Role of probiotic supplementation in preventing ventilator-associated pneumonia among critically ill patients-a critical umbrella review of meta-analyses of randomized controlled trials.

Background: In critically ill patients, gut microbiome balance is often disrupted by antibiotics and disease-related stress. Probiotics may strengthen gut barrier function and lower the risk of ventilator-associated pneumonia (VAP), but their effectiveness in mechanically ventilated patients remains unclear. This umbrella review synthesizes evidence from systematic reviews on the association between probiotic therapy and VAP incidence. Methods: A comprehensive search was conducted in PubMed, Embase, Web of Science, the Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNKI) for systematic reviews published from database inception to July 20, 2025. Data were extracted using a standardized form that had been pilot-tested prior to use. Data were synthesized using both narrative and quantitative approaches. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (registration ID: CRD420251034247). Results: This umbrella review included 24 meta-analyses of randomized controlled trials (RCTs) involving 92,711 mechanically ventilated critically ill patients. Using a measurement tool to assess systematic reviews, version 2 (AMSTAR 2) tool, the methodological quality varied-a total of 4 were rated critically low, 12 were rated low, 1 was rated moderate, and 9 were rated high. Probiotic supplementation was associated with a reduced risk of VAP [odds ratio (OR) = 0.67, 95% confidence interval (CI): 0.61-0.75; relative risk (RR) = 0.74, 95% CI: 0.69-0.80] and nosocomial infections (OR = 0.81, 95% CI: 0.73-0.90; RR = 0.84, 95% CI: 0.80-0.88). Probiotics showed modest reductions in intensive care unit (ICU) stay [weighted mean difference (WMD) = -1.30 days, 95% CI: -1.59 to-1.02], overall hospital stay (WMD = -1.29 days, 95% CI: -1.79 to -0.79), duration of mechanical ventilation (WMD = -1.64 days, 95% CI: -2.07 to -1.22), and antibiotic use (WMD = -1.26 days, 95% CI: -2.25 to -0.28). The risk of diarrhea decreased based on OR estimates (OR = 0.77, 95% CI: 0.67-0.88), whereas RR estimates did not show a statistically significant difference (RR = 0.98, 95% CI: 0.94-1.01). Probiotic use was associated with a statistically significant reduction in ICU mortality (OR = 0.86, 95% CI: 0.79-0.94; RR = 0.94, 95% CI: 0.90-0.98), whereas hospital mortality was reduced only in RR analyses (RR = 0.92, 95% CI: 0.88-0.97) and not in OR Analyses (OR = 0.92, 95% CI: 0.84-1.01). Conclusion: Probiotics may offer potential benefits for mechanically ventilated, critically ill patients by reducing infections and improving certain clinical outcomes; however, the overall quality of the available evidence remains insufficient to support definitive conclusions. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251034247, CRD420251034247.