A Double-Blind, Randomized Placebo-Controlled Trial of Probiotic Lactobacillus casei Shirota in Stable Cirrhotic Patients

Nutrients. 2020 Jun 2;12(6):1651. doi: 10.3390/nu12061651.

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.

Keywords: cirrhosis; cytokine; neutrophil; probiotic.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Chemokine CCL2 / blood
  • Chemokine CCL4 / blood
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Gastrointestinal Microbiome
  • Humans
  • Inflammation
  • Interleukin-17 / blood
  • Interleukin-1beta / blood
  • Lacticaseibacillus casei*
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / immunology
  • Liver Cirrhosis / microbiology
  • Liver Cirrhosis / therapy*
  • Male
  • Middle Aged
  • Neutrophils / immunology
  • Probiotics / administration & dosage*
  • Young Adult

Substances

  • CCL2 protein, human
  • Chemokine CCL2
  • Chemokine CCL4
  • IL17A protein, human
  • Interleukin-17
  • Interleukin-1beta

Grants and funding