{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T02:14:01Z","timestamp":1789611241952,"version":"build-2803163510"},"reference-count":74,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T00:00:00Z","timestamp":1650326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Otitis media (OM), defined as infection or inflammation of the middle ear (ME), remains a major public health problem worldwide. Cholesteatoma is a non-cancerous, cyst-like lesion in the ME that may be acquired due to chronic OM and cause disabling complications. Surgery is required for treatment, with high rates of recurrence. Current antibiotic treatments have been largely targeted to previous culturable bacteria, which may lead to antibiotic resistance or treatment failures. For this study, our goal was to determine the microbiota of cholesteatoma tissue in comparison with other ME tissues in patients with long-standing chronic OM. ME samples including cholesteatoma, granulation tissue, ME mucosa and discharge were collected from patients undergoing tympanomastoidectomy surgery for chronic OM. Bacteria were profiled by 16S rRNA gene sequencing in 103 ME samples from 53 patients. Respiratory viruses were also screened in 115 specimens from 45 patients. Differences in bacterial profiles (beta-diversity) and the relative abundances of individual taxa were observed between cholesteatoma and ME sample-types. Additionally, patient age was associated with differences in overall microbiota composition while numerous individual taxa were differentially abundant across age quartiles. No viruses were identified in screened ME samples. Biodiversity was moderately lower in cholesteatoma and ME discharge compared to ME mucosal tissues. We also present overall bacterial profiles of ME tissues by sample-type, age, cholesteatoma diagnosis and quinolone use, including prevalent bacterial taxa. Our findings will be useful for fine-tuning treatment protocols for cholesteatoma and chronic OM in settings with limited health care resources.<\/jats:p>","DOI":"10.3389\/fcimb.2022.746428","type":"journal-article","created":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T07:39:20Z","timestamp":1650353960000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Microbiota Associated With Cholesteatoma Tissue in Chronic Suppurative Otitis Media"],"prefix":"10.3389","volume":"12","author":[{"given":"Daniel N.","family":"Frank","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Pedrito M.","family":"Magno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen Joyce S.","family":"Velasco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tori C.","family":"Bootpetch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob Ephraim D.","family":"Salud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin Jer V.","family":"David","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron L.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eljohn C.","family":"Yee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather P.","family":"Dulnuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard B.","family":"Pyles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Alexeis C.","family":"Lacuata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeric L.","family":"Arbizo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Kofonow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Guce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin Michael D.","family":"Mendoza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles E.","family":"Robertson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel Martin S.","family":"Ilustre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra Nadine E.","family":"Chiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Long","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik A.","family":"Tongol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole D.","family":"Sacayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talitha Karisse L.","family":"Yarza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte M.","family":"Chiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regie Lyn P.","family":"Santos-Cortez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,19]]},"reference":[{"key":"B1","first-page":"129","article-title":"Comparative Efficacy and Safety of Ofloxacin and Polymyxin Otic Drops for Chronic Suppurative Otitis Media","volume":"1998","author":"Abes","year":"1998","journal-title":"Philipp J. Otolaryngol Head Neck Surg."},{"key":"B2","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1111\/j.1461-0248.2010.01552.x","article-title":"Navigating the Multiple Meanings of Beta Diversity: A Roadmap for the Practicing Ecologist","volume":"14","author":"Anderson","year":"2011","journal-title":"Ecol. Lett."},{"key":"B3","doi-asserted-by":"publisher","first-page":"20","DOI":"10.32412\/pjohns.v21i1-2.823","article-title":"Chronic Suppurative Otitis Media: Bacteriology and Drug Sensitivity Patterns at the Quirino Memorial Medical Center, (2004-2005): A Preliminary Study","volume":"21","author":"Ayson","year":"2006","journal-title":"Philipp J. Otolaryngol Head Neck Surg."