Effect of probiotic treatment on deranged neutrophil function and cytokine responses in patients with compensated alcoholic cirrhosis.
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.
Stadlbauer
Vanessa
V
Liver Failure Group, The Institute of Hepatology, Division of Medicine, University College London, 69-75 Chenies Mews, London WC1E 6HX, UK.
Mookerjee
Rajeshwar P
RP
Hodges
Stephen
S
Wright
Gavin A K
GA
Davies
Nathan A
NA
Jalan
Rajiv
R
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
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