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

The incidence of gastrointestinal infection, which results from MODS but also aggravates the disease, is relatively high in MODS patients, and gut microbiota imbalance may contribute to the infection [13]. Thus, FMT, which can help reconstruct the impaired gut microbiota barrier and correct the dysbiosis in patients in the ICU, has therapeutic potential for treating MODS [14, 15]. In this paper, we have reported two patients with sepsis, MODS, and severe diarrhea who were successfully treated by transplantation of fecal microbiota from a healthy donor. Our results are consistent with a previous case report of one patient with severe sepsis and diarrhea following vagotomy, who was successfully treated by FMT [16].

Recent studies have shown that the gut is the depot for bacteria and endotoxins associated with SIRS and MODS [7]. All elements of the gut – the epithelium, the immune system, and the microbiome – are impacted by critical illness, and can in turn propagate a pathologic host response [17]. Prior to FMT, the most notable changes in the fecal microbiota of patient 1 were increased Actinobacteria and decreased Firmicutes and Proteobacteria, and the most notable changes in the fecal microbiota of patient 2 were increased Bacteriodetes and Proteobacteria and decreased Firmicutes, compared with the fecal microbiota of the healthy donor. Because it makes up the largest part of the human gut microbiome and contains the genus Lactobacillus [18], the Firmicutes phylum could be beneficial to the normal function of the gastrointestinal tract. It is known that pathogenic bacteria translocate and proliferate more than the nonpathogenic ones, which can lead to gut barrier disruption, infection, and ultimately SIRS and MODS, by releasing multiple cytokines. The changes in microbiota composition observed in our patients could help further our understanding of the importance of maintaining a normal gut microbiota barrier and the feasibility of treating patients by restoring it.

Although FMT has been proposed as an effective method for correcting the dysbiosis among patients in the ICU and for restoring the normal gut microflora, its therapeutic role has not been completely explored [19, 20]. In our patients, the infection and diarrhea were alleviated by FMT, and the systemic immune response was also attenuated. The stool volume and frequency had increased significantly before FMT in both patients, but were gradually reduced after FMT. The stool was gradually formed. Here, we need to explain that at 3 days before FMT, we stopped all treatment with antibiotics in both of the patients so that the patients entered into an antibiotic washout period to prepare for later FMT. Because no antibiotics were present to further destroy the intestinal flora in this time range, the intestinal flora might recover somewhat. Therefore, the amounts of stool in the two patients fluctuated at 5 days before FMT. Sometimes the amounts were increased, sometimes they were decreased, and the overall trend was towards a decrease, but the stool frequencies in the two patients were still very high before FMT. In addition, there was no trend towards well-formed stool, and the overall composition of the stool was still similar to that of diarrhea. After being treated with FMT, the amounts of stool in the two patients were rapidly decreased, the stool frequencies were significantly decreased, and the stool gradually became well-formed. These findings indicate that the significant improvement in symptoms of diarrhea in the patients still depends on recovery of the balance of the intestinal flora due to FMT.

We observed decreased levels of IL-6, CRP, PCT, and ESR in both patients following FMT. An interesting phenomenon was seen in that although there was a trend towards a decrease in the overall levels of inflammatory factors such as IL-6 and CRP, the levels fluctuated somewhat in the first few days. A similar pattern was observed for PCT and ESR. However, all of these were minor changes. We hypothesize that these changes may be correlated with restoration of the intestinal flora and the improvement in clinical symptoms to some extent in patients after we stopped using antibiotics before FMT. The trend towards a decrease in these inflammatory factors also indicates that FMT might play an important role in the regulation of the immune system [21].

In an effort to identify a possible mechanism underlying the clinical benefits achieved in our patients, we evaluated the temporal changes in the microbiota composition following FMT. We further identified the variations in the composition of the microbiota in our patients following FMT under different OTU annotation levels. By comparing the fecal microbiota before and after FMT, we observed a transition to normal quantities (patient 1) or to a normal distribution (patient 2) of the aforementioned bacterial phyla found to be imbalanced (when compared with those in the healthy donor) before FMT, which is of valuable clinical significance. Changes in the proportions of fecal microbiota at the class, order, family, and genus levels were also observed in both patients following FMT, and these altered proportions tended to approach those of the donor. These findings suggest that reshaping the gut microbiota might be the fundamental mechanism of FMT in treating sepsis-associated MODS and that FMT is capable of restoring the normal quantities and/or the normal distribution of intestinal microbiota in patients with MODS.