Elsevier

Nutrition

Volume 59, March 2019, Pages 29-36
Nutrition

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

https://doi.org/10.1016/j.nut.2018.07.017Get rights and content

Highlights

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    Commensal microorganisms play vital roles in human physiology in nutrition, vitamin synthesis, drug metabolism, protection against infection, and recovery from illness.

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    Data from our ongoing intensive care unit (ICU) microbiome research revealed a rapid and marked change from a “healthy” microbiome to disrupted microbiota (dysbiosis) in ICU and surgical patients. The loss of “health-promoting” bacteria and overgrowth of pathogenic bacteria (dysbiosis) in the ICU is believed to contribute to nosocomial infections, sepsis, and organ failure.

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    A wide range of experimental studies have demonstrated that probiotics and synbiotics (probiotic and prebiotic combinations) may provide clinical benefit by maintaining gut epithelial barrier, increasing generation of nutritional substrate for host epithelial cells, changing the host metabolic transcriptional landscape, and optimizing immune system function.

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    Probiotics and synbiotics show promise in reducing community infections, sepsis, ICU infections, and Clostridium difficile colitis; however larger, targeted trials are needed to define how and who to best implement “dybiosis-therapy” with probiotics and synbiotics.

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    Future probiotic and symbiotic studies using microbiome signatures to characterize actual ICU and patient illness-related dysbiosis and to determine, and perhaps even to personalize, ideal probiotic and symbiotic therapies are needed.

Abstract

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.

Section snippets

Is our current approach to infection in the ICU and illness working?

A great deal of effort is spent in eradicating bacteria and other microbial, fungal, and viral species in the ICU. Data from the US Centers for Disease Control and Prevention show that 55% of all hospitalized patients receive an antibiotic during their stay, and in the ICU, this number rises to ∼70%. This observation has been confirmed by recent multinational ICU survey data from >14 000 patients in >1200 ICUs, finding 51% of patients were considered to be infected on day of survey and a

The evolving role for probiotics and synbiotics to promote recovery in the ICU

Is it possible that to improve critical care outcomes we should be giving “friendly” bacteria to ICU patients, rather than eradicating them? Perhaps our success as a species is based on the evolved presence of the trillions of bacterial symbionts that each of us live in harmony with each day? This raises the key question of whether we should be shifting our focus to treating dysbiosis by restoring a normal, healthy microbiome in ICU patients in order to fight infection and improve ICU recovery.

Mechanistic role of probiotics and synbiotics in critical care

Mice that receive fecal transplants (microbial communities) from obese or malnourished humans phenocopy the disease associated with the transplant, indicating that abnormal microbial communities drive nutritionally related diseases [15], [16]. Similarly, the microbiota are linked to immune-mediated inflammatory diseases like rheumatoid arthritis and multiple sclerosis and inflammatory bowel diseases (IBD) like ulcerative colitis and Crohn's disease [17]. Although the microbiota can induce

Maintaining epithelial barrier function

The intestinal epithelium is comprised of a single layer of columnar epithelial cells that detect and respond to dietary nutrients and molecular cues within the environment. Enterocytes comprise the largest cell population in the small intestinal epithelia and these harvest dietary nutrients from the lumen to maintain energy homeostasis for all animals. Secretory cells, like goblet and Paneth cells, secrete proteins into the luminal environment to protect the epithelia from the harmful microbes

Review of current data for probiotic/synbiotic use in critical illness

Probiotic use in critical care has been the subject of an increasing number of clinical trials and meta-analysis focused on a range of outcomes after critical illness. Many clinical trials and meta-analysis efforts have focused on the role of probiotics in reducing ventilator-associated pneumonia (VAP). Despite promising data for probiotic use in reducing overall infections, the role of probiotics as a strategy to prevent VAP has been controversial. Recently, a Cochrane review of probiotic

Concluding remarks: defining the ICU microbiome (dysbiosis) to target probiotic therapy

Characterization of ICU microbiome changes may provide key insight to guide development of diagnostic and therapeutic interventions with probiotics and synbiotics using microbiome signatures. Our research group recently completed a multicenter trial to characterize the effect critical illness on the microbiome [20]. The ICU Microbiome Trial assessed fecal and oral samples of 115 adult medical and surgical ICU patients, processed according to standardized Earth Microbiome Project protocols. We

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    • Cited by (0)

    P.E.W. received funding for a research grant in prebiotic therapy in critical illness from Abbott Inc. J.M.D. received funding for experimental probiotic research from the American Society for Parenteral and Enteral Nutrition Rhoads Research Foundation.

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