Effect of probiotic treatment on deranged neutrophil function and cytokine responses in patients with compensated alcoholic cirrhosis

Background/Aims: 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. (c) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.