},{"key":"B4","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1007\/s00405-012-2031-6","article-title":"Mental Health and Quality of Life in Patients With Chronic Otitis Media","volume":"270","author":"Bakir","year":"2013","journal-title":"Eur. Arch. Otorhinolaryngol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.01352","article-title":"Identification of Novel Genes and Biological Pathways That Overlap in Infectious and Nonallergic Diseases of the Upper and Lower Airways Using Network Analyses","volume":"10","author":"Baschal","year":"2019","journal-title":"Front. Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Statist Soc Ser. B."},{"key":"B7","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1002\/ijc.2910590405","article-title":"Human-Papillomavirus DNA in Cholesteatomas","volume":"59","author":"Bergmann","year":"1994","journal-title":"Int. J. Cancer"},{"key":"B8","doi-asserted-by":"publisher","first-page":"15035","DOI":"10.1038\/s41598-020-70498-w","article-title":"Multi-Omic Studies on Missense PLG Variants in Families With Otitis Media","volume":"10","author":"Bootpetch","year":"2020","journal-title":"Sci. Rep."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD013051.pub2","article-title":"Topical Antibiotics for Chronic Suppurative Otitis Media","volume":"1","author":"Brennan-Jones","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"B10","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1111\/jpc.12741","article-title":"Prevalence and Risk Factors for Parent-Reported Recurrent Otitis Media During Early Childhood in the Western Australian Pregnancy Cohort (Raine) Study","volume":"51","author":"Brennan-Jones","year":"2015","journal-title":"J. Paediatr. Child Health"},{"key":"B11","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/0165-5876(94)01080-h","article-title":"Role of Anaerobic Bacteria in Chronic Otitis Media and Cholesteatoma","volume":"31","author":"Brook","year":"1995","journal-title":"Int. J. Pediatr. Otorhinolaryngol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1513\/pats.201006-038RN","article-title":"Microbiology of Sinusitis","volume":"8","author":"Brook","year":"2011","journal-title":"Proc. Am. Thorac. Soc."},{"key":"B13","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1080\/14992027.2016.1250960","article-title":"Hearing Loss in Children With Otitis Media With Effusion: A Systematic Review","volume":"56","author":"Cai","year":"2017","journal-title":"Int. J. Audiol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1097\/MAO.0b013e31815882a6","article-title":"Probabilities of Ossicular Discontinuity in Chronic Suppurative Otitis Media Using Pure-Tone Audiometry","volume":"28","author":"Carrillo","year":"2007","journal-title":"Otol. Neurotol."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/desc.12588","article-title":"Not All Phonological Awareness Deficits Are Created Equal: Evidence From a Comparison Between Children With Otitis Media and Poor Readers","volume":"21","author":"Carroll","year":"2018","journal-title":"Dev. Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1001\/archotol.128.10.1129","article-title":"Evidence for Microbial Biofilms in Cholesteatomas","volume":"128","author":"Chole","year":"2002","journal-title":"Arch. Otolaryngol Head Neck Surg."},{"key":"B17","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1111\/vde.12886","article-title":"Antimicrobial Susceptibility Monitoring of Canine and Feline Skin and Ear Pathogens Isolated From European Veterinary Clinics: Results of the ComPath Surveillance Programme","volume":"31","author":"de Jong","year":"2020","journal-title":"Vet. Dermatol."},{"key":"B18","first-page":"58","article-title":"Microbial Flora in Chronic Otitis Media: Value of Ear Aspirate Culture Studies","volume":"1990","author":"del Rosario","year":"1990","journal-title":"Philipp J. Otolaryngol Head Neck Surg."},{"key":"B19","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1097\/INF.0000000000001442","article-title":"Macrolide and Clindamycin Resistance in Group a Streptococci Isolated From Children With Pharyngitis","volume":"36","author":"DeMuri","year":"2017","journal-title":"Pediatr. Infect. Dis. J."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2194","DOI":"10.1093\/bioinformatics\/btr381","article-title":"UCHIME Improves Sensitivity and Speed of Chimera Detection","volume":"27","author":"Edgar","year":"2011","journal-title":"Bioinformatics"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.798246","article-title":"The FUT2 Variant C.461G>A (P.Trp154*) Is Associated With Differentially Expressed Genes and Nasopharyngeal Microbiota Shifts in Patients With Otitis Media","volume":"11","author":"Elling","year":"2022","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B22","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1101\/gr.8.3.186","article-title":"Base-Calling of Automated Sequencer Traces Using Phred. II. Error Probabilities","volume":"8","author":"Ewing","year":"1998","journal-title":"Genome Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1101\/gr.8.3.175","article-title":"Base-Calling of Automated Sequencer Traces Using Phred. I. Accuracy Assessment","volume":"8","author":"Ewing","year":"1998","journal-title":"Genome Res."