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

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.

Anticandidal Activities by Lactobacillus Species: An Update on Mechanisms of Action

“…Clinical trials also confirm the immunomodulatory properties of lactobacilli in humans. Macnaughtan et al showed that L. casei -treated human patients with cirrhosis had lower plasma MIP-1B concentrations in an 8-week course; IL-1B and MPC-1 –in the alcoholic patient subgroup- and IL-17 –in the non-alcoholic cohort- plasma concentrations were also reduced [ 148 ]. Another clinical study reported that an L. reuteri -antibiotic combined therapy reduced abdominal pain and inflammatory markers (C-reactive protein levels) in acute uncomplicated diverticulitis patients; while also lowering hospitalization time [ 67 ].…”

Biomarkers of extracellular matrix formation are associated with acute-on-chronic liver failure

“…The SC cohort consisted of patients under follow-up in the outpatient clinic with a clinical, histological, or radiological diagnosis of liver cirrhosis (Child-Pugh score < − 10). 13 The study was approved by the joint University College London (UCL)/UCL Hospitals (UCLH) Committees (http://www.isrctn.com/ ISRCTN62619436), and written informed consent was obtained from each patient included in the study (Fig. 1).…”

From intestinal dysbiosis to alcohol-associated liver disease

“…[37][38][39] However, the major drawback of routine antibiotic prophylaxis is the emergence of multidrug-resistant organisms. 34 Thus, novel therapies have been proposed based on their ability to modify the altered intestinal microbiota such as probiotics and prebiotics, 19,[40][41][42][43][44][45] fecal microbiota transplantation, 46,47 phage therapy, 31 among others. Evidence for their use in clinical practice is limited and all require further studies.…”