Synbiotic-associated improvement in liver function in cirrhotic patients: Relation to changes in circulating cytokine messenger RNA and protein levels

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Abstract
Background/Aims: Mechanisms by which synbiotic treatment improves liver function in patients with cirrhosis are unknown. This study was performed to address this important issue. Patients and methods: Thirty cirrhotic patients were randomized to receive synbiotic or placebo preparations for 7 days. Viable faecal counts of Lactobacillus species, Child-Pugh class, plasma retention rate of indocyanine green (ICGR15), whole blood tumour necrosis factor alpha (TNF-α) mRNA and interleukin-6 (IL-6) mRNA, serum TNF-α, soluble TNF receptor (sTNFR)I, sTNFRII and IL-6 and plasma endotoxin levels were measured pre- and post-treatment. Results: Synbiotic treatment was associated with significantly increased faecal lactobacilli counts and significant improvements in ICGR15 and Child-Pugh class. Significant increases in whole blood TNF-α mRNA and IL-6 mRNA, along with serum levels of sTNFRI and sTNFRII, also occurred. TNF-α and IL-6 levels correlated significantly, both at baseline and post-synbiotic treatment. Synbiotic-related improvement in ICGR15 was significantly associated with changes in IL-6, both at mRNA and protein levels, and unrelated to plasma endotoxin values. No significant changes in any study parameter followed placebo treatment. Conclusions: Short-term synbiotic treatment proven to modulate gut flora significantly improves liver function in patients with cirrhosis. Benefit is unrelated to reduction in endotoxaemia and may be mediated, at least in part, by treatment-related induction of IL-6 synthesis by TNF-α.

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