Introduction

Critically ill patients are particularly susceptible to intestinal dysbiosis because of antibiotic exposure, intestinal ischemia, sedation, and catecholamine use [1,2], with consequences extending beyond the gastrointestinal tract and including impaired intestinal barrier function, bacterial translocation, systemic inflammation, and increased vulnerability to nosocomial infections [3,4]. Notably, gastrointestinal dysfunction affects up to 60% of intensive care unit (ICU) patients, and approximately 50% of those receiving enteral nutrition develop symptoms of feeding intolerance, including diarrhea, vomiting, and increased gastric residual volume [5]. These symptoms frequently necessitate interruption of enteral nutrition, resulting in suboptimal nutrient delivery and potentially worsening patient outcomes [6].

Therefore, gut microbiota-modulating "biotics" have attracted considerable attention. Prebiotics are substrates selectively utilized by host microorganisms to confer health benefits [7]. Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit to the host [8]. Moreover, synbiotics are mixtures of live microorganisms and substrates selectively utilized by host microorganisms that together confer a health benefit [9]. Collectively, when administered prophylactically, these interventions may help restore gut homeostasis, reduce the occurrence of gastrointestinal symptoms, prevent infectious complications, and potentially improve clinical outcomes in critically ill patients.

The Japanese Critical Care Nutrition Guideline 2024 (JCCNG 2024) strongly recommends prebiotics (GRADE 1B) and synbiotics (GRADE 1C), whereas probiotics are conditionally recommended (GRADE 2C) [10]. Although no difference in in-hospital mortality was observed, the guidelines reported differences in adverse events, including diarrhea. Previous network meta-analyses have assessed the effects of biotic interventions on ventilator-associated pneumonia (VAP) and nosocomial infections in critically ill patients. Nonetheless, none have systematically compared the efficacy of prebiotics, probiotics, and synbiotics regarding gastrointestinal symptoms [11,12]. Furthermore, gastrointestinal symptoms are clinically important outcomes because they directly reflect gut function, serve as the most proximal indicator of microbiome modulation, and substantially influence nutritional adequacy and patient comfort in the ICU [13,14].

Although several studies have evaluated prebiotics, probiotics, and synbiotics simultaneously [11,12], no studies have assessed gastrointestinal symptoms as an outcome in critically ill patients. As determining which biotic intervention is most effective in reducing the incidence of gastrointestinal symptoms in critically ill patients is clinically important, this study aimed to systematically identify randomized controlled trials evaluating biotics in critically ill patients and to compare the relative efficacy of each biotic group in preventing gastrointestinal symptoms using a network meta-analysis.