{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T08:20:42Z","timestamp":1791015642622,"version":"4.1.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T00:00:00Z","timestamp":1631577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003354","name":"Garnett Passe and Rodney Williams Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003354","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Chronic rhinosinusitis (CRS) is a globally prevalent inflammatory condition of the paranasal sinuses which severely impairs patients\u2019 quality of life. An animal model of unilateral sinusitis by transient sinus occlusion has been described previously in rabbits. The aim of this study was to characterise the sinusitis rabbit model by investigating temporal and bilateral changes in the bacterial community and mucosal inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Development of sinusitis was achieved by endoscopically placing Merocel<jats:italic><jats:sup>\u00ae<\/jats:sup><\/jats:italic>, a sterile nasal packing material, in the left middle meatus of six New Zealand white rabbits for four weeks. After a total period of 14 weeks, rabbits were assessed for sinusitis by endoscopic examination, magnetic resonance imaging (MRI) and histology. Swabs from the left and right middle meatus were obtained for bacterial community analysis at three time points (week 0, week 4, week 14) during the study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Endoscopic evaluation showed unilateral inflammation in all animals examined after the 4-week blocking period and at week 14. Notably, inflammatory changes were also seen in the contralateral sinus of all animals at week 4. MRI images demonstrated unilateral sinus opacification at week 4 in two rabbits, and partial unilateral sinus opacification at week 14 in one rabbit only. Histological analyses revealed substantial spatial heterogeneity of mucosal inflammation with inconsistent findings across all animals. No significant differences in mucosal inflammatory markers (such as goblet cell hyperplasia, epithelial denudation and oedema) could be identified between nostrils at week 14. The bacterial community in the rabbit sinuses was heavily dominated by <jats:italic>Helicobacter<\/jats:italic> at week 0 (baseline). At the end of the blocking period (week 4), bacterial alpha and beta diversity were significantly increased in both nostrils. The bacterial community composition at week 14 had primarily returned to baseline, reflecting the endoscopic and radiological results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study reaffirmed the ability for development of sinusitis without inoculation of any pathogens in a rabbit model. We were able to demonstrate bilateral sinonasal mucosal inflammation, by inducing unilateral sinus blockage, which resulted in significant changes to the sinonasal bacterial community. These findings may explain some of the clinical observations seen in CRS and warrant further research to reveal potential implications for its therapeutic management.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2021.585625","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T05:55:00Z","timestamp":1631598900000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Unilateral Intervention in the Sinuses of Rabbits Induces Bilateral Inflammatory and Microbial Changes"],"prefix":"10.3389","volume":"11","author":[{"given":"Christian A.","family":"Lux","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Johnston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Waldvogel-Thurlow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Dassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard G.","family":"Douglas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do-Yeon","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristi","family":"Biswas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14811","article-title":"The Comparative Immunology of Wild and Laboratory Mice, Mus Musculus Domesticus","volume":"8","author":"Abolins","year":"2017","journal-title":"Nat. Commun."},{"key":"B2","doi-asserted-by":"publisher","first-page":"151ra124","DOI":"10.1126\/scitranslmed.3003783","article-title":"Sinus Microbiome Diversity Depletion and Corynebacterium Tuberculostearicum Enrichment Mediates Rhinosinusitis","volume":"4","author":"Abreu","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1016\/j.jaci.2018.03.004","article-title":"Endotype-Driven Care Pathways in Patients With Chronic Rhinosinusitis","volume":"141","author":"Bachert","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.00134","article-title":"The Nasal Microbiota in Health and Disease: Variation Within and Between Subjects","volume":"9","author":"Biswas","year":"2015","journal-title":"Front. Microbiol."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00504","article-title":"Differentially Regulated Host Proteins Associated With Chronic Rhinosinusitis Are Correlated With the Sinonasal Microbiome","volume":"7","author":"Biswas","year":"2017","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-13-210","article-title":"The Microbiome of Chronic Rhinosinusitis: Culture, Molecular Diagnostics and Biofilm Detection","volume":"13","author":"Boase","year":"2013","journal-title":"BMC Infect. Dis."