{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T01:51:27Z","timestamp":1781747487340,"version":"3.54.5"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF) Grant funded by the Ministry of Education, Science, and Technology","award":["2022R1C1C1002741"],"award-info":[{"award-number":["2022R1C1C1002741"]}]},{"name":"National Research Foundation of Korea (NRF) Grant funded by the Ministry of Education, Science, and Technology","award":["2020R1F1A1076570"],"award-info":[{"award-number":["2020R1F1A1076570"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Although gastroesophageal reflux has been recognized as one of the risk factors of nontuberculous mycobacterial pulmonary disease (NTM-PD) progression, the effect of reflux on the lower respiratory tract microbiota has not been studied in detail. We investigated the composition of the lower respiratory tract microbiota in patients with clinically suspected NTM-PD, comparing them based on the presence of reflux. Forty-seven patients suspected of having NTM-PD were enrolled and assigned according to presence of reflux (n = 22) and non- reflux (n = 25). We performed a pepsin ELISA assay to identify the presence of reflux and 16S ribosomal RNA gene amplicon sequencing to evaluate the microbiota in bronchoalveolar lavage fluid. There were no significant differences in the diversity or composition of the lower respiratory microbiota between the NTM-PD and non-NTM-PD groups. Bacterial richness was observed in the non-reflux group than in the reflux group [<jats:italic>P<\/jats:italic> = 0.03] and a cluster in the reflux group was observed. The reflux group showed a predominance for <jats:italic>Pseudomonas aeruginosa<\/jats:italic> or <jats:italic>Staphylococcus aureus<\/jats:italic> among the NTM-PD group and for <jats:italic>P<\/jats:italic>. <jats:italic>aeruginosa<\/jats:italic>, <jats:italic>Haemophilus influenzae<\/jats:italic>, <jats:italic>Klebsiella pneumoniae<\/jats:italic>, or <jats:italic>Eikenella<\/jats:italic> species among the non-NTM-PD group. The non-reflux groups presented diverse patterns. A linear discriminant analysis and volcano plot demonstrated that <jats:italic>P<\/jats:italic>. <jats:italic>aeruginosa<\/jats:italic>, <jats:italic>H<\/jats:italic>. <jats:italic>haemolyticus<\/jats:italic>, <jats:italic>Selenomonas artemidis<\/jats:italic>, and <jats:italic>Dolosigranulum pigrum<\/jats:italic> were specifically associated with the NTM-PD reflux group, while <jats:italic>P<\/jats:italic>. <jats:italic>aeruginosa<\/jats:italic> was specifically associated with the non-NTM-PD reflux group. These observations confirm that the lower respiratory microbiota is consistently altered by reflux but not in NTM-PD.<\/jats:p>","DOI":"10.1371\/journal.pone.0309446","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T17:44:49Z","timestamp":1724867089000},"page":"e0309446","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Lower respiratory tract microbiota in patients with clinically suspected nontuberculous mycobacterial pulmonary disease according to the presence of gastroesophageal reflux"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8750-4257","authenticated-orcid":true,"given":"Eun Jeong","family":"Won","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Jeong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moon-Ju","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Jong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Joon","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Ok","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5121-4488","authenticated-orcid":true,"given":"Yong-Soo","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,8,28]]},"reference":[{"issue":"1","key":"pone.0309446.ref001","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ccm.2014.10.002","article-title":"Epidemiology of human pulmonary infection with nontuberculous mycobacteria: a review","volume":"36","author":"DR Prevots","year":"2015","journal-title":"Clin Chest Med"},{"issue":"6","key":"pone.0309446.ref002","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1378\/chest.06-2280","article-title":"Prevalence of gastroesophageal reflux disease in patients with nontuberculous mycobacterial lung disease","volume":"131","author":"WJ Koh","year":"2007","journal-title":"Chest"},{"issue":"4","key":"pone.0309446.ref003","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1378\/chest.06-1906","article-title":"Gastroesophageal reflux disease, acid suppression, and Mycobacterium avium complex pulmonary disease","volume":"131","author":"RM Thomson","year":"2007","journal-title":"Chest"},{"issue":"2","key":"pone.0309446.ref004","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.chest.2022.08.2228","article-title":"Gastroesophageal Reflux Disease Increases Susceptibility to Nontuberculous Mycobacterial Pulmonary Disease","volume":"163","author":"Y Kim","year":"2023","journal-title":"Chest"},{"issue":"1","key":"pone.0309446.ref005","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.02287-16","article-title":"Bacterial