{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T20:29:11Z","timestamp":1789504151479,"version":"build-2803163510"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006190","name":"Research and Development","doi-asserted-by":"publisher","award":["2021YFC2301000"],"award-info":[{"award-number":["2021YFC2301000"]}],"id":[{"id":"10.13039\/100006190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006190","name":"Research and Development","doi-asserted-by":"publisher","award":["2018ZX10201001"],"award-info":[{"award-number":["2018ZX10201001"]}],"id":[{"id":"10.13039\/100006190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006190","name":"Research and Development","doi-asserted-by":"publisher","award":["2018ZX10305410"],"award-info":[{"award-number":["2018ZX10305410"]}],"id":[{"id":"10.13039\/100006190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Influenza A virus (IAV)-induced dysbiosis may predispose to severe bacterial superinfections. Most studies have focused on the microbiota of single mucosal surfaces; consequently, the relationships between microbiota at different anatomic sites in IAV-infected mice have not been fully studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We characterized respiratory and gut microbiota using full-length 16S rRNA gene sequencing by Nanopore sequencers and compared the nasopharyngeal, oropharyngeal, lung and gut microbiomes in healthy and IAV-infected mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The oropharyngeal, lung and gut microbiota of healthy mice were dominated by <jats:italic>Lactobacillus<\/jats:italic> spp., while nasopharyngeal microbiota were comprised primarily of <jats:italic>Streptococcus<\/jats:italic> spp. However, the oropharyngeal, nasopharyngeal, lung, and gut microbiota of IAV-infected mice were dominated by <jats:italic>Pseudomonas, Escherichia<\/jats:italic>, <jats:italic>Streptococcus<\/jats:italic>, and <jats:italic>Muribaculum<\/jats:italic> spp., respectively. <jats:italic>Lactobacillus murinus<\/jats:italic> was identified as a biomarker and was reduced at all sites in IAV-infected mice. The microbiota composition of lung was more similar to that of the nasopharynx than the oropharynx in healthy mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings suggest that the main source of lung microbiota in mice differs from that of adults. Moreover, the similarity between the nasopharyngeal and lung microbiota was increased in IAV-infected mice. We found that IAV infection reduced the similarity between the gut and oropharyngeal microbiota. <jats:italic>L. murinus<\/jats:italic> was identified as a biomarker of IAV infection and may be an important target for intervention in post-influenza bacterial superinfections.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2023.1129690","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T05:25:21Z","timestamp":1677043521000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Topography of respiratory tract and gut microbiota in mice with influenza A virus infection"],"prefix":"10.3389","volume":"14","author":[{"given":"Qichao","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjiao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfeng","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peihan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leili","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbin","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"986","DOI":"10.3389\/fimmu.2018.00986","article-title":"Initial influenza virus replication can be limited in allergic asthma through rapid induction of type III interferons in respiratory epithelium","volume":"9","author":"An","year":"2018","journal-title":"Front. 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Immunol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1007\/s00125-017-4209-3","article-title":"Associations between hepatic miRNA expression, liver triacylglycerols and gut microbiota during metabolic adaptation to high-fat diet in mice","volume":"60","author":"Blasco-Baque","year":"2017","journal-title":"Diabetologia"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s40168-020-0785-4","article-title":"Self-reinoculation with fecal flora changes microbiota density and composition leading to an altered bile-acid profile in the mouse small intestine","volume":"8","author":"Bogatyrev","year":"2020","journal-title":"Microbiome."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1844","DOI":"10.1111\/jgh.14281","article-title":"Parasutterella, in association with irritable bowel syndrome and intestinal chronic inflammation","volume":"33","author":"Chen","year":"2018","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1038\/s41592-022-01520-4","article-title":"Emu: species-level microbial community profiling of full-length 16S rRNA Oxford Nanopore sequencing data","volume":"19","author":"Curry","year":"2022","journal-title":"Nat. Methods"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1136\/gutjnl-2018-317503","article-title":"Role of the microbiome in human development","volume":"68","author":"Dominguez-Bello","year":"2019","journal-title":"Gut"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/s41587-020-0548-6","article-title":"PICRUSt2 for prediction of metagenome functions","volume":"38","author":"Douglas","year":"2022","journal-title":"Nat. 