},{"key":"B7","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1002\/alr.20066","article-title":"A Sheep Model to Investigate the Role of Fungal Biofilms in Sinusitis: Fungal and Bacterial Synergy","volume":"1","author":"Boase","year":"2011","journal-title":"Int. Forum Allergy Rhinol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"7926","DOI":"10.1038\/s41598-018-26327-2","article-title":"Chronic Rhinosinusitis With Nasal Polyps Is Characterized by Dysbacteriosis of the Nasal Microbiota","volume":"8","author":"Chalermwatanachai","year":"2018","journal-title":"Sci. Rep."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1093\/jac\/dkm087","article-title":"Evaluation of the In Vivo Efficacy of Topical Tobramycin Against Pseudomonas Sinonasal Biofilms","volume":"59","author":"Chiu","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"B10","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1002\/alr.21892","article-title":"Tolerance and Pharmacokinetics of a Ciprofloxacin-Coated Sinus Stent in a Preclinical Model","volume":"7","author":"Cho","year":"2017","journal-title":"Int. Forum Allergy Rhinol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.iac.2019.12.009","article-title":"The Microbiome and Chronic Rhinosinusitis","volume":"40","author":"Cho","year":"2020","journal-title":"Immunol. Allergy Clin. North Am."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00540","article-title":"Sinus Microanatomy and Microbiota in a Rabbit Model of Rhinosinusitis","volume":"7","author":"Cho","year":"2018","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1002\/alr.22287","article-title":"Investigating the Correlation Between Mucus Cytokine Levels, Inflammatory Cell Counts, and Baseline Quality-of-Life Measures in Chronic Rhinosinusitis","volume":"9","author":"Chowdhury","year":"2019","journal-title":"Int. Forum Allergy Rhinol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1093\/nar\/gkt1244","article-title":"Ribosomal Database Project: Data and Tools for High Throughput rRNA Analysis","volume":"42","author":"Cole","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2460","DOI":"10.1093\/bioinformatics\/btq461","article-title":"Search and Clustering Orders of Magnitude Faster Than BLAST","volume":"26","author":"Edgar","year":"2010","journal-title":"Bioinformatics"},{"key":"B16","doi-asserted-by":"publisher","first-page":"074161","DOI":"10.1101\/074161","article-title":"SINTAX: A Simple non-Bayesian Taxonomy Classifier for 16s and ITS Sequences","author":"Edgar","year":"2016","journal-title":"bioRxiv"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1101\/081257","article-title":"UNOISE2: Improved Error-Correction for Illumina 16s and ITS Amplicon Sequencing","author":"Edgar","year":"2016","journal-title":"bioRxiv [Preprint]"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e1005846","DOI":"10.1371\/journal.ppat.1005846","article-title":"Evidence and Role for Bacterial Mucin Degradation in Cystic Fibrosis Airway Disease","volume":"12","author":"Flynn","year":"2016","journal-title":"PloS Pathog."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4193\/Rhin20.600","article-title":"European Position Paper on Rhinosinusitis and Nasal Polyps 2020","volume":"58","author":"Fokkens","year":"2020","journal-title":"Rhinology"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/101534","article-title":"Effects of Cryotherapy on the Maxillary Antrostomy Patency in a Rabbit Model of Chronic Rhinosinusitis","volume":"2013","author":"Gocea","year":"2013","journal-title":"BioMed. Res. Int."},{"key":"B21","doi-asserted-by":"publisher","first-page":"339","DOI":"10.2500\/ajr.2007.21.3032","article-title":"A Sheep Model for the Study of Biofilms in Rhinosinusitis","volume":"21","author":"Ha","year":"2007","journal-title":"Am. J. Rhinol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1038\/ismej.2011.41","article-title":"Transitions in Bacterial Communities Along the 2000 Km Salinity Gradient of the Baltic Sea","volume":"5","author":"Herlemann","year":"2011","journal-title":"ISME J."},{"key":"B23","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1002\/alr.21871","article-title":"Evidence of Microbiota Dysbiosis in Chronic Rhinosinusitis","volume":"7","author":"Hoggard","year":"2017","journal-title":"Int. Forum Allergy Rhinol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1001\/archotol.127.6.657","article-title":"Chronic Bacterial Rhinosinusitis: Description of a Mouse Model","volume":"127","author":"Jacob","year":"2001","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e115","DOI":"10.2500\/ajra.2014.28.4030","article-title":"A Simple Animal Model of Staphylococcus Aureus Biofilm in Sinusitis","volume":"28","author":"Jia","year":"2014","journal-title":"Am. J. Rhinol. Allergy"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2933","DOI":"10.2147\/IJN.S130160","article-title":"Efficacy of Silk Fibroin-Nano Silver Against Staphylococcus Aureus Biofilms in a Rabbit Model of Sinusitis","volume":"12","author":"Jia","year":"2017","journal-title":"Int. J. Nanomedicine"},{"key":"B27","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1111\/cea.12644","article-title":"Role of Ifn-\u03b3, IL-13, and IL-17 on Mucociliary Differentiation of Nasal Epithelial Cells in Chronic Rhinosinusitis With Nasal Polyps","volume":"46","author":"Jiao","year":"2016","journal-title":"Clin. Exp. Allergy"},{"key":"B28","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.alit.2014.12.006","article-title":"Immunopathology of Chronic Rhinosinusitis","volume":"64","author":"Kato","year":"2015","journal-title":"Allergol. Int."