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.
Highlights
The 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
It has been shown that fecal microbiota transplantation (FMT) can cure recurrent Clostridium difficile infection (CDI), which results from persistent disruption of commensal gut microbiota, by reestablishing the intestinal microbiota balance [5]
Consistent with the data obtained from the molecular phylogenetic tree, the OUT and principal component (PC) analyses (Fig. 1a and b) both showed that the structure of the microbiome was dramatically changed in both patients compared to that of the donor
Summary
The 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. The normal function of the gastrointestinal tract is important for immune defense against pathogens in the human body. It is well-acknowledged that gut microbiota may serve as a physical barrier that maintains mucosal integrity by preventing penetration of the epithelial barrier by pathogens and by modulating immunological activity [1]. Disruption of the gut microbiota barrier contributes to the development of many gastrointestinal diseases along with multiple extraintestinal diseases [2]. Fecal microbiota transplantation (FMT) has been proposed as a treatment for restoring the gut microbiota barrier [3, 4]. The nature of this restoration and whether a transition to an ecologically stable intestinal microbial population takes place during FMT treatment remains to be elucidated
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