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067019","article-title":"ANOVA-Like Differential Expression (ALDEx) Analysis for Mixed Population RNA-Seq","volume":"8","author":"Fernandes","year":"2013","journal-title":"PloS One"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1186\/2049-2618-2-15","article-title":"Unifying the Analysis of High-Throughput Sequencing Datasets: Characterizing RNA-Seq, 16S rRNA Gene Sequencing and Selective Growth Experiments by Compositional Data Analysis","volume":"2","author":"Fernandes","year":"2014","journal-title":"Microbiome"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1864","DOI":"10.1001\/jama.2016.4151","article-title":"Prevalence of Inappropriate Antibiotic Prescriptions Among US Ambulatory Care Visits 2010-2011","volume":"315","author":"Fleming-Dutra","year":"2016","journal-title":"JAMA"},{"key":"B27","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1136\/jmedgenet-2020-106844","article-title":"Otitis Media Susceptibility and Shifts in the Head and Neck Microbiome Due to SPINK5 Variants","volume":"58","author":"Frank","year":"2020","journal-title":"J. Med. Genet"},{"key":"B28","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1159\/000101547","article-title":"Prevalence of Human Papillomavirus DNA in Cholesteatomas","volume":"69","author":"Franz","year":"2007","journal-title":"ORL J. Otorhinolaryngol Relat. Spec"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1016\/S0140-6736(20)30925-9","article-title":"Global Burden of 369 Diseases and Injuries in 204 Countries and Territories 1990-2019: A Systematic Analysis for the Global Burden of Disease Study 2019","volume":"396","year":"2020","journal-title":"Lancet"},{"key":"B30","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1016\/S0140-6736(21)00516-X","article-title":"Hearing Loss Prevalence and Years Lived With Disability 1990-2019: Findings From the Global Burden of Disease Study 2019","volume":"397","year":"2021","journal-title":"Lancet"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1870","DOI":"10.1001\/jamainternmed.2016.6625","article-title":"Frequency of First-Line Antibiotic Selection Among US Ambulatory Care Visits for Otitis Media, Sinusitis, and Pharyngitis","volume":"176","author":"Hersh","year":"2016","journal-title":"JAMA Intern. Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1097\/MAO.0000000000002168","article-title":"International Collaborative Assessment of the Validity of the EAONO-JOS Cholesteatoma Staging System","volume":"40","author":"James","year":"2019","journal-title":"Otol. Neurotol."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00456-19","article-title":"Examining the Evidence for an Adult Healthy Middle Ear Microbiome","volume":"4","author":"Jervis-Bardy","year":"2019","journal-title":"mSphere"},{"key":"B34","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.ijporl.2018.12.030","article-title":"Pathogen Reservoir Hypothesis Investigated by Analyses of the Adenotonsillar and Middle Ear Microbiota","volume":"118","author":"Johnston","year":"2019","journal-title":"Int. J. Pediatr. Otorhinolaryngol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1128\/mSystems.00056-21","article-title":"Case-Control Microbiome Study of Chronic Otitis Media With Effusion in Children Points at Streptococcus Salivarius as a Pathobiont-Inhibiting Species","volume":"6","author":"Jorissen","year":"2021","journal-title":"mSystems"},{"key":"B36","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1177\/0194599818772039","article-title":"Metagenomics Analysis of Bacterial Population of Tympanosclerotic Plaques and Cholesteatomas","volume":"159","author":"Kalcioglu","year":"2018","journal-title":"Otolaryngol Head Neck Surg."},{"key":"B37","doi-asserted-by":"publisher","first-page":"456","DOI":"10.3109\/00016489.2015.1129552","article-title":"Auditory Processing Abilities in Children With Chronic Otitis Media With Effusion","volume":"136","author":"Khavarghazalani","year":"2016","journal-title":"Acta Otolaryngol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"2568","DOI":"10.1002\/lary.23510","article-title":"How Long Is Long Enough to Follow Up Children After Cholesteatoma Surgery? A 29-Year Study","volume":"122","author":"Kuo","year":"2012","journal-title":"Laryngoscope"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/854024","article-title":"Updates and Knowledge Gaps in Cholesteatoma Research","volume":"2015","author":"Kuo","year":"2015","journal-title":"BioMed. Res. Int."