Remodeling of Paranasal Sinuses Mucosa Functions in Response to Biofilm-Induced Inflammation

References

• Fokkens WJ, Lund VJ, Hopkins C, et al. European position paper on rhinosinusitis and nasal polyps 2020. Rhinology. 2020;58(Suppl S29):1.
   Google Scholar
• Fokkens WJ, Lund VJ, Hopkins C, et al. Executive summary of EPOS 2020 including integrated care pathways. Rhinology. 2020;58(2):82–111. doi:10.4193/Rhin20.601
   PubMedGoogle Scholar
• Bachert C, Zhang N, van Zele T, Gevaert P. Chronic rhinosinusitis: from one disease to different phenotypes. Pediatr Allergy Immunol. 2012;23(22):2–4. doi:10.1111/j.1399-3038.2012.01318.x
   Google Scholar
• Bachert C, Marple B, Schlosser RJ, et al. Adult chronic rhinosinusitis. Nature Reviews Disease Primers. 2020;6(1):86. doi:10.1038/s41572-020-00218-1
   PubMed Web of Science ®Google Scholar
• Rudmik L, Smith TL. Quality of life in patients with chronic rhinosinusitis. Curr Allergy Asthma Rep. 2011;11(3):247–252. doi:10.1007/s11882-010-0175-2
   PubMed Web of Science ®Google Scholar
• Dykewicz MS, Hamilos DL. Rhinitis and sinusitis. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S103–115. doi:10.1016/j.jaci.2009.12.989
   PubMed Web of Science ®Google Scholar
• La Mantia I, Ragusa M, Grigaliute E, et al. Sensibility, specificity, and accuracy of the Sinonasal Outcome Test 8 (SNOT-8) in patients with chronic rhinosinusitis (CRS): a cross-sectional cohort study. Europ Arch Oto Rhino Laryngol. 2023;280(7):3259–3264. doi:10.1007/s00405-023-07855-8
   Web of Science ®Google Scholar
• Cope EK, Goldberg AN, Pletcher SD, Lynch SV. Compositionally and functionally distinct sinus microbiota in chronic rhinosinusitis patients have immunological and clinically divergent consequences. Microbiome. 2017;5(1):53. doi:10.1186/s40168-017-0266-6
   PubMedGoogle Scholar
• Cho SH, Hamilos DL, Han DH, Laidlaw TM. Phenotypes of Chronic Rhinosinusitis. J Aller Clin Immunol Pract. 2020;8(5):1505–1511. doi:10.1016/j.jaip.2019.12.021
   PubMed Web of Science ®Google Scholar
• Akdis CA, Bachert C, Cingi C, et al. Endotypes and phenotypes of chronic rhinosinusitis: APRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology. J Aller Clin Immunol. 2013;131(6):1479–1490. doi:10.1016/j.jaci.2013.02.036
   PubMed Web of Science ®Google Scholar
• La Mantia I, Grigaliute E, Ragusa M, et al. Effectiveness and rapidity on olfactory function recovery in CRS patients treated with Dupilumab: a real life prospective controlled study. Europ Arch Oto Rhino Laryngol. 2023;2023:1.
   Google Scholar
• Kato A, Schleimer RP, Bleier BS. Mechanisms and pathogenesis of chronic rhinosinusitis. J Aller Clin Immunol. 2022;149(5):1491–1503. doi:10.1016/j.jaci.2022.02.016
   Web of Science ®Google Scholar
• Tomassen P, Vandeplas G, Van Zele T, et al. Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. J Allerg Clin Immunol. 2016;137(5):1449–1456.e1444. doi:10.1016/j.jaci.2015.12.1324
   PubMed Web of Science ®Google Scholar
• He Y, Fu Y, Wu Y, Zhu T, Li H. Pathogenesis and treatment of chronic rhinosinusitis from the perspective of sinonasal epithelial dysfunction. Front Med. 2023;2023:10.
   Google Scholar
• Stevens WW, Schleimer RP, Kern RC. chronic rhinosinusitis with nasal polyps. J Aller Clin Immunol Pract. 2016;4(4):565–572. doi:10.1016/j.jaip.2016.04.012
   PubMed Web of Science ®Google Scholar
• Schleimer RP. Immunopathogenesis of chronic rhinosinusitis and nasal polyposis. Annu Rev Pathol. 2017;12:331–357. doi:10.1146/annurev-pathol-052016-100401
   PubMed Web of Science ®Google Scholar
• Lam K, Schleimer R, Kern RC. the etiology and pathogenesis of chronic rhinosinusitis: a review of current hypotheses. Curr Aller Asthma Rep. 2015;15(7):41. doi:10.1007/s11882-015-0540-2
   PubMed Web of Science ®Google Scholar
• Cho DY, Hunter RC, Ramakrishnan VR. The Microbiome and chronic rhinosinusitis. Immunol Aller Clin North Am. 2020;40(2):251–263. doi:10.1016/j.iac.2019.12.009
   Web of Science ®Google Scholar
• Antonino M, Nicolò M, Jerome Renee L, et al. Single-nucleotide polymorphism in chronic rhinosinusitis: a systematic review. Clin Otolaryngol. 2022;47(1):14–23. doi:10.1111/coa.13870
   PubMed Web of Science ®Google Scholar
• Suzuki M, Suzuki T, Watanabe M, et al. Role of intracellular zinc in molecular and cellular function in allergic inflammatory diseases. Allergol Internat. 2021;70(2):190–200. doi:10.1016/j.alit.2020.09.007
   Web of Science ®Google Scholar
• Aggarwal N, Kitano S, Puah GRY, Kittelmann S, Hwang IY, Chang MW. Microbiome and human health: current understanding, engineering, and enabling technologies. Chem Rev. 2023;123(1):31–72. doi:10.1021/acs.chemrev.2c00431
   PubMed Web of Science ®Google Scholar
• Bassiouni A, Paramasivan S, Shiffer A, et al. Microbiotyping the sinonasal microbiome. Frontiers in Cellular and Infection Microbiology. 2020;10:137. doi:10.3389/fcimb.2020.00137
   Web of Science ®Google Scholar
• Paramasivan S, Bassiouni A, Shiffer A, et al. The international sinonasal microbiome study: a multicentre, multinational characterization of sinonasal bacterial ecology. Allergy. 2020;75(8):2037–2049. doi:10.1111/all.14276
   PubMed Web of Science ®Google Scholar
• Abreu NA, Nagalingam NA, Song Y, et al. Sinus microbiome diversity depletion and Corynebacterium tuberculostearicum enrichment mediates rhinosinusitis. Sci Transl Med. 2012;4(151):151ra124. doi:10.1126/scitranslmed.3003783
   PubMed Web of Science ®Google Scholar
• Biswas K, Hoggard M, Jain R, Taylor MW, Douglas RG. The nasal microbiota in health and disease: variation within and between subjects. Front Microbiol. 2015;9:134. doi:10.3389/fmicb.2015.00134
   PubMed Web of Science ®Google Scholar
• Radaic A, Kapila YL. The oralome and its dysbiosis: new insights into oral microbiome-host interactions. Computat Struct Biotechnol J. 2021;19:1335–1360. doi:10.1016/j.csbj.2021.02.010
   PubMed Web of Science ®Google Scholar
• Tokajuk J, Deptuła P, Piktel E, et al. Cathelicidin LL-37 in health and diseases of the oral cavity. Biomedicines. 2022;10(5):1086. doi:10.3390/biomedicines10051086
   Web of Science ®Google Scholar
• Canovas J, Baldry M, Bojer MS, et al. Cross-talk between staphylococcus aureus and other staphylococcal species via the agr quorum sensing system. Front Microbiol. 2016;7:1733. doi:10.3389/fmicb.2016.01733
   PubMed Web of Science ®Google Scholar