},{"key":"B29","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1053\/ajot.2000.9874","article-title":"Computed Tomography vs. Magnetic Resonance Imaging of Acute Bacterial Sinusitis: A Rabbit Model","volume":"21","author":"Kerschner","year":"2000","journal-title":"Am. J. Otolaryngol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.aller.2015.04.004","article-title":"Induction of Nasal Polyps Using House Dust Mite and Staphylococcal Enterotoxin B in C57BL\/6 Mice","volume":"44","author":"Khalmuratova","year":"2016","journal-title":"Allergol. Immunopathol. (Madr)"},{"key":"B31","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/s11908-011-0166-z","article-title":"Chronic Rhinosinusitis as a Multifactorial Inflammatory Disorder","volume":"13","author":"Lee","year":"2011","journal-title":"Curr. Infect. Dis. Rep."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1097\/MLG.0b013e3181671b74","article-title":"Developing a Rabbit Model of Rhinogenic Chronic Rhinosinusitis","volume":"118","author":"Liang","year":"2008","journal-title":"Laryngoscope"},{"key":"B33","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1002\/lio2.21","article-title":"Innate Immunity and Chronic Rhinosinusitis: What We Have Learned From Animal Models","volume":"1","author":"London","year":"2016","journal-title":"Laryngoscope Investig. Otolaryngol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"820","DOI":"10.3928\/0090-4481-19981201-09","article-title":"The Surgical Management of Chronic Sinusitis in Children","volume":"27","author":"Lusk","year":"1998","journal-title":"Pediatr. Ann."},{"key":"B35","doi-asserted-by":"publisher","first-page":"69","DOI":"10.4193\/rhinol\/19.015","article-title":"Animal Models for Inflammatory Mucosal Disease and Their Potential for Studying the Microbiome in Chronic Rhinosinusitis","volume":"2","author":"Lux","year":"2019","journal-title":"Rhinology Online"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1579","DOI":"10.1097\/00005537-199712000-00001","article-title":"Acute Sinusitis in the Rabbit: A New Rhinogenic Model","volume":"107","author":"Marks","year":"1997","journal-title":"Laryngoscope"},{"key":"B37","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1590\/s0102-86502014000500005","article-title":"An Experimental Model of Chronic Rhinosinusitis in Rabbits Without Bacterial Inoculation","volume":"29","author":"Migliavacca","year":"2014","journal-title":"Acta Cir. Bras."},{"key":"B38","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1007\/s12070-011-0120-2","article-title":"Comparison of Histopathological and CT Findings in Experimental Rabbit Sinusitis","volume":"63","author":"Ozcan","year":"2011","journal-title":"Indian J. Otolaryngol. Head Neck Surg."},{"key":"B39","doi-asserted-by":"publisher","first-page":"2037","DOI":"10.1111\/all.14276","article-title":"The International Sinonasal Microbiome Study: A Multicentre, Multinational Characterization of Sinonasal Bacterial Ecology","volume":"75","author":"Paramasivan","year":"2020","journal-title":"Allergy"},{"key":"B40","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1177\/0192623311409594","article-title":"Evaluation of the Rabbit Nasal Cavity in Inhalation Studies and a Comparison With Other Common Laboratory Species and Man","volume":"39","author":"Pereira","year":"2011","journal-title":"Toxicol. Pathol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"2095","DOI":"10.1097\/00005537-200012000-00023","article-title":"Bone Involvement in Sinusitis: An Apparent Pathway for the Spread of Disease","volume":"110","author":"Perloff","year":"2000","journal-title":"Laryngoscope"},{"key":"B42","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1002\/lio2.29","article-title":"Animal Models in CRS and Pathophysiologic Insights Gained: A Systematic Review","volume":"1","author":"Shin","year":"2016","journal-title":"Laryngoscope Investig. Otolaryngol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1513\/pats.201003-028RN","article-title":"Treatment Options for Chronic Rhinosinusitis","volume":"8","author":"Suh","year":"2011","journal-title":"AnnalsATS"},{"key":"B44","doi-asserted-by":"publisher","first-page":"597","DOI":"10.2500\/ajra.2009.23.3398","article-title":"In Vivo Effects of Citric Acid\/Zwitterionic Surfactant Cleansing Solution on Rabbit Sinus Mucosa","volume":"23","author":"Tamashiro","year":"2009","journal-title":"Am. J. Rhinol. Allergy"},{"key":"B45","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/j.jaci.2011.07.049","article-title":"Pathogenesis of Chronic Rhinosinusitis: Inflammation","volume":"128","author":"Van Crombruggen","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01481","article-title":"The Immunology of Wild Rodents: Current Status and Future Prospects","volume":"8","author":"Viney","year":"2017","journal-title":"Front. Immunol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.intimp.2017.10.032","article-title":"Broncho-Vaxom in Pediatric Recurrent Respiratory Tract Infections: A Systematic Review and Meta-Analysis","volume":"54","author":"Yin","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"32","DOI":"10.14639\/0392-100X-1143","article-title":"The Value of Nigella Sativa in the Treatment of Experimentally Induced Rhinosinusitis","volume":"37","author":"Yoruk","year":"2017","journal-title":"Acta Otorhinolaryngol. Ital"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.585625\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T05:55:10Z","timestamp":1631598910000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.585625\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,14]]},"references-count":48,"alternative-id":["10.3389\/fcimb.2021.585625"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2021.585625","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,14]]},"article-number":"585625"}}