Accepted Article
Received Date : 12-Feb-2014 Revised Date : 28-Mar-2014 Accepted Date : 17-Apr-2014 Article type
: Original Articles
TITLE PAGE
TITLE VSL#3 PROBIOTIC TREATMENT DECREASES BACTERIAL TRANSLOCATION IN RATS WITH CARBON TETRACHLORIDE-INDUCED CIRRHOSIS
RUNNING HEAD PROBIOTICS IN EXPERIMENTAL CIRRHOSIS
AUTHORS Elisabet Sánchez1,6,8,9*, Juan Camilo Nieto2,6,9*, Ana Boullosa7, Silvia Vidal2,6,9, Francesc Josep Sancho4, Giacomo Rossi10, Pau Sancho-Bru7,8, Rosa Oms5, Beatriz Mirelis3,9, Cándido Juárez2,9, Carlos Guarner1,6,8,9, Germán Soriano1,6,8,9
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/liv.12566 This article is protected by copyright. All rights reserved.
Accepted Article
AFFILIATIONS 1
Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona,
Spain 2
Department of Immunology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
3
Department of Microbiology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
4
Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
5
Department of Biochemistry, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
6
Institut d´Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain
7
Institut Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de
Barcelona, Barcelona, Spain 8
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y
Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain 9
Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain
10
School of Veterinary Medical Sciences, University of Camerino, Camerino, Italy
*The two authors contributed equally to the study
CORRESPONDING AUTHOR German Soriano, MD, PhD Department of Gastroenterology Hospital de la Santa Creu i Sant Pau This article is protected by copyright. All rights reserved.
Accepted Article
Mas Casanovas 90 08041 Barcelona Phone number: 34-93-5565920 Fax number: 34-93-5565608 e-mail: [email protected]
FINANCIAL SUPPORT This study was partially funded by VSL Pharmaceuticals Inc., Towson, MD, USA, and grant PI08/0262 from the Instituto de Salud Carlos III, Madrid, Spain. Silvia Vidal was supported by “Fondo de Investigaciones Sanitarias” and participant in the Program for Stabilization of Investigators of the “Direcció d'Estrategia i Coordinació del Departament de Salut de la Generalitat de Catalunya”. Pau Sancho-Bru is funded by Instituto de Salud Carlos III, Miguel Servet (CP11/00071).
ABSTRACT Background. Probiotics can prevent pathological bacterial translocation in cirrhosis by modulating intestinal microbiota and improving gut barrier and immune disturbances. Aim. To evaluate the effect of probiotic VSL#3 on bacterial translocation, intestinal microbiota, gut barrier and inflammatory response in rats with experimental cirrhosis.
This article is protected by copyright. All rights reserved.
Accepted Article
Methods. Forty-six Sprague-Dawley rats with CCl4-induced cirrhosis were randomized into two groups: VSL#3 group (n=22) that received VSL#3 in drinking water, and water group (n=24) that received water only. Treatment began at week 6 of cirrhosis induction and continued until laparotomy, performed one week after development of ascites or at week 20. A control group included 11 healthy rats. At the study end we evaluated bacterial translocation, intestinal flora, intestinal barrier (ileal claudin-2 and 4, β-defensin-1, occludin and malondialdehyde as index of oxidative damage) and serum cytokines. Results. Mortality during the study was similar in the VSL#3 group (10/22, 45%) and the water group (10/24, 42%) (p=1). The incidence of bacterial translocation was 1/12 (8%) in the VSL#3 group, 7/14 (50%) in the water group 2 (p=0.03 vs VSL#3 group) and 0/11 in the control group (p=0.008 vs water group). The concentration of ileal and cecal enterobacteria and enterococci was similar in the two groups of cirrhotic rats. The ileal occludin concentration was higher and ileal malondialdehyde and serum levels of TNF-α were lower in the VSL#3 group than in the water group (p
Received Date : 12-Feb-2014 Revised Date : 28-Mar-2014 Accepted Date : 17-Apr-2014 Article type
: Original Articles
TITLE PAGE
TITLE VSL#3 PROBIOTIC TREATMENT DECREASES BACTERIAL TRANSLOCATION IN RATS WITH CARBON TETRACHLORIDE-INDUCED CIRRHOSIS
RUNNING HEAD PROBIOTICS IN EXPERIMENTAL CIRRHOSIS
AUTHORS Elisabet Sánchez1,6,8,9*, Juan Camilo Nieto2,6,9*, Ana Boullosa7, Silvia Vidal2,6,9, Francesc Josep Sancho4, Giacomo Rossi10, Pau Sancho-Bru7,8, Rosa Oms5, Beatriz Mirelis3,9, Cándido Juárez2,9, Carlos Guarner1,6,8,9, Germán Soriano1,6,8,9
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/liv.12566 This article is protected by copyright. All rights reserved.
Accepted Article
AFFILIATIONS 1
Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona,
Spain 2
Department of Immunology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
3
Department of Microbiology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
4
Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
5
Department of Biochemistry, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
6
Institut d´Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain
7
Institut Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de
Barcelona, Barcelona, Spain 8
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y
Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain 9
Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain
10
School of Veterinary Medical Sciences, University of Camerino, Camerino, Italy
*The two authors contributed equally to the study
CORRESPONDING AUTHOR German Soriano, MD, PhD Department of Gastroenterology Hospital de la Santa Creu i Sant Pau This article is protected by copyright. All rights reserved.
Accepted Article
Mas Casanovas 90 08041 Barcelona Phone number: 34-93-5565920 Fax number: 34-93-5565608 e-mail: [email protected]
FINANCIAL SUPPORT This study was partially funded by VSL Pharmaceuticals Inc., Towson, MD, USA, and grant PI08/0262 from the Instituto de Salud Carlos III, Madrid, Spain. Silvia Vidal was supported by “Fondo de Investigaciones Sanitarias” and participant in the Program for Stabilization of Investigators of the “Direcció d'Estrategia i Coordinació del Departament de Salut de la Generalitat de Catalunya”. Pau Sancho-Bru is funded by Instituto de Salud Carlos III, Miguel Servet (CP11/00071).
ABSTRACT Background. Probiotics can prevent pathological bacterial translocation in cirrhosis by modulating intestinal microbiota and improving gut barrier and immune disturbances. Aim. To evaluate the effect of probiotic VSL#3 on bacterial translocation, intestinal microbiota, gut barrier and inflammatory response in rats with experimental cirrhosis.
This article is protected by copyright. All rights reserved.
Accepted Article
Methods. Forty-six Sprague-Dawley rats with CCl4-induced cirrhosis were randomized into two groups: VSL#3 group (n=22) that received VSL#3 in drinking water, and water group (n=24) that received water only. Treatment began at week 6 of cirrhosis induction and continued until laparotomy, performed one week after development of ascites or at week 20. A control group included 11 healthy rats. At the study end we evaluated bacterial translocation, intestinal flora, intestinal barrier (ileal claudin-2 and 4, β-defensin-1, occludin and malondialdehyde as index of oxidative damage) and serum cytokines. Results. Mortality during the study was similar in the VSL#3 group (10/22, 45%) and the water group (10/24, 42%) (p=1). The incidence of bacterial translocation was 1/12 (8%) in the VSL#3 group, 7/14 (50%) in the water group 2 (p=0.03 vs VSL#3 group) and 0/11 in the control group (p=0.008 vs water group). The concentration of ileal and cecal enterobacteria and enterococci was similar in the two groups of cirrhotic rats. The ileal occludin concentration was higher and ileal malondialdehyde and serum levels of TNF-α were lower in the VSL#3 group than in the water group (p