• Coquant G, Aguanno D, Pham S, et al. Gossip in the gut: quorum sensing, a new player in the host-microbiota interactions. World J Gastroenterol. 2021;27(42):7247–7270. doi:10.3748/wjg.v27.i42.7247
   Web of Science ®Google Scholar
• Li K, Ly K, Mehta S, Braithwaite A. Importance of crosstalk between the microbiota and the neuroimmune system for tissue homeostasis. Clin Translat Immunol. 2022;11(5):e1394. doi:10.1002/cti2.1394
   Web of Science ®Google Scholar
• Wagner mackenzie B, Waite DW, Hoggard M, Douglas RG, Taylor MW, Biswas K. Bacterial community collapse: a meta-analysis of the sinonasal microbiota in chronic rhinosinusitis. Environm Microbiol. 2017;19(1):381–392. doi:10.1111/1462-2920.13632
   Google Scholar
• Joss TV, Burke CM, Hudson BJ, et al. Bacterial communities vary between sinuses in chronic rhinosinusitis patients. Front Microbiol. 2016:6. doi:10.3389/fmicb.2016.00006
   Google Scholar
• Barshak MB, Durand ML. The role of infection and antibiotics in chronic rhinosinusitis. Laryngos Investigat Otolaryngol. 2017;2(1):36–42. doi:10.1002/lio2.61
   Google Scholar
• Chmiel JF, Konstan MW, Elborn JS. Antibiotic and anti-inflammatory therapies for cystic fibrosis. Cold Spring Harbor Perspect Med. 2013;3(10):a009779. doi:10.1101/cshperspect.a009779
   PubMed Web of Science ®Google Scholar
• Jamal M, Ahmad W, Andleeb S, et al. Bacterial biofilm and associated infections. J Chin Med Assoc. 2018;81(1):7–11. doi:10.1016/j.jcma.2017.07.012
   PubMed Web of Science ®Google Scholar
• Penesyan A, Paulsen IT, Kjelleberg S, Gillings MR. Three faces of biofilms: a microbial lifestyle, a nascent multicellular organism, and an incubator for diversity. NPJ Biof Microb. 2021;7(1):80. doi:10.1038/s41522-021-00251-2
   Web of Science ®Google Scholar
• Huang Y, Qin F, Li S, et al. The mechanisms of biofilm antibiotic resistance in chronic rhinosinusitis: a review. Med. 2022;101(49):e32168. doi:10.1097/MD.0000000000032168
   Web of Science ®Google Scholar
• Łusiak-szelachowska M, Weber-Dąbrowska B, Żaczek M, Górski A. Anti-biofilm activity of bacteriophages and lysins in chronic rhinosinusitis. Acta Virol. 2021;65(2):127–140. doi:10.4149/av_2021_203
   Web of Science ®Google Scholar
• Sabino HAC, Valera FCP, Santos DV, et al. Biofilm and planktonic antibiotic resistance in patients with acute exacerbation of chronic rhinosinusitis. Front Cell Infect Microbiol. 2021;11:813076. doi:10.3389/fcimb.2021.813076
   Web of Science ®Google Scholar
• Hoggard M, Biswas K, Zoing M, Wagner Mackenzie B, Taylor MW, Douglas RG. Evidence of microbiota dysbiosis in chronic rhinosinusitis. Internat Forum Aller Rhinol. 2017;7(3):230–239. doi:10.1002/alr.21871
   Web of Science ®Google Scholar
• Hochstim CJ, Masood R, Rice DH. Biofilm and persistent inflammation in endoscopic sinus surgery. Otolaryngol Head Neck Surg. 2010;143(5):697–698. doi:10.1016/j.otohns.2010.07.017
   Web of Science ®Google Scholar
• Foreman A, Wormald PJ. Different biofilms, different disease? A clinical outcomes study. Laryngoscope. 2010;120(8):1701–1706. doi:10.1002/lary.21024
   PubMed Web of Science ®Google Scholar
• Martinez-Paredes JF, Choby G, Marino M, et al. Endoscopic outcomes in patients with AERD treated with topical antibiotics and intranasal corticosteroids. Front Cell Infect Microbiol. 2022;12:812215. doi:10.3389/fcimb.2022.812215
   Web of Science ®Google Scholar
• Deal RT, Kountakis SE. Significance of nasal polyps in chronic rhinosinusitis: symptoms and surgical outcomes. Laryngoscope. 2004;114(11):1932–1935. doi:10.1097/01.mlg.0000147922.12228.1f
   PubMed Web of Science ®Google Scholar
• Psaltis AJ, Weitzel EK, Ha KR, Wormald PJ. The effect of bacterial biofilms on post-sinus surgical outcomes. Am J Rhinol. 2008;22(1):1–6. doi:10.2500/ajr.2008.22.3119
   PubMedGoogle Scholar
• Singhal D, Foreman A, Jervis-Bardy J, Wormald PJ. Staphylococcus aureus biofilms: nemesis of endoscopic sinus surgery. Laryngoscope. 2011;121(7):1578–1583. doi:10.1002/lary.21805
   PubMed Web of Science ®Google Scholar
• Salzano FA, Marino L, Salzano G, et al. Microbiota composition and the integration of exogenous and endogenous signals in reactive nasal inflammation. J Immunol Res. 2018;2018:2724951. doi:10.1155/2018/2724951
   PubMed Web of Science ®Google Scholar
• Kim DY, Cho SH, Takabayashi T, Schleimer RP. Chronic rhinosinusitis and the coagulation system. Allergy Asthma Immunol Res. 2015;7(5):421–430. doi:10.4168/aair.2015.7.5.421
   PubMed Web of Science ®Google Scholar
• De Boeck I, Wittouck S, Martens K, et al. Anterior nares diversity and pathobionts represent sinus microbiome in chronic rhinosinusitis. mSphere. 2019;4(6). doi:10.1128/mSphere.00532-19
   Web of Science ®Google Scholar
• Man WH, de Steenhuijsen Piters WAA, Bogaert D. The microbiota of the respiratory tract: gatekeeper to respiratory health. Nature Reviews Microbiology. 2017;15(5):259–270. doi:10.1038/nrmicro.2017.14
   PubMed Web of Science ®Google Scholar
• Dowd SE, Wolcott RD, Sun Y, McKeehan T, Smith E, Rhoads D. Polymicrobial nature of chronic diabetic foot ulcer biofilm infections determined using bacterial tag encoded FLX amplicon pyrosequencing (bTEFAP). PLoS One. 2008;3(10):e3326. doi:10.1371/journal.pone.0003326
   PubMed Web of Science ®Google Scholar
• Sugimoto S, Iwamoto T, Takada K, et al. Staphylococcus epidermidis Esp degrades specific proteins associated with Staphylococcus aureus biofilm formation and host-pathogen interaction. Journal of Bacteriology. 2013;195(8):1645–1655. doi:10.1128/JB.01672-12
   Web of Science ®Google Scholar
• Zipperer A, Konnerth MC, Laux C, et al. Human commensals producing a novel antibiotic impair pathogen colonization. Nature. 2016;535(7613):511–516. doi:10.1038/nature18634
   PubMed Web of Science ®Google Scholar
• Yan M, Pamp SJ, Fukuyama J, et al. Nasal microenvironments and interspecific interactions influence nasal microbiota complexity and S. aureus carriage. Cell Host Microbe. 2013;14(6):631–640. doi:10.1016/j.chom.2013.11.005
   PubMed Web of Science ®Google Scholar
• Menberu MA, Liu S, Cooksley C, et al. Corynebacterium accolens has antimicrobial activity against staphylococcus aureus and methicillin-resistant S. aureus pathogens isolated from the sinonasal niche of chronic rhinosinusitis patients. Pathogens (Basel, Switzerland). 2021;10(2). doi:10.3390/pathogens10020207
   Web of Science ®Google Scholar
• Huang S, Hon K, Bennett C, et al. Corynebacterium accolens inhibits Staphylococcus aureus induced mucosal barrier disruption. Frontiers in Microbiology. 2022;2022:13.