},{"key":"B40","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast Gapped-Read Alignment With Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"B41","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s12866-018-1154-3","article-title":"A Microbiome Case-Control Study of Recurrent Acute Otitis Media Identified Potentially Protective Bacterial Genera","volume":"18","author":"Lappan","year":"2018","journal-title":"BMC Microbiol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1001\/jamaoto.2017.1068","article-title":"Prevalence of Hearing Loss Among Children 9 to 11 Years Old: The Generation R Study","volume":"143","author":"le Clercq","year":"2017","journal-title":"JAMA Otolaryngol Head Neck Surg."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioflm.2020.100041","article-title":"Oral Seeding and Niche-Adaptation of Middle Ear Biofilms in Health","volume":"3","author":"Lee","year":"2021","journal-title":"Biofilm"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/000348947208100102","article-title":"Acquired Cholesteatoma: Light and Electron Microscopic Observations","volume":"81","author":"Lim","year":"1972","journal-title":"Ann. Otol. Rhinol. Laryngol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"4083","DOI":"10.1128\/JCM.05010-11","article-title":"Comparison of the FilmArray Respiratory Panel and Prodesse Real-Time PCR Assays for Detection of Respiratory Pathogens","volume":"49","author":"Loeffelholz","year":"2011","journal-title":"J. Clin. Microbiol."},{"key":"B46","first-page":"7","article-title":"Molecular Biology of Cholesteatoma","volume":"55","author":"Maniu","year":"2014","journal-title":"Rom J. Morphol Embryol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"E371","DOI":"10.1002\/lary.26579","article-title":"Microbiomes of the Normal Middle Ear and Ears With Chronic Otitis Media","volume":"127","author":"Minami","year":"2017","journal-title":"Laryngoscope"},{"key":"B48","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1097\/MAO.0b013e31823dbc26","article-title":"Myringoplasty in Simple Chronic Otitis Media: Critical Analysis of Long-Term Results in a 1,000-Adult Patient Series","volume":"33","author":"Nardone","year":"2012","journal-title":"Otol. Neurotol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"2538","DOI":"10.1128\/JCM.01068-16","article-title":"Molecular Microbiological Profile of Chronic Suppurative Otitis Media","volume":"54","author":"Neeff","year":"2016","journal-title":"J. Clin. Microbiol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1097\/MOP.0000000000000184","article-title":"Importance of Viruses in Acute Otitis Media","volume":"27","author":"Nokso-Koivisto","year":"2015","journal-title":"Curr. Opin. Pediatr."},{"key":"B51","doi-asserted-by":"publisher","first-page":"S60","DOI":"10.5694\/j.1326-5377.2009.tb02929.x","article-title":"Complications of Otitis Media in Indigenous and Non-Indigenous Children","volume":"191","author":"O'Connor","year":"2009","journal-title":"Med. J. Aust."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1016\/j.ijporl.2015.05.029","article-title":"Tracking Tympanostomy Tube Outcomes in Pediatric Patients With Otitis Media Using an Electronic Database","volume":"79","author":"O'Niel","year":"2015","journal-title":"Int. J. Pediatr. Otorhinolaryngol"},{"key":"B53","unstructured":"OksanenJ.\n            BlanchetG.\n            FriendlyM.\n            KindtR.\n            LegendreP.\n            McGlinnD.\n          Vegan: Community Ecology Package. R Package Version 2.5-72019"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1093\/bioinformatics\/bts252","article-title":"SINA: Accurate High-Throughput Multiple Sequence Alignment of Ribosomal RNA Genes","volume":"28","author":"Pruesse","year":"2012","journal-title":"Bioinformatics"},{"key":"B55","doi-asserted-by":"publisher","first-page":"7188","DOI":"10.1093\/nar\/gkm864","article-title":"SILVA: A Comprehensive Online Resource for Quality Checked and Aligned Ribosomal RNA Sequence Data Compatible With ARB","volume":"35","author":"Pruesse","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"B56","doi-asserted-by":"publisher","first-page":"D590","DOI":"10.1093\/nar\/gks1219","article-title":"The SILVA Ribosomal RNA Gene Database Project: Improved Data Processing and Web-Based Tools","volume":"41","author":"Quast","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"B57","first-page":"197","article-title":"Notes on the Microbiology of Cholesteatoma: Clinical Findings and Treatment","volume":"29","author":"Ricciardiello","year":"2009","journal-title":"Acta Otorhinolaryngol Ital"},{"key":"B58","doi-asserted-by":"publisher","first-page":"3100","DOI":"10.1093\/bioinformatics\/btt526","article-title":"Explicet: Graphical User Interface Software for Metadata-Driven Management, Analysis and Visualization of Microbiome Data","volume":"29","author":"Robertson","year":"2013","journal-title":"Bioinformatics"},{"key":"B59","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.bjorl.2016.02.013","article-title":"Characteristics of 419 Patients With Acquired Middle Ear Cholesteatoma","volume":"83","author":"Rosito","year":"2017","journal-title":"Braz. J. Otorhinolaryngol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/j.ajhg.2018.09.010","article-title":"FUT2 Variants Confer Susceptibility to Familial Otitis Media","volume":"103","author":"Santos-Cortez","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"B61","doi-asserted-by":"publisher","first-page":"12","DOI":"10.32412\/pjohns.v22i1-2.789","article-title":"The Philippine National Ear Institute: Patient and Audiologic Profiles","volume":"22","author":"Santos-Cortez","year":"2007","journal-title":"Philipp J. Otolaryngol Head Neck Surg."