The effect of short term treatment with probiotic VSL#3 on various clinical and biochemical parameters in patients with liver cirrhosis.

The evidence is mounting that alterations of innate immunity and gut microbiota contribute to chronic liver disease and its complications. Modulation of intestinal microbiota is an emerging therapeutic strategy in hepatology. Probiotics through modulation of intestinal milieu have the potential to affect the course of liver disease. The data concerning the influence of probiotics on various plasma molecules and compounds involved in the pathogenesis of hyperdynamic circulatory state in liver cirrhosis is still not confluent and require further evaluation. In our study twenty patients with compensated and decompensated liver cirrhosis and ten healthy controls received probiotic VSL#3 daily for 28 days. Plasma levels of interleukin 6 (IL-6), vascular endothelial growth factor (VEGF), plasminogen activator inhibitor (PAI), macrophage inflammatory protein 3/α (MIP-3 α/CCL20), monocyte chemotactic protein-1α (MCP-1/CCL2), human myeloperoxidase (MPO), nitric oxide (NO), prostaglandins, thromboxane (TXB2) and big-endothelin were measured at baseline, day 14 and 28 of probiotic administration. The incidence of hepatic encephalopathy was assessed with critical flicker frequency. Changes in clinical, biochemical and microbiological parameters were evaluated. The stage of liver cirrhosis correlated with an increase in plasma levels of pro-inflammatory cytokines (IL-6) and chemotactic chemokines involved in immune cell trafficking (MIP-3α/CCL20). Probiotic administration in patients with liver cirrhosis led to modulation of plasma levels of several molecules and compounds measured (MIP-3α/CCL20, NO, big-endothelin, TXB2 and MPO). The grade of encephalopathy during the course of probiotic supplementation remained unaffected in both groups of patients. VSL#3 treatment was well tolerated and safe in patients with liver disease. In patients with compensated and decompensated liver cirrhosis, VSL#3 manipulates selected plasma molecules and compounds involved in hyperdynamic circulatory dysfunction. Short term VSL#3 administration affects several clinical and biochemical parameters commonly altered in liver cirrhosis.

Clinical analysis of systemic and adipose tissue levels of selected hormones/adipokines and stromal-derived factor-1.

Recent studies demonstrated that selected hormones/adipokines may be involved into the regulation of bone metabolism and bone marrow-derived hematopoietic stem/progenitor cells (HSPCs) mobilization in humans. Interestingly, in obese individuals significantly higher numbers of spontaneously circulating stem cells are also observed. Therefore in this study we comprehensively examined plasma and AT (subcutaneous and visceral/omental) levels of hormones/adipokines involved in HSPCs mobilization in lean, overweight and obese individuals as well as verified their potential associations with concentrations of HSPCs chemoattractant, stromal-derived factor-1 (SDF-1). Blood and AT samples (35 subcutaneous and 35 omental) were obtained from individuals undergoing elective surgery. Plasma and AT-derived interstitial fluid levels of resistin, visfatin, osteocalcin and SDF-1 were measured using ELISA. In our study obese patients had almost significantly (P<0.06) higher plasma visfatin and resistin levels as well as lower osteocalcin concentrations (P<0.04) than lean individuals. Osteocalcin and resistin concentrations were strongly associated with levels of SDF-1 and metalloproteinases (MMP 2 and 9). AT levels of all examined substances were significantly lower than the corresponding levels in the plasma (in all cases at least P<0.05), and depot-specific differences in the concentrations of these factors were found only in terms of osteocalcin and SDF-1. In addition, subcutaneous and visceral/omental concentrations of osteocalcin and visfatin, but not of resistin, were associated with values of such parameters as age, body mass or adiposity indexes (BMI and BAI, respectively) and/or waist-to-hip ratio (WHR). In summary, our study showed that in obese individuals the biochemical constellation of adipokines/hormones involved in the process of HSPCs mobilization resembles this observed during pharmacological HSPCs mobilization. Moreover, our study offers further indirect translational evidence for existence of a biochemical cross-talk between bone and AT metabolism (so called - bone-fat- axis) in humans.