Successful treatment of severe sepsis and diarrhea after vagotomy utilizing fecal microbiota transplantation: a case report

Abstract

Introduction: Dysbiosis of intestinal microbiota likely plays an important role in the development of gut-derived infections, making it a potential therapeutic target against sepsis. However, experience with fecal microbiota transplantation (FMT) in the treatment of sepsis and knowledge of the underlying mechanisms are extremely lacking. In this article, we describe a case of a patient who developed sepsis after a vagotomy and later received an infusion of donor feces microbiota, and we report our findings.

Methods: A 44-year-old woman developed septic shock and severe watery diarrhea 4 days after undergoing a vagotomy. Antibiotics, probiotics and supportive treatment strategies were used for about 30 day after surgery, but the patient's fever, bacteremia and watery diarrhea persisted. Considering the possibility of intestinal dysbiosis, we evaluated the structure and composition of the patient's fecal microbiota using 16S rDNA-based molecular techniques. As expected, the gut microbiota was extensively disrupted; therefore, a donor fecal suspension was delivered into the patient by nasoduodenal tube. The patient's clinical outcomes and shifts of the gut microbiota following the treatment were also determined.

Results: Dramatically, the patient's septic symptoms and severe diarrhea were successfully controlled following FMT. Her stool output markedly declined after 7 days and normalized 16 days after FMT. A significant modification in her microbiota composition was consistently seen, characterized by a profound enrichment of the commensals in Firmicutes and depletion of opportunistic organisms in Proteobacteria. Furthermore, we identified a reconstituted bacterial community enriched in Firmicutes and depleted of Proteobacteria members that was associated with fecal output, plasma markers of inflammation and T helper cells.

Conclusions: In this report, we describe our initial experience with FMT, in which we successfully used it in the treatment of a patient with sepsis and severe diarrhea after a vagotomy. Our data indicate an association between repaired intestinal microbiota barrier and improvement of clinical outcomes. Our patient's surprising clinical benefits from FMT demonstrate the role of intestinal microbiota in modulating immune equilibrium. It represents a breakthrough in the clinical management of sepsis and suggests new therapeutic avenues to pursue for microbiota-related indications.

Figures

Figure 1

Treatment timeline of the patient. The timeline shows the major clinical events during the course of the patient’s treatment. CRRT, Continuous renal replacement therapy; VV-ECMO, Venovenous extracorporeal membrane oxygenation; FMT, Fecal microbiota transplantation.

Figure 2

Molecular assessments of the fecal bacterial microbiota in the patient. (A) Representative fingerprints of denaturing gradient gel electrophoresis (DGGE) gels for fecal microbiota. The figures 1 to 32 represent the predominant bands for DNA sequencing. The closest bacterial phylotypes corresponding to these bands are shown in Additional file 5. (B) Dendrogram generated from our DGGE analysis. The clustering profiles were obtained from DGGE analysis using the unweighted pair group method with arithmetic average. The metric scale indicates the degree of similarity (%). D1 to D3 denote the fecal specimens from the donor. −5d, −1d and 0d to 21d represent the fecal samples collected from the patient 5 and 1 days before and 0 to 21 days after fecal microbiota transplantation, respectively. The 19d data are missing because there was no fecal output at 19 days after infusion of donor feces. (C) Plot generated from the relative abundance of DGGE bands depicting our principal component analysis of the patient’s fecal microbiota.

Figure 3

Determination of the predominant bacterial composition in the fecal microbiota at the phylum level. Representative time points were selected to show the variations of the microbiota composition following fecal microbiota transplantation.

Figure 4

Changes of the predominant bacterial composition at the family level after fecal microbiota transplantation.

Figure 5

Variations of the major bacterial species in the fecal microbiota after fecal microbiota transplantation.

Figure 6

Stool output of the patient and the association with specific bacterial phylogroups. (A) Variations of fecal output in the patient after fecal microbiota transplantation. Total volume of the stool was documented each day. (B) Correlations of the relative proportions of Firmicutes, Streptococcaceae, Proteobacteria and Enterobacteriaceae with stool output per day. Correlation between two variances was estimated using linear regression analysis with a Pearson test.

Figure 7

Serum levels of inflammatory mediators in the patient before and after fecal transplantation. (A) Graphs depict the serum levels of inflammatory mediators in the patient before and after fecal transplantation. All data are expressed as means of duplicates. The solid and dotted lines represent the mean values of serum concentrations in healthy subjects. (B) Representative histograms illustrate flow cytometry results as percentage of CD4+ T cells producing interferon γ (side scatter height (SSCH); IFN-γ; T helper type 1 (Th1)), interleukin (IL)-4 (Th2) and IL-17 (Th17). (C) Changes in T helper cell subpopulations in the patient before and after fecal transplantation are depicted.

Figure 8

Correlation analyses between specific bacterial phylogroups and immunological parameters. Graphs depicting the taxon abundance of many members within the phyla Firmicutes and Proteobacteria, which had strong associations with inflammatory markers (A) and the proportions of circulating Th cells (B). CRP, C-reactive protein; HMGB-1, High-mobility group box 1; IL, Interleukin; IFN, interferon; Th, T helper cell.