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

Li et al. Critical Care Successful treatment of severe sepsis and diarrhea after vagotomy utilizing fecal microbiota transplantation: a case report Qiurong Li 0 Chenyang Wang 0 Chun Tang 0 Qin He 0 Xiaofan Zhao 0 Ning Li 0 Jieshou Li 0 0 Research Institute of General Surgery, Jinling Hospital, Nanjing University School of Medicine , No.305 East Zhongshan Road, Nanjing 210002 , China 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. - Introduction The mucosal surface of the gastrointestinal tract is colonized by a complex ecosystem of commensal microbiota that mediates homeostatic effects on the host and shapes aspects of host metabolism, immune functions and protection against invasion by pathogens [1-3]. It is now well appreciated that the intestinal microbiota constitutes an efficient microbial barrier against infections and is critical to the host antimicrobial defense. Protracted loss of the typical microbiota composition has been associated with exposure to antibiotics, inflammation and several disorders, including inflammatory bowel disease [4,5]. Recurrent Clostridium difficile infection (CDI) is thought to result from persistent disruption of commensal gut microbiota [6]. The reestablishment of intestinal microbiota balance is needed in a curative approach for therapy. Recently, fecal microbiota transplantation (FMT) has emerged as a critical treatment for recurrent CDI [7,8]. However, whether an ecologically stable microbial population is restored and the nature of the transition remain to be elucidated. Sepsis is one of the leading causes of mortality in the intensive care unit (ICU), with rates of approximately 50% to 60% in patients who develop septic shock and 30% to 50% in those who develop severe sepsis [9,10]. Therapy for severe sepsis is still largely supportive and based on symptoms. The commensal enteric microbiota constitutes a pivotal microbial barrier that protects against opportunistic pathogen invasion [1-3]. The gut microbiota is essential for the maintenance of mucosal immune homeostasis [2]. Impairment of the microbial barrier may allow enteric bacteria to cause sepsis [11]. Intestinal microbiota dysbiosis is often seen in patients with sepsis, suggesting its possible contribution in the initiation and/or perpetuation of the disease [12,13]. Regulation of gut microbiota is a delicate balancing act. Given the intestinal dysbiosis and its prominent role in the development of sepsis, improved clinical outcomes may be achieved with FMT in patients with sepsis. However, experience with this procedure in sepsis remains limited. The efficacy of FMT in recurrent CDI encouraged us to investigate the therapeutic value of the strategy in patients with sepsis and the underlying mechanisms. In this article, we describe a case of a patient who developed septic shock and severe diarrhea following vagotomy and report our findings regarding FMT. We also sought to investigate the changes in the identity and abundance of the bacteria in gut microbial communities and to assess relationships between these assemblages and immunologic signatures of the sepsis patient. Jinling Hospital (the ethics committee of our hospital). The patient gave us her written informed consent to undergo the procedure and to have her case published. Case presentation Our patient was a 44-year-old woman who underwent proximal gastrectomy and bilateral truncal vagotomy for a gastric neuroendocrine tumor. Her immediate postoperative course was uneventful, and no surgical complications, such as anastomotic fistula, were observed. On the third postoperative day, she presented with abdominal discomfort and bloating, nausea and vomiting (Figure 1). On the fourth postoperative day, the patient developed severe, watery diarrhea. Her blood pressure suddenly decreased to 60/38 mmHg for unknown reason. An examination revealed that her body temperature was 37.2C, her pulse was increased at 126 beats/minute, her respiratory rate was 28 breaths/minute and her blood oxygen saturation was 86%. A complete blood count was obtained, and the results revealed a white blood cell count of 2.9 109/L with 83% neutrophils and 13% lymphocytes. Analysis of blood gas showed that the patients blood lactate level was 8.2 mmol/L and base excess was 9.2. Serum level of C-reactive protein (CRP) was 143.4 mg/L. Blood and urine were collected for bacterial culture, and both test results were negative. The patient was urgently transferred to the ICU. On the fifth postoperative day, her temperature rose to 39.6C and her pulse rate was 145 beats/minute, and she developed (...truncated)