   Google Scholar
• Menberu MA, Hayes AJ, Liu S, Psaltis AJ, Wormald PJ, Vreugde S. Tween 80 and its derivative oleic acid promote the growth of Corynebacterium accolens and inhibit Staphylococcus aureus clinical isolates. Internat Foru Aller Rhinol. 2021;11(4):810–813. doi:10.1002/alr.22730
   Web of Science ®Google Scholar
• De Boeck I, Wittouck S, Martens K, et al. The nasal mutualist Dolosigranulum pigrum AMBR11 supports homeostasis via multiple mechanisms. iScience. 2021;24(9):102978. doi:10.1016/j.isci.2021.102978
   Web of Science ®Google Scholar
• Dunne EM, Murad C, Sudigdoadi S, et al. Carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus in Indonesian children: a cross-sectional study. PLoS One. 2018;13(4):e0195098. doi:10.1371/journal.pone.0195098
   Web of Science ®Google Scholar
• Pettigrew MM, Gent JF, Revai K, Patel JA, Chonmaitree T. Microbial interactions during upper respiratory tract infections. Emerging Infectious Diseases. 2008;14(10):1584–1591. doi:10.3201/eid1410.080119
   PubMed Web of Science ®Google Scholar
• Regev-Yochay G, Dagan R, Raz M, et al. Association between carriage of streptococcus pneumoniae and staphylococcus aureus in children. JAMA. 2004;292(6):716–720. doi:10.1001/jama.292.6.716
   PubMed Web of Science ®Google Scholar
• Dunne EM, Smith-Vaughan HC, Robins-Browne RM, Mulholland EK, Satzke C. Nasopharyngeal microbial interactions in the era of pneumococcal conjugate vaccination. Vaccine. 2013;31(19):2333–2342. doi:10.1016/j.vaccine.2013.03.024
   PubMed Web of Science ®Google Scholar
• Aurora R, Chatterjee D, Hentzleman J, Prasad G, Sindwani R, Sanford T. Contrasting the microbiomes from healthy volunteers and patients with chronic rhinosinusitis. JAMA Otolaryngology-- Head & Neck Surgery. 2013;139(12):1328–1338. doi:10.1001/jamaoto.2013.5465
   PubMed Web of Science ®Google Scholar
• Huntley KS, Raber J, Fine L, Bernstein JA. Influence of the microbiome on chronic rhinosinusitis with and without polyps: an evolving discussion. Frontiers in Allergy. 2021;2:737086. doi:10.3389/falgy.2021.737086
   PubMedGoogle Scholar
• Diaz PI, Valm AM. Microbial interactions in oral communities mediate emergent biofilm properties. J Dent Res. 2020;99(1):18–25. doi:10.1177/0022034519880157
   PubMed Web of Science ®Google Scholar
• Morillo-Lopez V, Sjaarda A, Islam I, Borisy GG, Mark Welch JL. Corncob structures in dental plaque reveal microhabitat taxon specificity. Microbiome. 2022;10(1):145. doi:10.1186/s40168-022-01323-x
   PubMed Web of Science ®Google Scholar
• Suzuki M, Ramezanpour M, Cooksley C, et al. Zinc-depletion associates with tissue eosinophilia and collagen depletion in chronic rhinosinusitis. Rhinology. 2020;58(5):451–459. doi:10.4193/Rhin19.383
   Web of Science ®Google Scholar
• Islam T, Albracht-Schulte K, Ramalingam L, et al. Anti-inflammatory mechanisms of polyphenols in adipose tissue: role of gut microbiota, intestinal barrier integrity and zinc homeostasis. The Journal of Nutritional Biochemistry. 2023;115:109242. doi:10.1016/j.jnutbio.2022.109242
   Web of Science ®Google Scholar
• Yu M, Lee -W-W, Tomar D, et al. Regulation of T cell receptor signaling by activation-induced zinc influx. Journal of Experimental Medicine. 2011;208(4):775–785. doi:10.1084/jem.20100031
   PubMed Web of Science ®Google Scholar
• Cerasi M, Ammendola S, Battistoni A. Competition for zinc binding in the host-pathogen interaction. Frontiers in Cellular and Infection Microbiology. 2013;3:3. doi:10.3389/fcimb.2013.00003
   Web of Science ®Google Scholar
• Wan Y, Zhang B. The impact of zinc and zinc homeostasis on the intestinal mucosal barrier and intestinal diseases. Biomolecules. 2022;12(7):900. doi:10.3390/biom12070900
   Web of Science ®Google Scholar
• Yunker R, Han GG, Luong H, Vaishnava S. Intestinal epithelial cell intrinsic zinc homeostasis is critical for host-microbiome symbiosis. J Immunol. 2023;210(1_Supplement):18–82. doi:10.4049/jimmunol.210.Supp.82.18
   Web of Science ®Google Scholar
• Lopez CA, Skaar EP. The impact of dietary transition metals on host-bacterial interactions. Cell Host Microbe. 2018;23(6):737–748. doi:10.1016/j.chom.2018.05.008
   PubMed Web of Science ®Google Scholar
• Gielda LM, DiRita VJ. Zinc competition among the intestinal microbiota. MBio. 2012;3(4). doi:10.1128/mBio.00171-12
   Web of Science ®Google Scholar
• Djoko KY. Control of nutrient metal availability during host-microbe interactions: beyond nutritional immunity. J Biol Inorg Chem. 2023;28(5):451–456. doi:10.1007/s00775-023-02007-z
   Google Scholar
• Liu JZ, Jellbauer S, Poe AJ, et al. Zinc sequestration by the neutrophil protein calprotectin enhances Salmonella growth in the inflamed gut. Cell Host Microbe. 2012;11(3):227–239. doi:10.1016/j.chom.2012.01.017
   PubMed Web of Science ®Google Scholar
• Xia P, Lian S, Wu Y, Yan L, Quan G, Zhu G. Zinc is an important inter-kingdom signal between the host and microbe. Veterin Res. 2021;52(1):39. doi:10.1186/s13567-021-00913-1
   Google Scholar
• Amirapu S, Biswas K, Radcliff FJ, Wagner Mackenzie B, Ball S, Douglas RG. Sinonasal tissue remodelling during chronic rhinosinusitis. Int J Otolaryngol. 2021;2021:7428955. doi:10.1155/2021/7428955
   PubMedGoogle Scholar
• Xiang R, Zhang QP, Zhang W, et al. Different effects of allergic rhinitis on nasal mucosa remodeling in chronic rhinosinusitis with and without nasal polyps. Eur Arch Otorhinolaryngol. 2019;276(1):115–130. doi:10.1007/s00405-018-5195-x
   PubMed Web of Science ®Google Scholar
• Lee HY, Pyo JS, Kim SJ. Distinct patterns of tissue remodeling and their prognostic role in chronic rhinosinusitis. ORL J Otorhinolaryngol Relat Spec. 2021;83(6):457–463. doi:10.1159/000515005
   PubMed Web of Science ®Google Scholar
• Kuhar HN, Tajudeen BA, Mahdavinia M, Gattuso P, Ghai R, Batra PS. Inflammatory infiltrate and mucosal remodeling in chronic rhinosinusitis with and without polyps: structured histopathologic analysis. Int Forum Allergy Rhinol. 2017;7(7):679–689. doi:10.1002/alr.21943
   Web of Science ®Google Scholar
• Do TQ, Barham HP, Earls P, et al. Clinical implications of mucosal remodeling from chronic rhinosinusitis. Int Forum Allergy Rhinol. 2016;6(8):835–840. doi:10.1002/alr.21754
   Web of Science ®Google Scholar
• Meng J, Zhou P, Liu Y, et al. The development of nasal polyp disease involves early nasal mucosal inflammation and remodelling. PLoS One. 2013;8(12):e82373. doi:10.1371/journal.pone.0082373
   PubMed Web of Science ®Google Scholar
• Radajewski K, Kalińczak-Górna P, Zdrenka M, et al. Short term pre-operative oral corticosteroids-tissue remodeling in chronic rhinosinusitis with nasal polyps. J Clin Med. 2021;10(15). doi:10.3390/jcm10153346
   Web of Science ®Google Scholar
• Watelet JB, Eloy PH, van Cauwenberge PB. Drug management in chronic rhinosinusitis: identification of the needs. Ther Clin Risk Manag. 2007;3(1):47–57. doi:10.2147/tcrm.2007.3.1.47
   PubMedGoogle Scholar
• Lee K, Tai J, Lee SH, Kim TH. Advances in the knowledge of the underlying airway remodeling mechanisms in chronic rhinosinusitis based on the endotypes: a review. Int J Mol Sci. 2021;22:2.
