Probiotic and synbiotic therapy in the critically ill: State of the art.

Recent medical history has largely viewed our bacterial symbionts as pathogens to be eradicated rather than as essential partners in optimal health. However, one of the most exciting scientific advances in recent years has been the realization that commensal microorganisms (our microbiome) play vital roles in human physiology in nutrition, vitamin synthesis, drug metabolism, protection against infection, and recovery from illness. Recent data show that loss of "health-promoting" microbes and overgrowth of pathogenic bacteria (dysbiosis) in patients in the intensive care unit (ICU) appears to contribute to nosocomial infections, sepsis, and poor outcomes. Dysbiosis results from many factors, including ubiquitous antibiotic use and altered nutrition delivery in illness. Despite modern antibiotic therapy, infections and mortality from often multidrug-resistant organisms are increasing. This raises the question of whether restoration of a healthy microbiome via probiotics or synbiotics (probiotic and prebiotic combinations) to intervene on ubiquitous ICU dysbiosis would be an optimal intervention in critical illness to prevent infection and to improve recovery. This review will discuss recent innovative experimental data illuminating mechanistic pathways by which probiotics and synbiotics may provide clinical benefit. Furthermore, a review of recent clinical data demonstrating that probiotics and synbiotics can reduce complications in ICU and other populations will be undertaken. Overall, growing data for probiotic and symbiotic therapy reveal a need for definitive clinical trials of these therapies, as recently performed in healthy neonates. Future studies should target administration of probiotics and synbiotics with known mechanistic benefits to improve patient outcomes. Optimally, future probiotic and symbiotic studies will be conducted using microbiome signatures to characterize actual ICU dysbiosis and determine, and perhaps even personalize, ideal probiotic and symbiotic therapies.