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To examine current knowledge regarding the role of prebiotics in critical illness when administered singly or in combinations with probiotics (synbiotics).Recent experimental and clinical studies support the fact that bioecological intestinal control with early enteral nutrition enriched with synbiotics may reduce systemic inflammation, improve the immunological status of the intestinal mucosa and help prevent infections in critically ill patients. Three prebiotics, oligofructose, galactooligosaccharides and lactulose are able to modify the balance of intestinal microbiota. It appears that treatment with synbiotics during critical illness should restore the balance of microbial communities in a beneficial way with positive effects on intestinal permeability and bacterial translocation. Only data from small trials are currently available to support use of prebiotics and synbiotics in the treatment of different clinical scenarios. However, in some critical conditions, this supplementation has so far not been effective.Numerous questions about the molecular mechanisms of action or clinical indications of prebiotics remain unanswered. Large, randomized, multicentre trials are necessary to precisely define the role of prebiotics as therapeutic agents in critical illness. These trials must identify clinically significant improvements in relevant clinical endpoints before any large-scale usage is advocated for critical illness.