   Web of Science ®Google Scholar
• Ryu G, Mo JH, Shin HW. Epithelial-to-mesenchymal transition in neutrophilic chronic rhinosinusitis. Curr Opin Allergy Clin Immunol. 2021;21(1):30–37. doi:10.1097/ACI.0000000000000701
   PubMed Web of Science ®Google Scholar
• Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2014;15(3):178–196. doi:10.1038/nrm3758
   PubMed Web of Science ®Google Scholar
• Yan B, Wang Y, Li Y, Wang C, Zhang L. Inhibition of arachidonate 15-lipoxygenase reduces the epithelial-mesenchymal transition in eosinophilic chronic rhinosinusitis with nasal polyps. Int Forum Allergy Rhinol. 2019;9(3):270–280. doi:10.1002/alr.22243
   PubMed Web of Science ®Google Scholar
• Zhong B, Seah JJ, Liu F, Ba L, Du J, Wang Y. The role of hypoxia in the pathophysiology of chronic rhinosinusitis. Allergy. 2022;77(11):3217–3232. doi:10.1111/all.15384
   PubMed Web of Science ®Google Scholar
• Cheng J, Chen J, Zhao Y, Yang J, Xue K, Wang Z. MicroRNA-761 suppresses remodeling of nasal mucosa and epithelial-mesenchymal transition in mice with chronic rhinosinusitis through LCN2. Stem Cell Res Ther. 2020;11(1):151. doi:10.1186/s13287-020-01598-7
   Web of Science ®Google Scholar
• Xia Y, Wang H, Yin J. The role of epithelial-mesenchymal transition in chronic rhinosinusitis. Internat Arch Aller Immunol. 2022;183(10):1029–1039. doi:10.1159/000524950
   Web of Science ®Google Scholar
• Ye Y, Zhao J, Ye J, et al. The role of autophagy in the overexpression of MUC5AC in patients with chronic rhinosinusitis. Internat Immunopharmacol. 2019;71:169–180. doi:10.1016/j.intimp.2019.03.028
   PubMed Web of Science ®Google Scholar
• Hoggard M, Wagner Mackenzie B, Jain R, Taylor MW, Biswas K, Douglas RG. Chronic rhinosinusitis and the evolving understanding of microbial ecology in chronic inflammatory mucosal disease. Clin Microbiol Rev. 2017;30(1):321–348.
   PubMed Web of Science ®Google Scholar
• Tong J, Gu Q. Expression and clinical significance of mucin gene in chronic rhinosinusitis. Curr All Asthma Rep. 2020;20(11):63. doi:10.1007/s11882-020-00958-w
   Web of Science ®Google Scholar
• Suzuki M, Ramezanpour M, Cooksley C, et al. Metallothionein-3 is a clinical biomarker for tissue zinc levels in nasal mucosa. Auris Nasus Larynx. 2021;48(5):890–897. doi:10.1016/j.anl.2021.01.019
   Web of Science ®Google Scholar
• Hooshangi S, Bentley WE. From unicellular properties to multicellular behavior: bacteria quorum sensing circuitry and applications. Curr Opin Biotechnol. 2008;19(6):550–555. doi:10.1016/j.copbio.2008.10.007
   Web of Science ®Google Scholar
• Hibbing ME, Fuqua C, Parsek MR, Peterson SB. Bacterial competition: surviving and thriving in the microbial jungle. Nature Reviews Microbiology. 2010;8(1):15–25. doi:10.1038/nrmicro2259
   PubMed Web of Science ®Google Scholar
• Harrison F, Paul J, Massey RC, Buckling A. Interspecific competition and siderophore-mediated cooperation in Pseudomonas aeruginosa. ISME J. 2008;2(1):49–55. doi:10.1038/ismej.2007.96
   PubMed Web of Science ®Google Scholar
• Desai SK, Kenney LJ. Switching lifestyles is an in vivo adaptive strategy of bacterial pathogens. FrontCellular Infec Microb. 2019;9. doi:10.3389/fcimb.2019.00421
   Google Scholar
• Yarwood JM, Schlievert PM. Quorum sensing in Staphylococcus infections. J Clin Invest. 2003;112(11):1620–1625. doi:10.1172/JCI200320442
   PubMed Web of Science ®Google Scholar
• George EA, Muir TW. Molecular mechanisms of agr quorum sensing in virulent staphylococci. Chembiochem. 2007;8(8):847–855. doi:10.1002/cbic.200700023
   PubMed Web of Science ®Google Scholar
• Ramsey MM, Freire MO, Gabrilska RA, Rumbaugh KP, Lemon KP. Staphylococcus aureus shifts toward commensalism in response to Corynebacterium species. Front Microbiol. 2016;7:1230. doi:10.3389/fmicb.2016.01230
   PubMed Web of Science ®Google Scholar
• Mahdally NH, George RF, Kashef MT, Al-Ghobashy M, Murad FE, Attia AS. Staquorsin: a novel staphylococcus aureus agr-mediated quorum sensing inhibitor impairing virulence in vivo without notable resistance development. Front Microbiol. 2021;12:700494. doi:10.3389/fmicb.2021.700494
   PubMed Web of Science ®Google Scholar
• D’Argenio DA, Wu M, Hoffman LR, et al. Growth phenotypes of Pseudomonas aeruginosa lasR mutants adapted to the airways of cystic fibrosis patients. Mol Microbiol. 2007;64(2):512–533. doi:10.1111/j.1365-2958.2007.05678.x
   PubMed Web of Science ®Google Scholar
• Mateu-Borrás M, González-Alsina A, Doménech-Sánchez A, et al. Pseudomonas aeruginosa adaptation in cystic fibrosis patients increases C5a levels and promotes neutrophil recruitment. Virulence. 2022;13(1):215–224. doi:10.1080/21505594.2022.2028484
   PubMed Web of Science ®Google Scholar
• Hennemann LC, LaFayette SL, Malet JK, et al. LasR-deficient Pseudomonas aeruginosa variants increase airway epithelial mICAM-1 expression and enhance neutrophilic lung inflammation. PLoS Pathog. 2021;17(3):e1009375. doi:10.1371/journal.ppat.1009375
   PubMed Web of Science ®Google Scholar
• Cho DY, Skinner D, Hunter RC, et al. Contribution of Short Chain Fatty Acids to the Growth of Pseudomonas aeruginosa in Rhinosinusitis. Front Cell Infect Microbiol. 2020;10:412. doi:10.3389/fcimb.2020.00412
   Web of Science ®Google Scholar
• Flynn JM, Niccum D, Dunitz JM, Hunter RC. Evidence and Role for Bacterial Mucin Degradation in Cystic Fibrosis Airway Disease. PLoS Pathog. 2016;12(8):e1005846. doi:10.1371/journal.ppat.1005846
   Web of Science ®Google Scholar
• Tikhomirova A, Trappetti C, Paton JC, Kidd SP. The outcome of H. influenzae and S. pneumoniae inter-species interactions depends on pH, nutrient availability and growth phase. Int J Med Microbiol. 2015;305(8):881–892. doi:10.1016/j.ijmm.2015.09.003
   PubMed Web of Science ®Google Scholar
• Xavier JB, Foster KR. Cooperation and conflict in microbial biofilms. Proc Natl Acad Sci U S A. 2007;104(3):876–881. doi:10.1073/pnas.0607651104
   PubMed Web of Science ®Google Scholar
• Shin S-H, M-K Y, Park J, Geum S-Y. Immunopathologic Role of Eosinophils in Eosinophilic Chronic Rhinosinusitis. Int J Mol Sci. 2022;23(21):13313. doi:10.3390/ijms232113313
   Web of Science ®Google Scholar
• Gao N, Rezaee F. Airway Epithelial Cell Junctions as Targets for Pathogens and Antimicrobial Therapy. Pharmaceutics. 2022;14(12):2619. doi:10.3390/pharmaceutics14122619
   PubMed Web of Science ®Google Scholar
• Nomura K, Obata K, Keira T, et al. Pseudomonas aeruginosa elastase causes transient disruption of tight junctions and downregulation of PAR-2 in human nasal epithelial cells. Respir Res. 2014;15(1):21. doi:10.1186/1465-9921-15-21
   Google Scholar
• Kim Y, Lee Y, Heo G, et al. Modulation of intestinal epithelial permeability via protease-activated receptor-2-induced autophagy. Cells. 2022;11:5.
