title: Oral probiotic VSL#3 attenuates the circulatory disturbances of patients with cirrhosis and ascites.
abstract: OBJECTIVE
  The modulation of gut flora constitutes a therapeutic tool in patients with liver disease, but some of its modalities require further investigation. Here, we evaluated the effects of probiotics on the hepatic and systemic haemodynamic alterations of advanced liver disease.
  
  
  METHODS
  Seventeen patients with cirrhosis and ascites were prospectively included, five of whom abandoned this study prematurely. Hepatic and systemic haemodynamic evaluations were performed at baseline and after 6 weeks of receiving an oral VSL#3 probiotic preparation. Peripheral blood analyses included the evaluation of cytokines (TNF-alpha, IL-1beta, IL-6), bacterial translocation [bacterial DNA and lipopolysaccharide-binding protein (LBP)] and nitric oxide end-products (NOx).
  
  
  RESULTS
  In 12 patients completing this study, the oral administration of VSL#3 resulted in reductions of the hepatic venous pressure gradient (HVPG, P < 0.001), cardiac index and heart rate (both P < 0.01) and in increases of the systemic vascular resistance (P < 0.05) and mean arterial pressure (P = 0.06). HVPG decreased at least 10% from baseline in eight patients (67%). Serum sodium increased in most patients (P < 0.01). All these changes were unrelated to the detection of bacterial DNA or to the levels of LBP, pro-inflammatory cytokines or NOx. No significant adverse effects were observed.
  
  
  CONCLUSIONS
  Administration of the probiotic mixture VSL#3 improved the hepatic and systemic haemodynamics and serum sodium levels in patients with cirrhosis. Our results identify major effects of probiotics in liver disease and provide the rationale for assessing their therapeutic potential against the progression of portal hypertension and its complications in future clinical trials.
authors.affiliation: Medicina-Ap. Digestivo, Hospital General Universitario Gregorio Marañón - CIBERehd - IiSGM., Madrid, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Rincón
authors.forename: Javier
authors.initials: J
authors.lastname: Vaquero
authors.forename: Ana
authors.initials: A
authors.lastname: Hernando
authors.forename: Evelyn
authors.initials: E
authors.lastname: Galindo
authors.forename: Cristina
authors.initials: C
authors.lastname: Ripoll
authors.forename: Marta
authors.initials: M
authors.lastname: Puerto
authors.forename: Magdalena
authors.initials: M
authors.lastname: Salcedo
authors.forename: Rubén
authors.initials: R
authors.lastname: Francés
authors.forename: Ana
authors.initials: A
authors.lastname: Matilla
authors.forename: María V
authors.initials: MV
authors.lastname: Catalina
authors.forename: Gerardo
authors.initials: G
authors.lastname: Clemente
authors.forename: José
authors.initials: J
authors.lastname: Such
authors.forename: Rafael
authors.initials: R
authors.lastname: Bañares
mesh_terms: D000209:Acute-Phase Proteins; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001201:Ascites / Q000503:physiopathology*; D001483:Base Sequence; D002352:Carrier Proteins / Q000097:blood; D016207:Cytokines / Q000097:blood; D017931:DNA Primers / Q000235:genetics; D004269:DNA, Bacterial / Q000097:blood / Q000235:genetics; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008103:Liver Cirrhosis / Q000503:physiopathology*; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D008969:Molecular Sequence Data; D019936:Probiotics / Q000008:administration & dosage / Q000494:pharmacology*; D011446:Prospective Studies; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA; D012964:Sodium / Q000097:blood; D013030:Spain; D018709:Statistics, Nonparametric; D014655:Vascular Resistance / Q000187:drug effects; D014690:Venous Pressure / Q000187:drug effects; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D016207:Cytokines; D017931:DNA Primers; D004269:DNA, Bacterial; D008562:Membrane Glycoproteins; D012336:RNA, Ribosomal, 16S; D012964:Sodium; D000099231:Lipopolysaccharide-Binding Protein
keywords: bacterial translocation; cirrhosis; hyperdynamic circulation; portal hypertension; probiotic