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A."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1016\/S0140-6736(17)33293-2.27","article-title":"Estimates of global seasonal influenza-associated respiratory mortality: a modelling study","volume":"391","author":"Iuliano","year":"2018","journal-title":"Lancet"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"e01222","DOI":"10.1128\/mSystems.01222-20","article-title":"A 16S rRNA gene and draft genome database for the murine oral bacterial community","volume":"6","author":"Joseph","year":"2021","journal-title":"mSystems."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"2537","DOI":"10.1038\/s41467-020-16429-9","article-title":"Microbiome disturbance and resilience dynamics of the upper respiratory tract during influenza a virus infection","volume":"11","author":"Kaul","year":"2020","journal-title":"Nat. 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Microbiol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/s40168-020-00869-y","article-title":"Topography of the respiratory tract bacterial microbiota in cattle","volume":"8","author":"McMullen","year":"2020","journal-title":"Microbiome."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"3303","DOI":"10.3390\/ijms21093303","article-title":"The role of gut microbiome in psoriasis: oral administration of Staphylococcus aureus and streptococcus danieliae exacerbates skin inflammation of imiquimod-induced psoriasis-like dermatitis","volume":"21","author":"Okada","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s40168-018-0440-5","article-title":"Predominant gut lactobacillus murinus strain mediates anti-inflammaging effects in calorie-restricted mice","volume":"6","author":"Pan","year":"2018","journal-title":"Microbiome."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e01939","DOI":"10.1128\/mBio.01939-15","article-title":"Lambda interferon restructures the nasal microbiome and increases susceptibility to Staphylococcus aureus superinfection","volume":"7","author":"Planet","year":"2016","journal-title":"MBio"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"e50490","DOI":"10.3791\/50490","article-title":"Characterization of inflammatory responses during intranasal colonization with Streptococcus pneumoniae","volume":"83","author":"Puchta","year":"2014","journal-title":"J. Vis. Exp."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"14771","DOI":"10.1038\/srep14771","article-title":"Influence of H7N9 virus infection and associated treatment on human gut microbiota","volume":"5","author":"Qin","year":"2015","journal-title":"Sci. Rep."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1177\/15353702211057473","article-title":"Bacterial microbiota in upper respiratory tract of COVID-19 and influenza patients","volume":"247","author":"Rattanaburi","year":"2022","journal-title":"Exp. Biol. Med."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"5S","DOI":"10.1177\/0192623309353423","article-title":"Proliferative and nonproliferative lesions of the rat and mouse respiratory tract","volume":"37","author":"Renne","year":"2009","journal-title":"Toxicol. Pathol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1128\/CMR.00044-14","article-title":"Microbiology, genomics, and clinical significance of the Pseudomonas fluorescens species complex, an unappreciated colonizer of humans","volume":"27","author":"Scales","year":"2014","journal-title":"Clin. Microbiol. Rev."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"e0073420","DOI":"10.1128\/IAI.00734-20","article-title":"Influenza virus infection impairs the gut's barrier properties and favors secondary enteric bacterial infection through reduced production of short-chain fatty acids","volume":"89","author":"Sencio","year":"2021","journal-title":"Infect. Immun."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.chom.2015.07.003","article-title":"Inhibition of dectin-1 signaling ameliorates colitis by inducing lactobacillus-mediated regulatory T cell expansion in the intestine","volume":"18","author":"Tang","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1080\/15548627.2020.1725375","article-title":"Influenza a virus protein PB1-F2 impairs innate immunity by inducing mitophagy","volume":"17","author":"Wang","year":"2021","journal-title":"Autophagy"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"6362716","DOI":"10.1155\/2018\/6362716","article-title":"Distinct nasopharyngeal and oropharyngeal microbiota of children with influenza a virus compared with healthy children","volume":"2018","author":"Wen","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/nature24628","article-title":"Salt-responsive gut commensal modulates TH17 axis and disease","volume":"551","author":"Wilck","year":"2017","journal-title":"Nature"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"152190","DOI":"10.1016\/j.scitotenv.2021.152190","article-title":"Rapid absolute quantification of pathogens and ARGs by nanopore sequencing","volume":"809","author":"Yang","year":"2022","journal-title":"Sci. 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