   Web of Science ®Google Scholar
• Horrocks V, King OG, Yip AYG, Marques IM, McDonald JAK. Role of the gut microbiota in nutrient competition and protection against intestinal pathogen colonization. Microbiology. 2023;169(8). doi:10.1099/mic.0.001377
   Google Scholar
• Giromini C, Baldi A, Rebucci R, et al. Role of short chain fatty acids to counteract inflammatory stress and mucus production in human intestinal HT29-MTX-E12 cells. Foods. 2022;11(13):1983. doi:10.3390/foods11131983
   Web of Science ®Google Scholar
• Pan M, Barua N, Ip M. Mucin-degrading gut commensals isolated from healthy faecal donor suppress intestinal epithelial inflammation and regulate tight junction barrier function. Front Immunol. 2022;2022;13.
   Google Scholar
• Hong H, Liao S, Chen F, Yang Q, Wang DY. Role of IL-25, IL-33, and TSLP in triggering united airway diseases toward type 2 inflammation. Allergy. 2020;75(11):2794–2804. doi:10.1111/all.14526
   PubMed Web of Science ®Google Scholar
• Kouakou YI, Lee RJ. Interkingdom detection of bacterial quorum-sensing molecules by mammalian taste receptors. Microorganisms. 2023;11(5):1295. doi:10.3390/microorganisms11051295
   Web of Science ®Google Scholar
• Martens K, Steelant B, Bullens DMA. Taste receptors: the gatekeepers of the airway epithelium. Cells. 2021;10(11):2889. doi:10.3390/cells10112889
   Web of Science ®Google Scholar
• Eum SY, Jaraki D, Bertrand L, András IE, Toborek M. Disruption of epithelial barrier by quorum-sensing N-3-(oxododecanoyl)-homoserine lactone is mediated by matrix metalloproteinases. Am J Physiol Gastrointest Liver Physiol. 2014;306(11):G992–g1001. doi:10.1152/ajpgi.00016.2014
   PubMed Web of Science ®Google Scholar
• Nagi M, Chapple ILC, Sharma P, Kuehne SA, Hirschfeld J. Quorum sensing in oral biofilms: influence on host cells. Preprints. 2023;11(7):1688.
   Google Scholar
• Prevete N, Salzano FA, Rossi FW, et al. Role(s) of formyl-peptide receptors expressed in nasal epithelial cells. J Biol Regul Homeost Agents. 2011;25(4):553–564.
   Web of Science ®Google Scholar
• Altonsy MO, Kurwa HA, Lauzon GJ, et al. Corynebacterium tuberculostearicum, a human skin colonizer, induces the canonical nuclear factor-κB inflammatory signaling pathway in human skin cells. Immun Inflamm Dis. 2020;8(1):62–79. doi:10.1002/iid3.284
   Web of Science ®Google Scholar
• Rha MS, Kim SW, Chang DY, et al. Superantigen-related T(H)2 CD4(+) T cells in nonasthmatic chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol. 2020;145(5):1378–1388.e1310. doi:10.1016/j.jaci.2019.12.915
   Web of Science ®Google Scholar
• Xu SX, McCormick JK. Staphylococcal superantigens in colonization and disease. Front Cell Infect Microbiol. 2012;2:52. doi:10.3389/fcimb.2012.00052
   PubMed Web of Science ®Google Scholar
• John E, Laskow TC, Buchser WJ, et al. Zinc in innate and adaptive tumor immunity. J Transl Med. 2010;8(1):118. doi:10.1186/1479-5876-8-118
   PubMedGoogle Scholar
• Fernández MM, Guan R, Swaminathan CP, Malchiodi EL, Mariuzza RA. Crystal structure of staphylococcal enterotoxin I (SEI) in complex with a human major histocompatibility complex class II molecule. J Biol Chem. 2006;281(35):25356–25364. doi:10.1074/jbc.M603969200
   Web of Science ®Google Scholar
• Pless DD, Ruthel G, Reinke EK, Ulrich RG, Bavari S. Persistence of zinc-binding bacterial superantigens at the surface of antigen-presenting cells contributes to the extreme potency of these superantigens as T-cell activators. Infect Immun. 2005;73(9):5358–5366. doi:10.1128/IAI.73.9.5358-5366.2005
   Web of Science ®Google Scholar
• Fraser JD, Urban RG, Strominger JL, Robinson H. Zinc regulates the function of two superantigens. Proc Natl Acad Sci U S A. 1992;89(12):5507–5511. doi:10.1073/pnas.89.12.5507
   Web of Science ®Google Scholar
• Suzuki M, Cooksley C, Suzuki T, et al. TLR signals in epithelial cells in the nasal cavity and paranasal sinuses. Front Allergy. 2021;2021:2.
   Google Scholar
• Martens K, Seys SF, Alpizar YA, et al. Staphylococcus aureus enterotoxin B disrupts nasal epithelial barrier integrity. Clin Exp Allergy. 2021;51(1):87–98. doi:10.1111/cea.13760
   PubMed Web of Science ®Google Scholar
• Suvanprakorn P, Tongyen T, Prakhongcheep O, Laoratthaphong P, Chanvorachote P. Establishment of an anti-acne vulgaris evaluation method based on TLR2 and TLR4-mediated interleukin-8 production. Vivo. 2019;33(6):1929–1934.
   Web of Science ®Google Scholar
• Chegini Z, Didehdar M, Khoshbayan A, Karami J, Yousefimashouf M, Shariati A. The role of Staphylococcus aureus enterotoxin B in chronic rhinosinusitis with nasal polyposis. Cell Commun. 2022;20(1):29. doi:10.1186/s12964-022-00839-x
   Google Scholar
• Wang X, Zhao C, Ji W, Xu Y, Guo H. Relationship of TLR2, TLR4 and tissue remodeling in chronic rhinosinusitis. Int J Clin Exp Pathol. 2015;8(2):1199–1212.
