Efficacy of probiotics or synbiotics for critically ill adult patients: a systematic review and meta-analysis of randomized controlled trials

Abstract

Background: Microbial dysbiosis in critically ill patients is a leading cause of mortality and septic complications. Probiotics and synbiotics have emerged as novel therapy on gut microbiota to prevent septic complications. However, current evidence on their effects is conflicting. This work aims to systematically review the impact of probiotics or synbiotics in critically ill adult patients.

Methods: A comprehensive search of the PubMed, CBM, Embase, CENTRAL, ISI, and CNKI databases was performed to identify randomized controlled trials that evaluate probiotics or synbiotics in critically ill patients. The quality assessment was based on the modified Jadad's score scale and the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1. The major outcome measure was mortality. Secondary outcomes included incidence of septic complications, sepsis incidence, length of intensive care unit (ICU) stay, incidence of non-septic complication, and ventilator day. Data synthesis was conduct by Review Manager 5.4.

Results: A total of 25 randomized controlled trials reporting on 5049 critically ill patients were included. In the intervention group, 2520 participants received probiotics or synbiotics, whereas 2529 participants received standard care or placebo. Pooling data from randomized controlled trials demonstrated a significant reduction in the incidence of ventilator-associated pneumonia (VAP) in the treatment group [(risk ratio (RR) 0.86; 95% confidence interval (CI): 0.78-0.95; p < 0.003, I² = 85%)]. However, in the subgroup analysis, the reduction of incidence of VAP was only significant in patients receiving synbiotics (RR = 0.61, 95% CI: 0.47-0.80, p = 0.0004, I² = 40%) and not significant in those receiving only probiotics (RR = 0.91, 95% CI: 0.82-1.01, p = 0.07, I² = 65%). Moreover, sepsis incidence of critically ill patients was only significantly reduced by the addition of synbiotics (RR = 0.41; 95% CI: 0.22-0.72, p = 0.005, I² = 0%). The incidence of ICU-acquired infections was significantly reduced by the synbiotics therapy (RR = 0.72; 95% CI: 0.58-0.89, p = 0.0007, I² = 79%). There was no significant difference in mortality, diarrhea, or length of ICU stay between the treatment and control groups.

Conclusions: Synbiotics is an effective and safe nutrition therapy in reducing septic complications in critically ill patients. However, in such patients, administration of probiotics alone compared with placebo resulted in no difference in the septic complications.

Keywords: Critically ill patients; Meta-analysis; Mortality; Probiotics; Synbiotics; Systematic review; Ventilator-associated pneumonia.

Figure 1.

PRISMA diagram detailing the literature search and the study selection/exclusion process. PRISMA Preferred Reporting Items for Systematic Reviews and Meta-analyses, RCT randomized controlled trials

Figure 2.

Forest plot of pooled weighted mean difference from RCTs evaluating the effect on risk ratio for mortality with probiotics and synbiotics therapy. RCTs randomized controlled trials, CI confidence intervals

Figure 3.

Forest plot of randomized controlled trials evaluating the efficacy for reducing the incidence of VAP. VAP ventilator-associated pneumonia, CI confidence intervals

Figure 4.

Forest plot of pooled data form RCTs demonstrating the reduction in risk of ICU-acquired infections. RCTs randomized controlled trials, CI confidence intervals, ICUs intensive care units

Figure 5.

Forest plot of pooled data form RCTs demonstrating the reduction in risk of sepsis. RCTs randomized controlled trials, CI confidence intervals

Figure 6.

Forest plot of pooled weighted mean difference from RCTs evaluating the risk ratio for length of ICU stay. RCTs randomized controlled trials, CI confidence intervals, ICUs intensive care units

Figure 7.

Effect on the incidence of diarrhea with probiotics or synbiotics therapy. CI confidence intervals

Figure 8.

Subgroup analysis: effects of different bacterial species on incidence of VAP. VSL#3 is a specific mixture of different bacterial species, consisting of four strains of Lactobacillus, three strains of Bifidobacterium and Streptococcus salivarius subsp. CI confidence intervals, VAP ventilator-associated pneumonia

Figure 9.

Funnel plot of included randomized controlled trials. RR risk ratio, SE standard error

Figure 10.

Risk of bias assessment for the randomized controlled trials (RCTs) included