title: Topical probiotics as a therapeutic alternative for chronic rhinosinusitis: A preclinical proof of concept.
abstract: BACKGROUND
  Patients with chronic rhinosinusitis (CRS) have been shown to manifest a high inflammatory phenotype, with a sinus microbiome deficient in gram-positive bacteria. Gram-positive bacteria are capable of downregulating proinflammatory host responses via an interleukin (IL) 10 mediated response and may represent a potential therapeutic alternative for CRS. We wanted to (i) immunoprofile the IL-10 induction capacity of two gram-positive probiotic strains and (ii) verify the tolerance of these strains by the sinus epithelium.
  
  
  METHODS
  A peripheral blood mononuclear cell (PBMC) challenge model was used to document probiotic induction of IL-10 and tumor necrosis factor (TNF) alpha responses at various bacterial dilutions. Epithelial cell tolerance was demonstrated by using a primary epithelial cell model derived from patient biopsy specimens (six patients total [three with CRS and three controls]). After an incubation period with either a live or a heat-killed probiotic strain, cell viability was assessed by using light microscopy.
  
  
  RESULTS
  Both probiotic strains induced high IL-10 secretion in PBMCs, with differing profiles of TNF alpha production. Microscopic evaluation after probiotic incubation demonstrated intact cell viability for all cell cultures.
  
  
  CONCLUSIONS
  We identified well-tolerated, nonpathogenic, "generally recognized as safe" status gram-positive probiotics with anti-inflammatory properties. Topical probiotics represented a potential novel topical therapeutic strategy for CRS relevant for further clinical evaluation.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, McGill University, Montreal, Canada.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Schwartz
authors.forename: Adam G
authors.initials: AG
authors.lastname: Peres
authors.forename: Leandra
authors.initials: L
authors.lastname: Mfuna Endam
authors.forename: Benoit
authors.initials: B
authors.lastname: Cousineau
authors.forename: Joaquin
authors.initials: J
authors.lastname: Madrenas
authors.forename: Martin
authors.initials: M
authors.lastname: Desrosiers
mesh_terms: D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002478:Cells, Cultured; D002908:Chronic Disease; D004353:Drug Evaluation, Preclinical; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000382:microbiology; D064307:Microbiota; D061251:Primary Cell Culture; D019936:Probiotics / Q000032:analysis* / Q000627:therapeutic use; D012220:Rhinitis / Q000382:microbiology / Q000628:therapy*; D012852:Sinusitis / Q000382:microbiology / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10