CIRRHOSIS AND LIVER FAILURE Protective effect of Bifidobacterium pseudocatenulatum CECT7765 against induced bacterial antigen translocation in experimental cirrhosis Alba Moratalla 1,2 , Isabel G omez-Hurtado 1,2 , Arlette Santacruz 3 ,  Angela Moya 3 , Gloria Peir  o 4 , Pedro Zapater 1,5 , Jos e M. Gonz alez-Navajas 1,2 , Paula Gim enez 1 , Jos e Such 1,2,6 , Yolanda Sanz 3 and Rub en Franc es 1,2,6 1 CIBERehd, Instituto de Salud Carlos III, Madrid, Spain 2 Unidad Hep atica, Consejo Superior de Investigaciones Cient  ıficas (IATA-CSIC), Valencia, Spain 3 Ecolog  ıa Microbiana y Nutrici  on, Instituto de Agroqu  ımica y Tecnolog  ıa de Alimentos, Consejo Superior de Investigaciones Cient  ıficas (IATA-CSIC), Valencia, Spain 4 Servicio de Anatom  ıa Patol ogica, Hospital General Universitario de Alicante, Alicante, Spain 5 Unidad de Farmacolog  ıa Cl  ınica, Hospital General Universitario de Alicante, Alicante, Spain 6 Facultad de Medicina, Departamento de Medicina Cl  ınica, Universidad Miguel Hern andez, San Juan de Alicante, Spain Keywords B. pseudocatenulatum CECT7765 – bacterial translocation – cirrhosis – inflammation – microbiota Correspondence Rub en Franc es, PhD., CIBERehd-Liver Unit, Hospital General Universitario de Alicante, Avda. Pintor Baeza 12, 03010 Alicante, Spain Tel: +34 965 913 928 Fax: +34 965 913 922 e-mail: frances_rub@gva.es Received 16 July 2013 Accepted 31 October 2013 DOI:10.1111/liv.12380 Abstract Background & Aims: Intervention in the gut ecosystem is considered as a potential strategy to treat liver diseases and their complications. We have evaluated the effects of Bifidobacterium pseudocatenulatum CECT7765 on bacterial translocation and the liver status in experimental cirrhosis. Animals & Methods: Liver damage was induced in Balb/c mice by weight-controlled oral administration of carbon tetrachloride. Laparotomies were performed at week 12. One week prior to laparotomy, animals received B. pseudocatenula- tum CECT7765 (10 9 cfu/daily) or placebo intragastrically. All animals received Escherichia coli (10 7 cfu/single dose) intragastrically 24 hours before laparotomy. A group of na € ıve non-treated animals was included as control. Liver tissue specimens, mesenteric lymph nodes, intestinal content and blood were collected. Liver histology, profibrogenic genes expression, bacterial DNA translocation, serum endotoxaemia and liver cytokine levels were mea- sured. Results: Bifidobacterium pseudocatenulatum CECT7765 showed no significant effect on structural liver damage, as determined by histological evaluation, alpha-smooth muscle actin distribution, profibrogenic gene expression levels, total hydroxyproline levels and malon dialdehyde produc- tion compared with mice receiving placebo. Interestingly, bacterial DNA translocation and serum endotoxin levels were significantly decreased in mice receiving the Bifidobacterium strain compared with placebo. Gut barrier integrity markers were up-regulated in mice receiving B. pseudocatenulatum CECT7765 and quantitatively correlated with intestinal gene copy numbers of the bifidobacterial strain. Gene expression levels of several anti-inflamma- tory mediators were also increased in mice receiving B. pseudocatenulatum CECT7765 compared with placebo. Conclusion: Oral administration of B. pseudocatenulatum CECT7765 is associated with improved gut barrier integ- rity and shows a beneficial effect against induced bacterial antigen transloca- tion in the CCl 4 -model of cirrhosis. Translocation of bacteria or their products (BT) from the intestinal lumen to the mesenteric lymph nodes (MLNs) has been extensively documented as a frequent complication in cirrhosis, not only at end-stage but also in early stages of disease progression (1, 2). Mechanisms proposed to explain these bacterial translocation epi- sodes include an increased intestinal permeability (3–5), an intestinal bacterial overgrowth (IBO) (6–8) and, more recently, alterations in the gut microbiota compo- sition (9, 10), which might contribute to increasing the liver exposure to microbial products and inflammatory signals coming from the gut. Therefore, the communi- cation between the gut and the liver, the so-called gut- liver axis, is thought to be involved in cirrhosis, being gut microbiota a key regulator of inflammation and BT in this setting (11). Consequently, probiotics have Liver International (2013) © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 1 Liver International ISSN 1478-3223