Topography of the Healthy Human Lower Respiratory Tract","volume":"8","author":"RP Dickson","year":"2017","journal-title":"mBio"},{"issue":"7","key":"pone.0309446.ref006","doi-asserted-by":"crossref","first-page":"766","DOI":"10.3390\/antibiotics10070766","article-title":"Systems Biology and Bile Acid Signalling in Microbiome-Host Interactions in the Cystic Fibrosis Lung","volume":"10","author":"DF Woods","year":"2021","journal-title":"Antibiotics (Basel)"},{"issue":"3","key":"pone.0309446.ref007","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/S2213-2600(14)70028-1","article-title":"Towards an ecology of the lung: new conceptual models of pulmonary microbiology and pneumonia pathogenesis","volume":"2","author":"RP Dickson","year":"2014","journal-title":"Lancet Respir Med"},{"key":"pone.0309446.ref008","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/1471-2180-14-130","article-title":"Polymicrobial airway bacterial communities in adult bronchiectasis patients","volume":"14","author":"P Purcell","year":"2014","journal-title":"BMC Microbiol"},{"issue":"6","key":"pone.0309446.ref009","doi-asserted-by":"crossref","first-page":"e11044","DOI":"10.1371\/journal.pone.0011044","article-title":"Airway microbiota and pathogen abundance in age-stratified cystic fibrosis patients","volume":"5","author":"MJ Cox","year":"2010","journal-title":"PLoS One"},{"issue":"1","key":"pone.0309446.ref010","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s40168-020-00810-3","article-title":"Lung function and microbiota diversity in cystic fibrosis","volume":"8","author":"L Cuthbertson","year":"2020","journal-title":"Microbiome"},{"issue":"2","key":"pone.0309446.ref011","doi-asserted-by":"crossref","first-page":"74","DOI":"10.4046\/trd.2016.79.2.74","article-title":"Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease: Clinicians\u2019 Perspectives","volume":"79","author":"YJ Ryu","year":"2016","journal-title":"Tuberc Respir Dis (Seoul)"},{"issue":"4","key":"pone.0309446.ref012","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1093\/cid\/ciaa1125","article-title":"Treatment of Nontuberculous Mycobacterial Pulmonary Disease: An Official ATS\/ERS\/ESCMID\/IDSA Clinical Practice Guideline","volume":"71","author":"CL Daley","year":"2020","journal-title":"Clin Infect Dis"},{"issue":"2","key":"pone.0309446.ref013","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.jpedsurg.2005.11.002","article-title":"Pepsin in bronchoalveolar lavage fluid: a specific and sensitive method of diagnosing gastro-oesophageal reflux-related pulmonary aspiration","volume":"41","author":"S Farrell","year":"2006","journal-title":"J Pediatr Surg"},{"issue":"3","key":"pone.0309446.ref014","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1620\/tjem.246.147","article-title":"Association between Pepsin in Bronchoalveolar Lavage Fluid and Prognosis of Chronic Fibrosing Interstitial Lung Disease","volume":"246","author":"Y Kim","year":"2018","journal-title":"Tohoku J Exp Med"},{"issue":"42","key":"pone.0309446.ref015","doi-asserted-by":"crossref","first-page":"7340","DOI":"10.3748\/wjg.v27.i42.7340","article-title":"Gut microbiome composition can predict the response to nivolumab in advanced hepatocellular carcinoma patients","volume":"27","author":"MW Chung","year":"2021","journal-title":"World J Gastroenterol"},{"issue":"1","key":"pone.0309446.ref016","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3390\/microorganisms10010034","article-title":"Gut Microbiome Profiles in Colonizations with the Enteric Protozoa Blastocystis in Korean Populations","volume":"10","author":"MJ Kim","year":"2021","journal-title":"Microorganisms"},{"key":"pone.0309446.ref017","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.3389\/fmicb.2019.02407","article-title":"Rarefaction, Alpha Diversity, and Statistics","volume":"10","author":"AD Willis","year":"2019","journal-title":"Front Microbiol"},{"issue":"6","key":"pone.0309446.ref018","doi-asserted-by":"crossref","first-page":"R60","DOI":"10.1186\/gb-2011-12-6-r60","article-title":"Metagenomic biomarker discovery and explanation","volume":"12","author":"N Segata","year":"2011","journal-title":"Genome Biol"},{"issue":"6","key":"pone.0309446.ref019","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/s41587-020-0548-6","article-title":"PICRUSt2 for prediction of metagenome functions","volume":"38","author":"GM Douglas","year":"2020","journal-title":"Nat. Biotechnol"},{"issue":"4","key":"pone.0309446.ref020","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.trsl.2012.02.005","article-title":"The microbiome of the lung","volume":"160","author":"JM Beck","year":"2012","journal-title":"Transl Res"},{"issue":"51","key":"pone.0309446.ref021","doi-asserted-by":"crossref","first-page":"20529","DOI":"10.1073\/pnas.0709804104","article-title":"Molecular identification of bacteria in bronchoalveolar lavage fluid from children with cystic