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Stadlbauer et al (2008) Effect of probiotic treatment on deranged neutrophil function and cytokine responses in patients with compensated alcoholic cirrhosis

Stadlbauer et al (2008) Effect of probiotic treatment on deranged neutrophil function and cytokine responses in patients with compensated alcoholic cirrhosis

Citation

Stadlbauer V, Mookerjee RP, Hodges SJ, Wright G, Davies NA, Jalan R (2008) Effect of probiotic treatment on deranged neutrophil function and cytokine responses in patients with compensated alcoholic cirrhosis. Journal of Hepatology 48(6): 945-951.

Objective

To determine:

  • whether the neutrophil function in patients with well-compensated alcoholic cirrhosis is defective.
  •  If so, to determine whether consumption of Lactobacillus casei Shirota (LcS) restores the neutrophil defect.

Methods

In this proof of concept, open-label study lasting four weeks, 12 patients consumed LcS (6.5 x 109) three times daily in the form of a fermented milk drink. The following parameters were measured at baseline and after four weeks: neutrophil oxidative burst, phagocytosis, toll-like receptor (TLR) expression, plasma cytokines and ex vivo endotoxin-stimulated cytokine production. Data were compared with 13 healthy controls and 8 similar patients who did not consume probiotics

Results

  • At the start of the study, the neutrophil phagocytic capacity in the patients was lower than the healthy controls (73% vs. 98%; P
  • Neutrophil phagocytic capacity became normalised after the four weeks of LcS intervention (n=10; 100%; P
  • Plasma levels of soluble TNF-receptor (sTNFR)-1 and -2, and IL-10 were significantly higher in patients compared to healthy controls; this did not change during the study.
  • Levels of sTNFR1, sTNFR1 and IL-10 (ex vivo and endotoxin-stimulated) were significantly lower after LcS intervention (P
  • TLR2, TLR4 and TLR9 were overexpressed in the patients; TLR4 expression became normalised after LcS intervention.
  • There were no adverse events and markers of inflammation and infection (e.g. white cell count and C-reactive protein) showed no change after the probiotic intervention.

[Explanatory note: Toll-like receptor (TLR)2 recognises peptidoglycan from Gram-positive bacteria; TLR 4 recognises lipopolysacccharide (endotoxin) from Gram-negative bacteria; TLR9 recognises certain motifs of bacterial DNA.]

Conclusions

These results provide proof of the concept that probiotics restore neutrophil phagocytic capacity in cirrhosis. It is hypothesised that the mechanism of activity may involve changing IL-10 secretion and TLR4 expression. Larger, randomised controlled trials are indicated.

 
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