},{"key":"B62","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/s40249-016-0189-7","article-title":"Middle Ear Microbiome Differences in Indigenous Filipinos With Chronic Otitis Media Due to a Duplication in the A2ML1 Gene","volume":"5","author":"Santos-Cortez","year":"2016","journal-title":"Infect. Dis. Poverty"},{"key":"B63","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.amjoto.2009.09.010","article-title":"Biofilms in Chronic Suppurative Otitis Media and Cholesteatoma: Scanning Electron Microscopy Findings","volume":"32","author":"Saunders","year":"2011","journal-title":"Am. J. Otolaryngol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"3219","DOI":"10.1128\/AEM.02810-10","article-title":"Assessing and Improving Methods Used in Operational Taxonomic Unit-Based Approaches for 16S rRNA Gene Sequence Analysis","volume":"77","author":"Schloss","year":"2011","journal-title":"Appl. Environ. Microbiol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"7479","DOI":"10.1016\/j.vaccine.2018.10.060","article-title":"Acute Otitis Media, Antimicrobial Prescriptions, and Medical Expenses Among Children in the United States During 2011-2016","volume":"36","author":"Suaya","year":"2018","journal-title":"Vaccine"},{"key":"B66","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1016\/j.jiac.2020.05.020","article-title":"The Seventh Nationwide Surveillance of Six Otorhinolaryngological Infectious Diseases and the Antimicrobial Susceptibility Patterns of the Isolated Pathogens in Japan","volume":"26","author":"Suzuki","year":"2020","journal-title":"J. Infect. Chemother."},{"key":"B67","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.jiac.2015.03.005","article-title":"Nationwide Surveillance of 6 Otorhinolaryngological Infectious Diseases and Antimicrobial Susceptibility Pattern in the Isolated Pathogens in Japan","volume":"21","author":"Suzuki","year":"2015","journal-title":"J. Infect. Chemother."},{"key":"B68","volume-title":"R: A Language and Environment for Statistical Computing, Vienna, Austria","author":"Team","year":"2019"},{"key":"B69","doi-asserted-by":"publisher","first-page":"e1182","DOI":"10.1542\/peds.2014-3141","article-title":"Cost-Effectiveness of Treatment of Acute Otorrhea in Children With Tympanostomy Tubes","volume":"135","author":"van Dongen","year":"2015","journal-title":"Pediatrics"},{"key":"B70","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.ijporl.2018.08.035","article-title":"Prospective Observational Case Series Evaluating Middle Ear Fluid and Tympanostomy Tubes Through Pyrosequencing","volume":"114","author":"Wang","year":"2018","journal-title":"Int. J. Pediatr. Otorhinolaryngol"},{"key":"B71","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1097\/MAO.0000000000002355","article-title":"Microbiome Analysis of Cholesteatoma by Gene Sequencing","volume":"40","author":"Weiss","year":"2019","journal-title":"Otol. Neurotol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"NP391","DOI":"10.1177\/0145561320923823","article-title":"Bacteriological Profile of Chronic Suppurative Otitis Media and Antibiotic Susceptibility in a Tertiary Care Hospital in Shanghai, China","volume":"100","author":"Xu","year":"2020","journal-title":"Ear Nose Throat J."},{"key":"B73","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.anaerobe.2015.05.006","article-title":"Fusobacterium Necrophorum and Other Fusobacterium Spp. Isolated From Head and Neck Infections: A 10-Year Epidemiology Study in an Academic Hospital","volume":"34","author":"Yusuf","year":"2015","journal-title":"Anaerobe"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0086397","article-title":"Risk Factors for Chronic and Recurrent Otitis Media-a Meta-Analysis","volume":"9","author":"Zhang","year":"2014","journal-title":"PloS One"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.746428\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T07:39:31Z","timestamp":1650353971000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.746428\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,19]]},"references-count":74,"alternative-id":["10.3389\/fcimb.2022.746428"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2022.746428","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,19]]},"article-number":"746428"}}