fibrosis","volume":"104","author":"JK Harris","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"pone.0309446.ref022","doi-asserted-by":"crossref","first-page":"1602086","DOI":"10.1183\/13993003.02086-2016","article-title":"The microbiome in respiratory medicine: current challenges and future perspectives","volume":"49","author":"R Faner","year":"2017","journal-title":"Eur Respir J"},{"issue":"10","key":"pone.0309446.ref023","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1038\/s41590-019-0451-9","article-title":"The influence of the microbiome on respiratory health","volume":"20","author":"TP Wypych","year":"2019","journal-title":"Nat Immunol"},{"issue":"4","key":"pone.0309446.ref024","doi-asserted-by":"crossref","first-page":"1800810","DOI":"10.1183\/13993003.00810-2018","article-title":"Evaluation of the airway microbiome in nontuberculous mycobacteria disease","volume":"52","author":"I Sulaiman","year":"2018","journal-title":"Eur Respir J"},{"issue":"5","key":"pone.0309446.ref025","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1111\/resp.12536","article-title":"Possible role of anaerobes in the pathogenesis of nontuberculous mycobacterial infection","volume":"20","author":"K Yamasaki","year":"2015","journal-title":"Respirology"},{"issue":"2","key":"pone.0309446.ref026","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1017\/S0007114519000680","article-title":"Gut Prevotella as a possible biomarker of diet and its eubiotic versus dysbiotic roles: a comprehensive literature review","volume":"122","author":"G Precup","year":"2019","journal-title":"Br J Nutr"},{"key":"pone.0309446.ref027","article-title":"Fretibacterium species to Fusobacterium periodonticum ratio as a potential biomarker of periodontitis based on salivary microbiome profiling","author":"EJ Oh","year":"2024","journal-title":"Ann Lab Med"},{"issue":"1","key":"pone.0309446.ref028","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41392-023-01722-y","article-title":"Lung microbiome: new insights into the pathogenesis of respiratory diseases","volume":"9","author":"R Li","year":"2024","journal-title":"Signal Transduct Target Ther"},{"issue":"4","key":"pone.0309446.ref029","doi-asserted-by":"crossref","first-page":"1701086","DOI":"10.1183\/13993003.01086-2017","article-title":"Chronic but not intermittent infection with Pseudomonas aeruginosa is associated with global changes of the lung microbiome in cystic fibrosis","volume":"50","author":"S Boutin","year":"2017","journal-title":"Eur Respir J"},{"issue":"1","key":"pone.0309446.ref030","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/j.1752-4571.2008.00059.x","article-title":"Evolutionary ecology of microbial wars: within-host competition and (incidental) virulence","volume":"2","author":"SP Brown","year":"2009","journal-title":"Evol Appl"},{"issue":"9","key":"pone.0309446.ref031","doi-asserted-by":"crossref","first-page":"e45001","DOI":"10.1371\/journal.pone.0045001","article-title":"The adult cystic fibrosis airway microbiota is stable over time and infection type, and highly resilient to antibiotic treatment of exacerbations","volume":"7","author":"AA Fodor","year":"2012","journal-title":"PLoS One"},{"issue":"5","key":"pone.0309446.ref032","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1189\/jlb.3MR0316-106R","article-title":"A tale of two sites: how inflammation can reshape the microbiomes of the gut and lungs","volume":"100","author":"BS Scales","year":"2016","journal-title":"J Leukoc Biol"},{"issue":"2","key":"pone.0309446.ref033","doi-asserted-by":"crossref","first-page":"e0148534","DOI":"10.1371\/journal.pone.0148534","article-title":"Assessment of the Microbial Constituents of the Home Environment of Individuals with Cystic Fibrosis (CF) and Their Association with Lower Airways Infections","volume":"11","author":"A Heirali","year":"2016","journal-title":"PLoS One"},{"issue":"10150","key":"pone.0309446.ref034","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/S0140-6736(18)31767-7","article-title":"Advances in bronchiectasis: endotyping, genetics, microbiome, and disease heterogeneity","volume":"392","author":"PA Flume","year":"2018","journal-title":"Lancet"},{"issue":"25","key":"pone.0309446.ref035","doi-asserted-by":"crossref","first-page":"3559","DOI":"10.1021\/acs.biochem.6b00409","article-title":"Structural and functional characterization of aerobactin synthetase IucA from a hypervirulent pathotype of Klebsiella pneumoniae","volume":"55","author":"DC Bailey","year":"2016","journal-title":"Biochemistry"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0309446","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T17:45:33Z","timestamp":1724867133000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0309446"}},"subtitle":[],"editor":[{"given":"Frederick","family":"Quinn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,8,28]]},"references-count":35,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0309446","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,28]]}}}