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

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,I^(2)=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,I^(2)=40%)and not significant in those receiving only probiotics(RR=0.91,95%CI:0.82-1.01,p=0.07,I^(2)=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,I^(2)=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,I^(2)=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.