Successful treatment with fecal microbiota transplantation in patients with multiple organ dysfunction syndrome and diarrhea following severe sepsis

Abstract

BackgroundThe dysbiosis of intestinal microbiota plays an important role in the development of gut-derived infections, making it a potential therapeutic target against multiple organ dysfunction syndrome (MODS) after sepsis. However, the effectiveness of fecal microbiota transplantation (FMT) in treating this disease has been rarely investigated.MethodsTwo male patients, a 65-year-old and an 84-year-old, were initially diagnosed with cerebellar hemorrhage and cerebral infarction, respectively, after admission. During the course of hospitalization, both patients developed MODS, septic shock, and severe watery diarrhea. Demographic and clinical data were collected. Intestinal dysbiosis was confirmed by 16S rDNA-based molecular analysis of microbiota composition in fecal samples from the two patients. The two patients each received a single nasogastric infusion of sterile-filtered, pathogen-free feces from a healthy donor. Fecal samples were collected every two days post infusion to monitor changes in microbiota composition in response to treatment.ResultsFollowing FMT, MODS and severe diarrhea were alleviated in both patients. Their stool output and body temperature markedly declined and normalized. Significant modification of microbiota composition, characterized by a profound increase of commensals in the Firmicutes phylum and depletion of opportunistic organisms in the Proteobacteria phylum, was observed in both patients. Furthermore, we identified a reconstituted bacterial community enriched in Firmicutes and depleted of Proteobacteria that was associated with a decrease in the patients’ fecal output and in the levels of plasma inflammation markers.ConclusionsThe outcome of treating two patients with FMT indicates that restoration of the intestinal microbiota barrier can alleviate the infection and modulate the immune response. These findings warrant further investigation of FMT as a putative new therapy for treating microbiota-related diseases such as MODS.

The intestinal microenvironment in sepsis

“…In order for a fecal microbiota transplant to be successful, however, patients cannot receive antibiotics, as continued antimicrobial therapy would be expected to immediately alter the transplanted microbiome. This has limited the usage of fecal microbiota transplant in the intensive care unit to a few case reports in patients with intractable diarrhea (105;106). Determining the role of fecal microbiota transplant in critically ill patients thus represents an experimental strategy in sepsis, which will require rigorous studies to determine what role this could play in future treatment.…”

New insights into the gut as the driver of critical illness and organ failure

“…FMT has been proven to be highly successful in the setting of recurrent Clostridium difficle colitis (33;34). In addition, FMT has been successful in case reports of critically ill patients with dysbiosis-induced diarrhea not caused by Clostridium difficle (35;36). However, the utility of FMT in critically ill patients has practical limits posed by the need to avoid antibiotic usage, as giving antimicrobial agents to a patient would be expected to immediately alter the transplanted microbiome.…”

Glucocorticoid resistance as a major drive in sepsis pathology

“…For example, anti-TNF has proven somewhat protective in the most severe cases of sepsis [73,74] and treatment with recombinant interleukin-1 receptor was associated with significant improvement in sepsis patients with features of macrophage activation syndrome [75]. Third, sepsis may be much more than an inflammatory disease and issues such as clotting [76], complement activation [77,78] but also thermoregulation [79,80], metabolism [81][82][83][84], microbiome changes [85,86] and even circadian rhythm [87] disturbances may be equally important as inflammation. Fourth, many of the failed clinical trials have been based on pre-clinical work with small model organisms, such as mice.…”