Abstract
Background: In cirrhosis, a pathological gut microbiome has been linked with immune dysfunction. A pilot study of probiotic Lactobacillus casei Shirota (LcS) in alcoholic cirrhosis demonstrated significant improvement in neutrophil function. This study aimed to evaluate the efficacy of LcS on neutrophil function and significant infection rates in patients with cirrhosis. Methods: 92 cirrhotic patients (Child–Pugh score ≤10) were randomized to receive LcS or placebo, three times daily for six months. Primary end-points were incidence of significant infection and neutrophil function. Secondary end-points were cytokine profile, endotoxin, bacterial DNA positivity, intestinal permeability and quality of life. Results: Rates of infection, decompensation or neutrophil function did not differ between placebo and probiotic groups. LcS significantly reduced plasma monocyte chemotactic protein-1 and, on subgroup analysis, plasma interleukin-1β (alcoholic cirrhosis), interleukin-17a and macrophage inflammatory protein-1β (non-alcoholic cirrhosis), compared with placebo. No significant differences in intestinal permeability, bacterial translocation or metabolomic profile were observed. Conclusion: LcS supplementation in patients with early cirrhosis is safe. Although no significant infections were observed in either group, LcS improved cytokine profile towards an anti-inflammatory phenotype, an effect which appears to be independent of bacterial translocation.
Highlights
Patients with cirrhosis exhibit a heightened susceptibility to infection [1]
Intestinal dysbiosis is pathophysiologically linked to all complications of cirrhosis and implicated in immune dysfunction, resulting in heightened susceptibility to infection [22]
A reduction in autochthonous bacterial populations in stool is typically observed in cirrhosis with reciprocal expansions in pathobionts, including proteobacteria [23]
Summary
Patients with cirrhosis exhibit a heightened susceptibility to infection [1]. The resultant systemic inflammatory response has been shown to predict poor outcome in acute decompensation and acute-on-chronic liver failure (ACLF). Neutrophil function has been shown to be disordered in cirrhosis, characterized by an increased resting burst and diminished neutrophil phagocytosis This is associated with increased risk of infection, organ failure and mortality. Ex vivo treatment of plasma from patients with anti-CD14 antibodies or with endotoxin removal columns prevented transference of susceptibility to normal neutrophils, implicating endotoxemia in pathogenesis. In keeping with this hypothesis, long-term intestinal decontamination with norfloxacin in cirrhotic patients reduces the incidence of infective episodes and complications [4]. This study aimed to evaluate the efficacy of LcS on neutrophil function and significant infection rates in patients with cirrhosis
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