Probiotic and synbiotic therapy in critical illness: a systematic review and meta-analysis

Abstract

BackgroundCritical illness is characterized by a loss of commensal flora and an overgrowth of potentially pathogenic bacteria, leading to a high susceptibility to nosocomial infections. Probiotics are living non-pathogenic microorganisms, which may protect the gut barrier, attenuate pathogen overgrowth, decrease bacterial translocation and prevent infection. The purpose of this updated systematic review is to evaluate the overall efficacy of probiotics and synbiotic mixtures on clinical outcomes in critical illness.MethodsComputerized databases from 1980 to 2016 were searched. Randomized controlled trials (RCT) evaluating clinical outcomes associated with probiotic therapy as a single strategy or in combination with prebiotic fiber (synbiotics). Overall number of new infections was the primary outcome; secondary outcomes included mortality, ICU and hospital length of stay (LOS), and diarrhea. Subgroup analyses were performed to elucidate the role of other key factors such as probiotic type and patient mortality risk on the effect of probiotics on outcomes.ResultsThirty trials that enrolled 2972 patients were identified for analysis. Probiotics were associated with a significant reduction in infections (risk ratio 0.80, 95 % confidence interval (CI) 0.68, 0.95, P = 0.009; heterogeneity I2 = 36 %, P = 0.09). Further, a significant reduction in the incidence of ventilator-associated pneumonia (VAP) was found (risk ratio 0.74, 95 % CI 0.61, 0. 90, P = 0.002; I2 = 19 %). No effect on mortality, LOS or diarrhea was observed. Subgroup analysis indicated that the greatest improvement in the outcome of infections was in critically ill patients receiving probiotics alone versus synbiotic mixtures, although limited synbiotic trial data currently exists.ConclusionProbiotics show promise in reducing infections, including VAP in critical illness. Currently, clinical heterogeneity and potential publication bias reduce strong clinical recommendations and indicate further high quality clinical trials are needed to conclusively prove these benefits.

Lactobacillus rhamnosus GG treatment improves intestinal permeability and modulates inflammatory response and homeostasis of spleen and colon in experimental model of Pseudomonas aeruginosa pneumonia

“…The effect of LGG on key gut barrier components, including reduced gut apoptosis, enhanced mucin barrier formation and Muc2 expression, and potential effects on tight junction proteins are all targets for future mechanistic explorations of the pathways responsible for the observed survival benefit of probiotics in pneumonia (21). Further, this data provides potential mechanistic explanations for existing clinical trial data showing probiotic therapy can reduce ventilator associated pneumonia (10, 12, 34) and perhaps specifically P. aeruginosa pneumonia (11) in critically ill patients.…”

“…Probiotic use in ICU has recently been supported by several clinical trials and meta-analysis work (10–12) showing significant reduction of infections, and specifically ventilator-associated pneumonia (VAP) (13). Although probiotics show promise as effective treatments in a range of clinical conditions, the specific mechanisms of benefit are complex and not fully described (14).…”

The intestinal microenvironment in sepsis

“…Recent meta-analyses on over 2000 patients demonstrate that probiotics reduce the rate of ventilator associated pneumonia and infections in critically ill patients without differences in mortality, hospital length of stay or length of mechanical ventilation (107). However, conclusions are limited by low quality evidence, heterogeneity of study design and outcome measures.…”

Forkhead Box Protein O1 is Linked to Anti-Inflammatory Probiotic Bacteria Acting through Nuclear Factor-κB Pathway

“…Although the mechanisms are well described in vitro and in animal models, the actual mechanism of action of probiotics in humans has not been clearly addressed [9]. Meta-analysis of human studies using probiotics interventions have generated contradictory results in part due to differences in study design (variety of probiotic strains, daily doses and length of administration) but also due to the poor understanding of the mechanisms by which these probiotics elicit their effects [10][11][12][13].…”