ABSTRACT & COMMENTARY
Probiotics and Their Immunological Impact on Liver Cirrhosis Findings from a double-blind, randomized, placebo-controlled trial REFERENCE
Macnaughtan J, Figorilli F, García-López E, et al. A double-blind, randomized placebo-controlled trial of probiotic Lactobacillus casei Shirota in stable cirrhotic patients. Nutrients. 2020;12(6):1651. STUDY OBJECTIVE
To ascertain if probiotic Lactobacillus casei Shirota (LcS) positively impacts neutrophil function and rates of infection in patients with liver cirrhosis versus a placebo. DESIGN
A double-blind, randomized and placebocontrolled trial at 2 hospitals in the United Kingdom PARTICIPANTS
Investigators screened 110 patients and included 92 with cirrhosis of any etiology at 2 hospitals. These patients presented with relevant clinical findings consistent with a cirrhosis diagnosis as well as a Child-Pugh score less than 10. Patients were between ages 18 and 78 years and had abstained from alcohol consumption for 2 weeks preceding screening. They were randomly assigned (1:1) to either the intervention or placebo group being stratified for alcoholic and nonalcoholic cirrhosis etiology. Exclusion criteria included: • Child-Pugh score >10 • Active infection • Antibiotic treatment 7 days prior to enrollment • Gastrointestinal hemorrhage • Use of immunomodulating agents • Use of proton pump inhibitors • Use of pre-, pro-, or synbiotics • Creatinine >150 mmol/L • Hepatic encephalopathy II-IV • Pancreatitis • Organ failure • Hepatic malignancy • Pregnancy
STUDY PARAMETERS ASSESSED
Patients in the intervention group received a 65-mL bottle of a LcS drink that yielded a 6.5 billion colony-forming-unit (CFU) bacteria (Yakult Europe) content, to be taken 3 times per day for 6 months. The placebo group was given a similar-looking and similar-tasting drink yielding no bacteria. Patients received 45 bottles every 2 weeks, with the empty, consumed bottles being a measure of compliance. Investigators recorded clinical benchmarks inclusive of blood and biochemical testing at screening, days 0 and 14, and months 1, 3, and 6. They gathered analytes relevant to intestinal hyperpermeability at months 0, 1, and 6. PRIMARY OUTCOME MEASURES
One of the primary endpoints in this study was the change in neutrophil function. Investigators evaluated this using isolation and coincubation methods to measure reactive oxygen species (ROS) production and prevalence of phagocytosis. The additional primary endpoint included incidence of infection, evaluated through routine clinical blood chemistry. Secondary outcomes included plasma cytokine profile concentration at various intervals, concluding at 6 months. Investigators evaluated intestinal hyperpermeability using urinary lactulose rhamnose ratio, venous endotoxin concentrations, and bacterial DNA identification with polymerase chain reaction (PCR) testing. The final secondary outcome was the quality-of-life assessment, which was accomplished with the use of the standardized SF-36 tool.
28 ©2021 NATURAL MEDICINE JOURNAL. ALL RIGHTS RESERVED. NMJ, MAY 2021 SUPPLEMENT—VOL. 13, NO. 51 (SUPPL)
By Ramneek Bhogal, DC, DABCI KEY FINDINGS
Overall, no significant differences in neutrophil function were observed between the intervention and placebo groups. For patients with atypical neutrophil function at the study’s onset, the 6-month LcS treatment yielded a significantly higher ROS production outcome compared to the placebo arm [1403(1214– 1821) versus 1168.00(1014–1266), P=0.02]. This is suggestive of improved neutrophil function in that subset. No significant changes in infection episodes were noted between randomized groups at the end of the study. Intestinal hyperpermeability was also observed to be in a normal range in both groups, with bacterial DNA positivity being 10.1% (placebo group) and 8.1% (LcS group). Outcomes with plasma cytokine concentrations were not significantly different in the vast majority of specific cytokines evaluated in the study. It was observed that LcS lowered median plasma interleukin 1 beta (IL1B; P=0.04) and monocyte chemotactic protein-1(MCP-1; P=0.04) concentration in the alcoholic subset. Further observation revealed a lowered interleukin 17A (IL17A) concentration in the nonalcoholic cohort (P=0.02). Macrophage inflammatory protein-1 beta (MIP-1β) concentrations were lowered in the LcS as a whole at the 6-month interval (P=0.04). The 36-Item Short Form Health Survey (SF-36) scores assessing quality of life showed no significant differences between either arm of the study.