   Web of Science ®Google Scholar
• Conley DB, Tripathi A, Seiberling KA, et al. Superantigens and chronic rhinosinusitis: skewing of T-cell receptor V beta-distributions in polyp-derived CD4+ and CD8+ T cells. Am J Rhinol. 2006;20(5):534–539. doi:10.2500/ajr.2006.20.2941
   Google Scholar
• Van Bruaene N, Bachert C. Tissue remodeling in chronic rhinosinusitis. Curr Opin Allergy Clin Immunol. 2011;11(1):8–11. doi:10.1097/ACI.0b013e32834233ef
   Web of Science ®Google Scholar
• Bassiouni A, Chen PG, Wormald PJ. Mucosal remodeling and reversibility in chronic rhinosinusitis. Curr Opin Allergy Clin Immunol. 2013;13(1):4–12. doi:10.1097/ACI.0b013e32835ad09e
   Web of Science ®Google Scholar
• Sanclement JA, Webster P, Thomas J, Ramadan HH. Bacterial biofilms in surgical specimens of patients with chronic rhinosinusitis. Laryngoscope. 2005;115(4):578–582. doi:10.1097/01.mlg.0000161346.30752.18
   PubMed Web of Science ®Google Scholar
• Hsu J, Peters AT. Pathophysiology of chronic rhinosinusitis with nasal polyp. Am J Rhinol Allergy. 2011;25(5):285–290. doi:10.2500/ajra.2011.25.3680
   Web of Science ®Google Scholar
• Bachert C, Zhang N, Patou J, van Zele T, Gevaert P. Role of staphylococcal superantigens in upper airway disease. Curr Opin Allergy Clin Immunol. 2008;8(1):34–38. doi:10.1097/ACI.0b013e3282f4178f
   PubMed Web of Science ®Google Scholar
• Ou J, Wang J, Xu Y, et al. Staphylococcus aureus superantigens are associated with chronic rhinosinusitis with nasal polyps: a meta-analysis. Eur Arch Otorhinolaryngol. 2014;271(10):2729–2736. doi:10.1007/s00405-014-2955-0
   Web of Science ®Google Scholar
• Ferreira-Duarte AP, Pinheiro-Torres AS, Takeshita WM, et al. Airway exposure to Staphylococcal enterotoxin type B (SEB) enhances the number and activity of bone marrow neutrophils via the release of multiple cytokines. Int Immunopharmacol. 2020;78:106009. doi:10.1016/j.intimp.2019.106009
   Web of Science ®Google Scholar
• Holm L. Dali server: structural unification of protein families. Nucleic Acids Res. 2022;50(W1):W210–W215. doi:10.1093/nar/gkac387
   PubMed Web of Science ®Google Scholar
• Greene CJ, Hu JC, Vance DJ, et al. Enhancement of humoral immunity by the type II heat-labile enterotoxin LT-IIb is dependent upon IL-6 and neutrophils. J Leukoc Biol. 2016;100(2):361–369. doi:10.1189/jlb.3A0415-153RR
   PubMed Web of Science ®Google Scholar
• Hajishengallis G, Tapping RI, Martin MH, et al. Toll-like receptor 2 mediates cellular activation by the B subunits of type II heat-labile enterotoxins. Infect Immun. 2005;73(3):1343–1349. doi:10.1128/IAI.73.3.1343-1349.2005
   PubMed Web of Science ®Google Scholar
• Odumosu O, Nicholas D, Yano H, Langridge W. AB Toxins: a Paradigm Switch from Deadly to Desirable. Toxins. 2010;2(7):1612–1645. doi:10.3390/toxins2071612
   PubMed Web of Science ®Google Scholar
• Yokoyama R, Itoh S, Kamoshida G, et al. Staphylococcal superantigen-like protein 3 binds to the Toll-like receptor 2 extracellular domain and inhibits cytokine production induced by Staphylococcus aureus, cell wall component, or lipopeptides in murine macrophages. Infect Immun. 2012;80(8):2816–2825. doi:10.1128/IAI.00399-12
   PubMed Web of Science ®Google Scholar
• Zhao Y, van Kessel KPM, de Haas CJC, Rogers MRC, van Strijp JAG, Haas PA. Staphylococcal superantigen-like protein 13 activates neutrophils via formyl peptide receptor 2. Cell Microbiol. 2018;20(11):e12941. doi:10.1111/cmi.12941
   Web of Science ®Google Scholar
• Koymans KJ, Goldmann O, Karlsson CAQ, et al. The TLR2 antagonist staphylococcal superantigen-like protein 3 acts as a virulence factor to promote bacterial pathogenicity in vivo. J Innate Immun. 2017;9(6):561–573. doi:10.1159/000479100
   Web of Science ®Google Scholar
• Oku T, Kurisaka C, Ando Y, Tsuji T. Identification of human plasma C1 inhibitor as a target protein for staphylococcal superantigen-like protein 5 (SSL5). Biochem Biophys Res Commun. 2019;508(4):1162–1167. doi:10.1016/j.bbrc.2018.12.026
   Web of Science ®Google Scholar
• Cody V, Pace J, Nawar HF, et al. Structure-activity correlations of variant forms of the B pentamer of Escherichia coli type II heat-labile enterotoxin LT-IIb with Toll-like receptor 2 binding. Acta Crystallogr D Biol Crystallogr. 2012;68(Pt 12):1604–1612. doi:10.1107/S0907444912038917
   Google Scholar
• Okano M, Fujiwara T, Haruna T, et al. Prostaglandin E(2) suppresses staphylococcal enterotoxin-induced eosinophilia-associated cellular responses dominantly through an E-prostanoid 2-mediated pathway in nasal polyps. J Allergy Clin Immunol. 2009;123(4):868–874.e813. doi:10.1016/j.jaci.2009.01.047
   PubMed Web of Science ®Google Scholar
• Zhang A, Dong Z, Yang T. Prostaglandin D2 inhibits TGF-beta1-induced epithelial-to-mesenchymal transition in MDCK cells. Am J Physiol Renal Physiol. 2006;291(6):F1332–1342. doi:10.1152/ajprenal.00131.2006
   PubMed Web of Science ®Google Scholar
• Honda K, Marquillies P, Capron M, Dombrowicz D. Peroxisome proliferator-activated receptor gamma is expressed in airways and inhibits features of airway remodeling in a mouse asthma model. J Allergy Clin Immunol. 2004;113(5):882–888. doi:10.1016/j.jaci.2004.02.036
   PubMed Web of Science ®Google Scholar
• Asaka C, Honda K, Ito E, Fukui N, Chihara J, Ishikawa K. Peroxisome proliferator-activated receptor-γ is expressed in eosinophils in nasal polyps. Int Arch Allergy Immunol. 2011;155 Suppl 1:57–63. doi:10.1159/000327294
   Web of Science ®Google Scholar
• Xu X, Reitsma S, Wang Y, Fokkens WJ. Highlights in the advances of chronic rhinosinusitis. Allergy. 2021;76(11):3349–3358. doi:10.1111/all.14892
   PubMed Web of Science ®Google Scholar
• Neveu WA, Allard JB, Dienz O, et al. IL-6 is required for airway mucus production induced by inhaled fungal allergens. J Immunol. 2009;183(3):1732–1738. doi:10.4049/jimmunol.0802923
   PubMed Web of Science ®Google Scholar
• Bautista MV, Chen Y, Ivanova VS, Rahimi MK, Watson AM, Rose MC. IL-8 regulates mucin gene expression at the posttranscriptional level in lung epithelial cells12. J Immunol. 2009;183(3):2159–2166. doi:10.4049/jimmunol.0803022
   Web of Science ®Google Scholar
• Maares M, Keil C, Straubing S, Robbe-Masselot C, Haase H. Zinc Deficiency Disturbs Mucin Expression, O-Glycosylation and Secretion by Intestinal Goblet Cells. Int J Mol Sci. 2020;21(17):6149. doi:10.3390/ijms21176149
   Web of Science ®Google Scholar
• Valle Arevalo A, Nobile CJ. Interactions of microorganisms with host mucins: a focus on Candida albicans. FEMS Microbiol Rev. 2020;44(5):645–654. doi:10.1093/femsre/fuaa027
   PubMed Web of Science ®Google Scholar
• den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res. 2013;54(9):2325–2340. doi:10.1194/jlr.R036012
   PubMed Web of Science ®Google Scholar
• Mao YJ, Chen HH, Wang B, Liu X, Xiong GY. Increased expression of MUC5AC and MUC5B promoting bacterial biofilm formation in chronic rhinosinusitis patients. Auris Nasus Larynx. 2015;42(4):294–298. doi:10.1016/j.anl.2014.12.004
   PubMed Web of Science ®Google Scholar
• Lucas SK, Villarreal AR, Ahmad MM, et al. Anaerobic microbiota derived from the upper airways impact staphylococcus aureus physiology. Infect Immun. 2021;89(9):e0015321. doi:10.1128/IAI.00153-21
   Web of Science ®Google Scholar
• Fletcher JR, Villareal AR, Penningroth MR, Hunter RC. Staphylococcus aureus Overcomes Anaerobe-Derived Short-Chain Fatty Acid Stress via FadX and the CodY Regulon. J Bacteriol. 2022;204(5):e00064–00022. doi:10.1128/jb.00064-22
   Web of Science ®Google Scholar
• Meissner S, Hagen F, Deiner C, et al. Key role of short-chain fatty acids in epithelial barrier failure during ruminal acidosis. J Dairy Sci. 2017;100(8):6662–6675. doi:10.3168/jds.2016-12262
   PubMed Web of Science ®Google Scholar
• Yuan X, Tang H, Wu R, et al. Short-Chain fatty acids calibrate RARα activity regulating food sensitization. Front Immunol. 2021;2021:12.
