Prebiotics, probiotics, and synbiotics therapy in critically ill patients: a systematic review and network meta-analysis.

Abstract

Background: Critically ill patients frequently develop intestinal dysbiosis, leading to gastrointestinal (GI) symptoms and infectious complications. No network meta-analysis (NMA) has compared the relative effectiveness of prebiotics, probiotics, and synbiotics for reducing the risk of GI symptoms in critically ill patients.

Objective: This study aimed to evaluate their comparative effects in preventing GI symptoms and improving clinical outcomes.

Methods: MEDLINE, CENTRAL, and Web of Science were searched through June 2025. Eligible randomized controlled trials enrolled critically ill adults and compared prebiotics, probiotics, or synbiotics with controls (placebo or usual care). The primary outcome was GI symptom incidence. Secondary outcomes included mortality, intensive care unit (ICU) length of stay, mechanical ventilation duration, infectious complications, and adverse events. A frequentist random-effects NMA was conducted. Treatment rankings were exploratory, and certainty of evidence was not formally assessed.

Results: Thirty-three randomized controlled trials involving 5,073 patients were included in the analysis of GI symptoms. Compared with control, synbiotics significantly reduced the risk of GI symptoms (risk ratio [RR] 0.52; 95% confidence interval [CI]: 0.35 to 0.77), as did prebiotics (RR 0.66; 95% CI: 0.49 to 0.87). Probiotics produced a similar directional effect, but the difference was not statistically significant (RR 0.81; 95% CI: 0.60 to 1.10). No significant differences were found between the active interventions. Subgroup analyses suggested differences according to the ICU population. Among medical intensive care patients, prebiotics were associated with a lower risk of GI symptoms than control, whereas probiotics and synbiotics were associated with a lower risk among surgical intensive care patients.

Conclusions: Synbiotics and prebiotics were associated with a significantly lower risk of gastrointestinal symptoms in critically ill patients, whereas probiotics showed a similar but statistically nonsignificant effect. No active intervention was significantly superior to another. The findings suggest that the relative benefits of these interventions may differ between medical and surgical intensive care populations. Nevertheless, the results should be interpreted cautiously because certainty of evidence was not formally assessed.PROSPERO registration number: CRD420251015729; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251015729.