Fecal microbiota transplantation for multiple organ dysfunction syndrome

Approximately 40 trillion bacteria reside inside the human intestine, meaning there are at least as many cells of microbial origin as human origin [1]. While it was once believed that bacteria and humans simply coexisted in the same space, a wide body of evidence now suggests that host–microbial communication is more complex than ever imagined and the microbiome plays a critical role in maintaining host homeostasis. The microbiome is also altered in multiple disease states, including heart disease [2], cancer [3], and Clostridium difficile infection [4], with changes detectable in microbial composition, number, diversity, and virulence compared to healthy controls. While the majority of studies linking the microbiome to disease are associative, there is increasing evidence that the microbiome plays a crucial role in mediating the pathophysiology of multiple acute and chronic illnesses. The gut has long been hypothesized to be “the motor” of multiple organ dysfunction syndrome (MODS) [5]. Notably, the microbiome is markedly altered in the intensive care unit (ICU). A recent study sampling stool from 115 critically ill patients revealed decreases in Firmicutes and Bacteroidetes—bacteria that are prevalent in the healthy intestine—with increases in opportunistic Proteobacteria [6]. Although these findings cannot determine whether an altered microbiome functions as a marker or mediator in the development of MODS, it raises the question as to whether altering microbial ecology and restoring diversity of the microbiome may be a novel therapeutic strategy in critical illness. Multiple methods to manipulate host bacteria have been tried in patients, ranging from giving exogenous bacteria in the form of probiotics to selecting out pathogenic microbes via selective decontamination of the digestive tract. While each of these strategies has shown some clinical promise [7, 8], debatably the most effective method of altering the microbiome in human disease is fecal microbial transplantation (FMT). FMT is a procedure where stool is collected from a healthy donor, filtered for particulate matter, and the liquid portion given to the patient via nasogastric tube or via the rectum [9]. FMT has been demonstrated to be significantly more effective in recurrent C. difficile infections than other available therapies [10]. Treatment failures still occur, however, which is not surprising given that we do not yet fully understand the mechanisms responsible for the success of FMT, nor do we know the optimal dose and timing required for a successful transplant. Notably, viruses, fungi, viable colonocytes, immunoglobulins, metabolites, and natural bacteriocins may be present in FMT and impact outcomes [11, 12]. The literature on FMT in critical care is limited to a single case report [11]. The barriers to utilizing FMT in the ICU are significant. The impact of giving bacteria to a patient with a markedly altered microbiome who likely has a component of immunosuppression is unknown and has inherent theoretical risks. In addition, the majority of critically ill patients receive antibiotics at some point during their ICU stay, and initiation or continuation of antibiotic therapy would be expected to markedly alter the microbiome following FMT. As such, there must be a commitment to stopping antibiotics both prior to and following FMT to allow the transplanted bacteria to take hold and remodel the microbiome. This is a difficult * Correspondence: [email protected] Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, GA, USA Emory University School of Medicine, 101 Woodruff Circle, Suite WMB 5105, Atlanta, GA 30322, USA