   Google Scholar
• Cait A, Hughes MR, Antignano F, et al. Microbiome-driven allergic lung inflammation is ameliorated by short-chain fatty acids. Mucosal Immunol. 2018;11(3):785–795. doi:10.1038/mi.2017.75
   PubMed Web of Science ®Google Scholar
• Bortolotti P, Hennart B, Thieffry C, et al. Tryptophan catabolism in Pseudomonas aeruginosa and potential for inter-kingdom relationship. BMC Microbiol. 2016;16(1):137. doi:10.1186/s12866-016-0756-x
   Google Scholar
• Patnaude L, Mayo M, Mario R, et al. Mechanisms and regulation of IL-22-mediated intestinal epithelial homeostasis and repair. Life Sci. 2021;271:119195. doi:10.1016/j.lfs.2021.119195
   PubMed Web of Science ®Google Scholar
• Linden SK, Sutton P, Karlsson NG, Korolik V, McGuckin MA. Mucins in the mucosal barrier to infection. Mucosal Immunol. 2008;1(3):183–197. doi:10.1038/mi.2008.5
   PubMed Web of Science ®Google Scholar
• Seshadri S, Lin DC, Rosati M, et al. Reduced expression of antimicrobial PLUNC proteins in nasal polyp tissues of patients with chronic rhinosinusitis. Allergy. 2012;67(7):920–928. doi:10.1111/j.1398-9995.2012.02848.x
   PubMed Web of Science ®Google Scholar
• Tarran R, Redinbo MR. Mammalian short palate lung and nasal epithelial clone 1 (SPLUNC1) in pH-dependent airway hydration. Int J Biochem Cell Biol. 2014;52:130–135. doi:10.1016/j.biocel.2014.03.002
   Web of Science ®Google Scholar
• Di YP. Functional roles of SPLUNC1 in the innate immune response against Gram-negative bacteria. Biochem Soc Trans. 2011;39(4):1051–1055. doi:10.1042/BST0391051
   PubMedGoogle Scholar
• Garcia-Caballero A, Rasmussen JE, Gaillard E, et al. SPLUNC1 regulates airway surface liquid volume by protecting ENaC from proteolytic cleavage. Proc Natl Acad Sci. 2009;106(27):11412–11417. doi:10.1073/pnas.0903609106
   PubMed Web of Science ®Google Scholar
• Zeissig S, Fromm A, Mankertz J, et al. Butyrate induces intestinal sodium absorption via Sp3-mediated transcriptional up-regulation of epithelial sodium channels. Gastroenterology. 2007;132(1):236–248. doi:10.1053/j.gastro.2006.10.033
   Web of Science ®Google Scholar
• Ahmad S, Kim CSK, Tarran R. The SPLUNC1-βENaC complex prevents Burkholderia cenocepacia invasion in normal airway epithelia. Respir Res. 2020;21(1):190. doi:10.1186/s12931-020-01454-5
   Google Scholar
• Jiang D, Wenzel SE, Wu Q, Bowler RP, Schnell C, Chu HW. Human neutrophil elastase degrades SPLUNC1 and impairs airway epithelial defense against bacteria. PLoS One. 2013;8:5.
   Web of Science ®Google Scholar
• Keir HR, Shoemark A, Huang JTJ, Chalmers JD. SPLUNC1 is a novel marker of disease severity and airway infection in bronchiectasis. Eur Respir J. 2021;58(5). doi:10.1183/13993003.01840-2021
   Web of Science ®Google Scholar
• Khanal S, Webster M, Niu N, et al. SPLUNC1: a novel marker of cystic fibrosis exacerbations. Eur Respir J. 2021;58(5). doi:10.1183/13993003.00507-2020
   Web of Science ®Google Scholar
• Terryah ST, Fellner RC, Ahmad S, et al. Evaluation of a SPLUNC1-derived peptide for the treatment of cystic fibrosis lung disease. Am J Physiol Lung Cell Mol Physiol. 2018;314(1):L192–l205. doi:10.1152/ajplung.00546.2016
   PubMed Web of Science ®Google Scholar
• Huang Y, Wang M, Hong Y, et al. Reduced expression of antimicrobial protein secretory leukoprotease inhibitor and clusterin in chronic rhinosinusitis with nasal polyps. J Immunol Res. 2021;2021:1057186. doi:10.1155/2021/1057186
   PubMed Web of Science ®Google Scholar
• Tsou Y-A, Lin C-D, Chen H-C, et al. Interleukin-13 inhibits lipopolysaccharide-induced BPIFA1 expression in nasal epithelial cells. PLoS One. 2015;10:e0143484.
   PubMedGoogle Scholar
• Bae CH, Na HG, Choi YS, Song SY, Kim YD. Clusterin induces MUC5AC expression via activation of NF-κB in human airway epithelial cells. Clin Exp Otorhinolaryngol. 2018;11(2):124–132. doi:10.21053/ceo.2017.00493
   Web of Science ®Google Scholar
• De Corso E, Baroni S, Onori ME, et al. Calprotectin in nasal secretion: a new biomarker of non-type 2 inflammation in CRSwNP. Acta Otorhinolaryngol Ital. 2022;42(4):355–363. doi:10.14639/0392-100X-N1800
   Web of Science ®Google Scholar
• Sumsion JS, Pulsipher A, Alt JA. Differential expression and role of S100 proteins in chronic rhinosinusitis. Curr Opin Allergy Clin Immunol. 2020;20(1):14–22. doi:10.1097/ACI.0000000000000595
   Web of Science ®Google Scholar
• Viksne RJ, Sumeraga G, Pilmane M. Antimicrobial and defense proteins in chronic rhinosinusitis with nasal polyps. Medicina. 2023;59(7):1259. doi:10.3390/medicina59071259
   Google Scholar
• Tieu DD, Peters AT, Carter RG, et al. Evidence for diminished levels of epithelial psoriasin and calprotectin in chronic rhinosinusitis. J Allergy Clin Immunol. 2010;125(3):667–675. doi:10.1016/j.jaci.2009.11.045
   PubMed Web of Science ®Google Scholar
• Isaksen B, Fagerhol MK. Calprotectin inhibits matrix metalloproteinases by sequestration of zinc. Mol Pathol. 2001;54(5):289–292. doi:10.1136/mp.54.5.289
   Google Scholar
• Sroussi HY, Lu Y, Villines D, Sun Y. The down regulation of neutrophil oxidative metabolism by S100A8 and S100A9: implication of the protease-activated receptor-2. Mol Immunol. 2012;50(1–2):42–48. doi:10.1016/j.molimm.2011.12.001
   Web of Science ®Google Scholar
• Kehl-Fie Thomas E, Chitayat S, Hood MI, et al. Nutrient metal sequestration by calprotectin inhibits bacterial superoxide defense, enhancing neutrophil killing of staphylococcus aureus. Cell Host Microbe. 2011;10(2):158–164. doi:10.1016/j.chom.2011.07.004
   Web of Science ®Google Scholar
• Obisesan AO, Zygiel EM, Nolan EM. Bacterial responses to iron withholding by calprotectin. Biochemistry. 2021;60(45):3337–3346. doi:10.1021/acs.biochem.1c00572
   Web of Science ®Google Scholar
• Wakeman CA, Moore JL, Noto MJ, et al. The innate immune protein calprotectin promotes Pseudomonas aeruginosa and Staphylococcus aureus interaction. Nat Commun. 2016;7:11951. doi:10.1038/ncomms11951
   PubMed Web of Science ®Google Scholar
• Wang J, Lonergan ZR, Gonzalez-Gutierrez G, et al. Multi-metal restriction by calprotectin impacts de novo flavin biosynthesis in Acinetobacter baumannii. Cell Chem Biol. 2019;26(5):745–755.e747. doi:10.1016/j.chembiol.2019.02.011
   Web of Science ®Google Scholar
• Gaddy JA, Radin JN, Cullen TW, et al. Helicobacter pylori resists the antimicrobial activity of calprotectin via lipid a modification and associated biofilm formation. MBio. 2015;6(6). doi:10.1128/mBio.01349-15
