Background and Aim: 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 alpha-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 alpha-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, alpha-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.

Alteration of local microflora and α-defensins hyper-production in colonic adenoma mucosa / Pagnini, Cristiano; Corleto, Vito Domenico; Mangoni, Maria Luisa; Pilozzi, Emanuela; Maria Simona, Torre; Rodolfo, Marchese; Antonella, Carnuccio; DI GIULIO, Emilio; DELLE FAVE, Gianfranco; Giulio, Ed; Gianfranco Delle, Fave. - In: JOURNAL OF CLINICAL GASTROENTEROLOGY. - ISSN 0192-0790. - STAMPA. - 45:7(2011), pp. 602-610. [10.1097/mcg.0b013e31820abf29]

Alteration of local microflora and α-defensins hyper-production in colonic adenoma mucosa

PAGNINI, Cristiano;CORLETO, Vito Domenico;MANGONI, Maria Luisa;PILOZZI, Emanuela;DI GIULIO, Emilio;DELLE FAVE, Gianfranco;
2011

Abstract

Background and Aim: 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 alpha-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 alpha-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, alpha-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.
2011
α-defensin; alpha-defensin; carcinogenesis; adenoma; colon; microbiota
01 Pubblicazione su rivista::01a Articolo in rivista
Alteration of local microflora and α-defensins hyper-production in colonic adenoma mucosa / Pagnini, Cristiano; Corleto, Vito Domenico; Mangoni, Maria Luisa; Pilozzi, Emanuela; Maria Simona, Torre; Rodolfo, Marchese; Antonella, Carnuccio; DI GIULIO, Emilio; DELLE FAVE, Gianfranco; Giulio, Ed; Gianfranco Delle, Fave. - In: JOURNAL OF CLINICAL GASTROENTEROLOGY. - ISSN 0192-0790. - STAMPA. - 45:7(2011), pp. 602-610. [10.1097/mcg.0b013e31820abf29]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/365383
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