Browsing by Author "Kofonow, Jennifer M."

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    A Dysbiotic Microbiome Promotes Head and Neck Squamous Cell Carcinoma
    (Springer Nature, 2022) Frank, Daniel N.; Qiu, Yue; Cao, Yu; Zhang, Shuguang; Lu, Ling; Kofonow, Jennifer M.; Robertson, Charles E.; Liu, Yanqiu; Wang, Haibo; Levens, Cassandra L.; Kuhn, Kristi A.; Song, John; Ramakrishnan, Vijay R.; Lu, Shi-Long; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Recent studies have reported dysbiotic oral microbiota and tumor-resident bacteria in human head and neck squamous cell carcinoma (HNSCC). We aimed to identify and validate oral microbial signatures in treatment-naïve HNSCC patients compared with healthy control subjects. We confirm earlier reports that the relative abundances of Lactobacillus spp. and Neisseria spp. are elevated and diminished, respectively, in human HNSCC. In parallel, we examined the disease-modifying effects of microbiota in HNSCC, through both antibiotic depletion of microbiota in an induced HNSCC mouse model (4-Nitroquinoline 1-oxide, 4NQO) and reconstitution of tumor-associated microbiota in a germ-free orthotopic mouse model. We demonstrate that depletion of microbiota delays oral tumorigenesis, while microbiota transfer from mice with oral cancer accelerates tumorigenesis. Enrichment of Lactobacillus spp. was also observed in murine HNSCC, and activation of the aryl-hydrocarbon receptor was documented in both murine and human tumors. Together, our findings support the hypothesis that dysbiosis promotes HNSCC development.
  • Thumbnail Image
    Item
    Altered Tissue Specialized Pro-Resolving Mediators in Chronic Rhinosinusitis
    (Elsevier, 2021) Vickery, Thad W.; Armstrong, Michael; Kofonow, Jennifer M.; Robertson, Charles E.; Kroehl, Miranda E.; Reisdorph, Nichole A.; Ramakrishnan, Vijay R.; Frank, Daniel N.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Current literature implicates arachidonic acid-derived leukotrienes and prostaglandins in the pathogenesis of chronic rhinosinusitis. However, other omega-3 and omega-6 derived lipid mediators, such as specialized pro-resolving mediators (SPMs), may also be important in chronic inflammatory disorders of the upper airway. We hypothesize that SPMs differ among CRS subtypes compared to controls and in relation to sinonasal microbiota. Ethmoid sinus tissue and middle meatal swabs were collected from a convenience sample of 66 subjects, including non-CRS controls, CRS with polyps (CRSwNP), and CRS without polyps (CRSsNP). Lipid mediator pathways were analyzed by liquid chromatography/tandem mass spectrometry. Bacterial taxa were profiled in parallel by 16S rRNA gene sequencing. Resolvin D2 was elevated in both CRSwNP (p = 0.00076) and CRSsNP (p = 0.030) compared with non-CRS controls. Lipoxin A4 was significantly increased in CRSwNP compared with CRSsNP (p = 0.000033) and controls (p = 0.044). Cigarette smoking was associated with significantly lower concentrations of several 15-lipoxygenase metabolites including resolvin D1 (p = 0.0091) and resolvin D2 (p = 0.0097), compared with never-smokers. Several of the lipid compounds also correlated with components of the sinonasal mucosal microbiota, including bacterial pathogens such as Pseudomonas aeruginosa. These data suggest that dysfunctional lipid mediator pathways in CRS extend beyond the traditional descriptions of leukotrienes and prostaglandins and include SPMs. Furthermore, dysregulated SPM signaling may contribute to persistent inflammation and bacterial colonization in CRS.
  • Thumbnail Image
    Item
    Specialized pro-resolving mediator lipidome and 16S rRNA bacterial microbiome data associated with human chronic rhinosinusitis
    (Elsevier, 2021-04-01) Vickery, Thad W.; Armstrong, Michael; Kofonow, Jennifer M.; Robertson, Charles E.; Kroehl, Miranda E.; Reisdorph, Nichole A.; Ramakrishnan, Vijay R.; Frank, Daniel N.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Chronic rhinosinusitis (CRS) is a clinical syndrome defined by symptoms including nasal congestion, facial pain and pressure, anosmia, and rhinorrhea lasting more than 12 weeks. Several mechanistically distinct processes lead to the development of clinical symptoms in CRS including innate immune dysfunction, dysregulated eicosanoid metabolism and perturbations in host-microbiome interactions [1]. We developed a database comprised of patient demographic information, lipid mediator metabolomic profiles, and 16S bacterial rRNA gene sequence data from 66 patients undergoing endoscopic sinus surgery. Briefly, ethmoid sinus tissue and middle meatal swabs were collected from patients, including non-CRS controls, CRS with polyps (CRSwNP), and CRS without polyps (CRSsNP). Lipid mediator pathways from arachidonic acid (AA) and docosahexanoic acid (DHA) were analyzed by liquid chromatography/tandem mass spectrometry. Bacterial taxa were profiled in parallel by 16S rRNA gene sequencing. This database provides a useful compendium of AA/DHA metabolomic profiles and associated bacterial microbiota in patients with varying disease subtypes, demographics, and risk factors/comorbidities.