   Web of Science ®Google Scholar
• Rosen T, Hadley RC, Bozzi AT, Ocampo D, Shearer J, Nolan EM. Zinc sequestration by human calprotectin facilitates manganese binding to the bacterial solute-binding proteins PsaA and MntC. Metallomics. 2022;14(2). doi:10.1093/mtomcs/mfac001
   Web of Science ®Google Scholar
• Kwah JH, Peters AT. Nasal polyps and rhinosinusitis. Allergy Asthma Proc. 2019;40(6):380–384. doi:10.2500/aap.2019.40.4252
   Web of Science ®Google Scholar
• Ta NH. Will we ever cure nasal polyps? Ann R Coll Surg Engl. 2019;101(1):35–39. doi:10.1308/rcsann.2018.0149
   Web of Science ®Google Scholar
• Eloy P, Poirrier AL, De Dorlodot C, Van Zele T, Watelet JB, Bertrand B. Actual concepts in rhinosinusitis: a review of clinical presentations, inflammatory pathways, cytokine profiles, remodeling, and management. Curr Allergy Asthma Rep. 2011;11(2):146–162. doi:10.1007/s11882-011-0180-0
   Web of Science ®Google Scholar
• Goulioumis AK, Kourelis K, Gkorpa M, Danielides V. Pathogenesis of Nasal Polyposis: current Trends. Indian J Otolaryngol Head Neck Surg. 2023;75(Suppl S1):733–741. doi:10.1007/s12070-022-03247-2
   Web of Science ®Google Scholar
• Headland SE, Dengler HS, Xu D, et al. Oncostatin M expression induced by bacterial triggers drives airway inflammatory and mucus secretion in severe asthma. Sci Transl Med. 2022;14(627):eabf8188. doi:10.1126/scitranslmed.abf8188
   Web of Science ®Google Scholar
• Nosrati R, Kheirouri S, Ghodsi R, Ojaghi H. The effects of zinc treatment on matrix metalloproteinases: a systematic review. J Trace Elem Med Biol. 2019;56:107–115. doi:10.1016/j.jtemb.2019.08.001
   Web of Science ®Google Scholar
• Van Zele T, Gevaert P, Watelet JB, et al. Staphylococcus aureus colonization and IgE antibody formation to enterotoxins is increased in nasal polyposis. J Allergy Clin Immunol. 2004;114(4):981–983. doi:10.1016/j.jaci.2004.07.013
   PubMed Web of Science ®Google Scholar
• Seiberling KA, Conley DB, Tripathi A, et al. Superantigens and chronic rhinosinusitis: detection of staphylococcal exotoxins in nasal polyps. Laryngoscope. 2005;115(9):1580–1585. doi:10.1097/01.mlg.0000168111.11802.9c
   Web of Science ®Google Scholar
• Chen JB, James LK, Davies AM, et al. Antibodies and superantibodies in patients with chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol. 2017;139(4):1195–1204.e1111. doi:10.1016/j.jaci.2016.06.066
   PubMed Web of Science ®Google Scholar
• Yan G, Lei H, He M, et al. Melatonin triggers autophagic cell death by regulating RORC in Hodgkin lymphoma. Biomed Pharmacother. 2020;123:109811. doi:10.1016/j.biopha.2020.109811
   Web of Science ®Google Scholar
• Eberl G. RORγt, a multitask nuclear receptor at mucosal surfaces. Mucosal Immunol. 2017;10(1):27–34. doi:10.1038/mi.2016.86
   Web of Science ®Google Scholar
• Oh TG, Wang SM, Acharya BR, et al. The nuclear receptor, RORγ, regulates pathways necessary for breast cancer metastasis. EBioMedicine. 2016;6:59–72. doi:10.1016/j.ebiom.2016.02.028
   Web of Science ®Google Scholar
• Hinic V, Lang C, Weisser M, Straub C, Frei R, Goldenberger D. Corynebacterium tuberculostearicum: a potentially misidentified and multiresistant Corynebacterium species isolated from clinical specimens. J Clin Microbiol. 2012;50(8):2561–2567. doi:10.1128/JCM.00386-12
   Web of Science ®Google Scholar
• Succar EF, Turner JH. Recent advances in understanding chronic rhinosinusitis endotypes. F1000Res. 2018;7. doi:10.12688/f1000research.16222.1
   Google Scholar
• Weinrick B, Dunman PM, McAleese F, et al. Effect of mild acid on gene expression in staphylococcus aureus. J Bacteriol. 2004;186(24):8407–8423. doi:10.1128/JB.186.24.8407-8423.2004
   PubMed Web of Science ®Google Scholar
• Yang X, Dong F, Qian S, et al. Accessory gene regulator (agr) dysfunction was unusual in Staphylococcus aureus isolated from Chinese children. BMC Microbiol. 2019;19(1):95. doi:10.1186/s12866-019-1465-z
   Google Scholar
• Shopsin B, Drlica-Wagner A, Mathema B, Adhikari RP, Kreiswirth BN, Novick RP. Prevalence of agr dysfunction among colonizing Staphylococcus aureus strains. J Infect Dis. 2008;198(8):1171–1174. doi:10.1086/592051
   PubMed Web of Science ®Google Scholar
• Boles BR, Horswill AR. Agr-mediated dispersal of Staphylococcus aureus biofilms. PLoS Pathogens. 2008;4(4):e1000052. doi:10.1371/journal.ppat.1000052
   PubMed Web of Science ®Google Scholar
• Tan L, Li SR, Jiang B, Hu XM, Li S. Therapeutic targeting of the staphylococcus aureus accessory gene regulator (agr) System. Front Microbiol. 2018;9:55. doi:10.3389/fmicb.2018.00055
   PubMed Web of Science ®Google Scholar
• Gao K, Mu CL, Farzi A, Zhu WY. Tryptophan metabolism: a link between the gut microbiota and brain. Adv Nutr. 2020;11(3):709–723. doi:10.1093/advances/nmz127
   PubMed Web of Science ®Google Scholar
• Quinn GA, Cole AM. Suppression of innate immunity by a nasal carriage strain of Staphylococcus aureus increases its colonization on nasal epithelium. Immunology. 2007;122(1):80–89. doi:10.1111/j.1365-2567.2007.02615.x
   PubMed Web of Science ®Google Scholar
• Wu C, Chen YW, Scheible M, et al. Genetic and molecular determinants of polymicrobial interactions in Fusobacterium nucleatum. Proc Natl Acad Sci U S A. 2021;118:23.
   Web of Science ®Google Scholar
• de Steenhuijsen Piters WA, Sanders EA, Bogaert D. The role of the local microbial ecosystem in respiratory health and disease. Philos Trans R Soc London Series B Biol Sci. 2015;370:1675.
   Web of Science ®Google Scholar
• Mårtensson A, Cervin-Hoberg C, Huygens F, et al. Upper airway microbiome transplantation for patients with chronic rhinosinusitis. Int Forum Allergy Rhinol. 2023;13(6):979–988. doi:10.1002/alr.23122
   Web of Science ®Google Scholar
• Nath S, Zilm P, Jamieson L, et al. Development and characterization of an oral microbiome transplant among Australians for the treatment of dental caries and periodontal disease: a study protocol. PLoS One. 2021;16(11):e0260433. doi:10.1371/journal.pone.0260433
   PubMed Web of Science ®Google Scholar
• Nascimento MM. Oral microbiota transplant: a potential new therapy for oral diseases. J Calif Dent Assoc. 2017;45(10):565–568. doi:10.1080/19424396.2017.12222506
   PubMedGoogle Scholar
• Beikler T, Bunte K, Chan Y, et al. Oral microbiota transplant in dogs with naturally occurring periodontitis. J Dent Res. 2021;100(7):764–770. doi:10.1177/0022034521995423
   PubMed Web of Science ®Google Scholar