured":"Ling CW, Sud K, Lee VW, et al. Treatment and outcomes of peritonitis due to Rothia species in patients on peritoneal dialysis: A systematic review and multicentre registry analysis. Perit Dial Int. 2023;43:220\u201330. https:\/\/doi.org\/10.1177\/08968608221140227.","journal-title":"Perit Dial Int 2023\/5\/\/"},{"key":"3551_CR43","doi-asserted-by":"publisher","unstructured":"Thurner L, Fadle N, Regitz E, et, al. B-cell receptor reactivity against Rothia mucilaginosa in nodular lymphocyte-predominant hodgkin lymphoma. haematol 2023\/5\/4\/. 2023;108:3347\u201358. https:\/\/doi.org\/10.3324\/haematol.2023.282698.","DOI":"10.3324\/haematol.2023.282698"},{"key":"3551_CR44","doi-asserted-by":"publisher","first-page":"e255","DOI":"10.1097\/INF.0000000000004322","volume":"43","author":"GJ Espinoza-Candelaria","year":"2024","unstructured":"Espinoza-Candelaria GJ, Mamauag E, Bukowinski A, Aldewereld Z. Successful treatment of a fulminant Rothia mucilaginosa central Nervou s system infection in an adolescent with T-Cell acute lymphoblastic Le Ukemia. Pediatr Infect Dis J. 2024;43:e255\u20136. https:\/\/doi.org\/10.1097\/INF.0000000000004322.","journal-title":"Pediatr Infect Dis J"},{"key":"3551_CR45","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1038\/s41586-023-06287-y","volume":"621","author":"J Major","year":"2023","unstructured":"Major J, Crotta S, Finsterbusch K, et al. Endothelial AHR activity prevents lung barrier disruption in viral infection. Nat. 2023;621:813\u201320. https:\/\/doi.org\/10.1038\/s41586-023-06287-y.","journal-title":"Nat 2023\/9\/"},{"key":"3551_CR46","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1124\/dmd.108.024190","volume":"37","author":"DB Buckley","year":"2009","unstructured":"Buckley DB, Klaassen CD. Induction of mouse UDP-glucuronosyltransferase mRNA expression in liver and intestine by activators of aryl-hydrocarbon receptor, constitutive Androstane receptor, pregnane X receptor, peroxisome proliferator-activated receptor alpha, and nuclear factor erythroid 2-related factor 2. Drug Metab Dispos. 2009;37:847\u201356. https:\/\/doi.org\/10.1124\/dmd.108.024190.","journal-title":"Drug Metab Dispos"},{"key":"3551_CR47","doi-asserted-by":"publisher","unstructured":"Aleksunes LM, Klaassen CD. Coordinated regulation of hepatic phase I and II drug-metabolizing genes and transporters using AhR-, CAR-, PXR-, PPAR\u03b1-, and Nrf2-null mice. Drug Metab Dispos. 2012;40:1366-79. https:\/\/doi.org\/10.1124\/dmd.112.045112.","DOI":"10.1124\/dmd.112.045112"}],"container-title":["Respiratory Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12931-026-03551-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-026-03551-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-026-03551-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:30:17Z","timestamp":1781634617000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12931-026-03551-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,19]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3551"],"URL":"https:\/\/doi.org\/10.1186\/s12931-026-03551-3","relation":{},"ISSN":["1465-993X"],"issn-type":[{"value":"1465-993X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,19]]},"assertion":[{"value":"29 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was conducted in accordance with the principles of International Council for Laboratory Animal Science. All procedures involving human participants were approved by the Ethics Committee of Shanghai Tenth People\u2019s Hospital (Approval No. SHSY-IEC-5.0\/24K11\/P01). All animal experiments were performed in compliance with the Guide for the Care and Use of Laboratory Animals (NIH) and approved by the corresponding institutional ethics committee (Approval No. 25KN297).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"112"}}