title: Alteration of local microflora and α-defensins hyper-production in colonic adenoma mucosa.
abstract: OBJECTIVE
  Gut flora/host interactions are fundamental for the maintenance of homeostasis. Evidence of possible regulatory effect of commensal bacteria on proliferative disorders of the colon is mounting. In this study, we explored the hypothesis that precancerous lesions, such as adenomas, present alteration of the local microflora and lead to an overproduction of antibacterial molecules of the innate immunity, namely α-defensins. Thus, the host-bacteria misbalance could represent a potential procarcinogenic factor.
  
  
  METHODS
  Biopsies from adenomatous polyps and normal mucosa, in the rectum-sigmoid colon, were collected from 51 patients. Concentration of mucosal bacteria was evaluated by real-time polymerase chain reaction after extraction of total DNA. Total RNA was also extracted, and the defensin α-1, defensin-5, and defensin-6 gene expressions were evaluated by real-time polymerase chain reaction. Immunohistochemical study has been carried out to evaluate protein production and location. Antibacterial activity of adenomatous polyps mucosa was evaluated in vitro.
  
  
  RESULTS
  Biopsies from adenomatous polyps had a significant relative reduction of mucosa adherent bacteria compared with normal tissue (20-fold relative reduction, P<0.05). Concomitantly, α-defensin expression and production were significantly increased in adenomas. Adenoma mucosa showed increased antibacterial activity in vitro compared with normal mucosa.
  
  
  CONCLUSIONS
  Microflora dysbiosis occurs at the mucosal surface in colonic adenomas, and may represent a potential factor for dysplastic cell proliferation. Further studies are needed to confirm and define the role of this mechanism in colon carcinogenesis and the potential applications in the clinical setting.
authors.affiliation: Digestive and Liver Disease Unit, II Faculty of Medicine, University of Rome La Sapienza, S. Andrea Hospital, Rome, Italy. cristiano.pagnini@uniroma1.it
authors.forename: Cristiano
authors.initials: C
authors.lastname: Pagnini
authors.forename: Vito D
authors.initials: VD
authors.lastname: Corleto
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Mangoni
authors.forename: Emanuela
authors.initials: E
authors.lastname: Pilozzi
authors.forename: Maria Simona
authors.initials: MS
authors.lastname: Torre
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Marchese
authors.forename: Antonella
authors.initials: A
authors.lastname: Carnuccio
authors.forename: Emilio Di
authors.initials: ED
authors.lastname: Giulio
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Delle Fave
mesh_terms: D000236:Adenoma / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D001419:Bacteria / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D001706:Biopsy; D003106:Colon / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D003110:Colonic Neoplasms / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D003111:Colonic Polyps / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D004269:DNA, Bacterial / Q000032:analysis; D006801:Humans; D007113:Immunity, Innate; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D008826:Microbial Sensitivity Tests; D016133:Polymerase Chain Reaction; D015854:Up-Regulation; D023084:alpha-Defensins / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D004269:DNA, Bacterial; D023084:alpha-Defensins