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

Background/Aim

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 (6.5×10⁹) 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.

Abbreviations: TNFα, tumour necrosis factor alpha, sTNFR, soluble tumour necrosis factor alpha receptor, TLR, Toll-like receptor, IL, interleukin

Keywords: Alcoholic cirrhosis, Neutrophil function, Phagocytosis, Probiotic, Cytokine, Toll-like receptor