title: Effect of probiotic treatment on deranged neutrophil function and cytokine responses in patients with compensated alcoholic cirrhosis.
abstract: OBJECTIVE
  Endotoxaemia contributes to neutrophil dysfunction, infection risk and mortality in patients with alcoholic cirrhosis. As probiotics may decrease Gram-negative gut organisms, we hypothesised that probiotic treatment would restore neutrophil function.
  
  
  METHODS
  In an open-label study, patients with alcoholic cirrhosis (n=12) received Lactobacillus casei Shirota (6.5 x 10(9)) 3 times daily for 4 weeks. Data were compared to healthy controls (n=13) and cirrhotic patients (n=8) who did not receive probiotics. Neutrophil oxidative burst, phagocytosis, toll-like-receptor (TLR) expression, plasma cytokines and ex vivo endotoxin-stimulated cytokine production were measured.
  
  
  RESULTS
  Baseline neutrophil phagocytic capacity in patients was significantly lower compared to healthy controls (73% versus 98%, p<0.05), but normalised at the end of the study (n=10, 100%, p<0.05). No improvement was seen in disease controls. Soluble TNF-receptor (sTNFR)-1 and-2 and interleukin (IL)10 were significantly elevated in patients' plasma but did not change during the study. Ex vivo endotoxin-stimulated levels of sTNFR1, sTNFR2 and IL10 were significantly lower at the end of the study (p<0.05). TLR2, 4 and 9 were overexpressed in patients. TLR4 expression normalised by the end of the study.
  
  
  CONCLUSIONS
  Our data provide a proof-of-concept that probiotics restore neutrophil phagocytic capacity in cirrhosis, possibly by changing IL10 secretion and TLR4 expression, warranting larger randomised controlled and mechanistic studies.
authors.affiliation: Liver Failure Group, The Institute of Hepatology, Division of Medicine, University College London, 69-75 Chenies Mews, London WC1E 6HX, UK.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Stadlbauer
authors.forename: Rajeshwar P
authors.initials: RP
authors.lastname: Mookerjee
authors.forename: Stephen
authors.initials: S
authors.lastname: Hodges
authors.forename: Gavin A K
authors.initials: GA
authors.lastname: Wright
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Davies
authors.forename: Rajiv
authors.initials: R
authors.lastname: Jalan
mesh_terms: D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D007780:Lacticaseibacillus casei / Q000502:physiology; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects; D019936:Probiotics / Q000494:pharmacology / Q000627:therapeutic use*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood*; D016897:Respiratory Burst / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000097:blood; D051197:Toll-Like Receptor 4 / Q000097:blood; D051217:Toll-Like Receptor 9 / Q000097:blood
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D016753:Interleukin-10