The normal function of the gastrointestinal tract is important for immune defense against pathogens in the human body. It is now 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]. Recently, it has been shown that FMT can cure recurrent
Clostridium difficile infection (CDI), which results from persistent disruption of commensal gut microbiota, by reestablishing the intestinal microbiota balance [
5]. However, 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.
Multiple organ dysfunction syndrome (MODS), which in most cases occurs secondary to severe sepsis or septic shock, trauma, neoplastic diseases, and other causes of systemic inflammatory response syndrome (SIRS), refers to the presence of impaired function in multiple organs so that homeostasis cannot be maintained without medical intervention [
6]. The pathophysiology of MODS is complex, multifactorial, and poorly understood. Emerging evidence suggests that translocation of microbes or components of microbes from the gastrointestinal tract and immune system dysregulation might be involved [
7]. Thus, FMT might play a therapeutic role in the management of MODS following severe sepsis. The efficacy of FMT in treating recurrent CDI further encouraged us to investigate the value of this therapeutic approach in patients with MODS after sepsis. In this article, we describe two cases of patients who developed MODS and severe diarrhea following severe sepsis and report their outcomes following treatment with FMT. We also investigated the changes in composition and abundance of intestinal bacteria in these patients with MODS in response to FMT and characterized the relationship between these FMT-induced alterations in gut microbiota and immunological marker profiles.
Case presentation
Case 1: a 65-year-old male patient with sudden loss of consciousness and an initial diagnosis of encephalorrhagia was transferred to our hospital from another medical facility. Cerebral computed tomography (CT) confirmed the diagnosis of cerebellar hemorrhage. This patient was then admitted to the Department of Neurosurgery, and the cerebellar hematoma was surgically removed via the posterior middle approach. After surgery, the patient was in a persistent light coma, but defecation was normal. At 6 days post surgery, the patient was passing yellow pasty stool once a day, but this frequency later increased to 3–4 times a day.
On postoperative day 8, the patient developed pulmonary infection and progressed to acute respiratory distress syndrome (ARDS), then suffered type I respiratory failure. This patient went into a coma after the operation and had intermittent irritability and much airway mucus; therefore, it was considered that the pulmonary infection was more severe. Thus, in order to aspirate the sputum and maintain airway patency, we carried out a tracheotomy. The patient was admitted to the intensive care unit (ICU) with a diagnosis of septic shock and MODS. The acute physiology and chronic health evaluation (APACHE) II score was 23, and the white blood cell (WBC) count increased to 26.22 × 109/L with 84.2 % neutrophils. His blood cultures now yielded Acinetobacter baumannii. The patient had a persistently high fever, with a peak temperature of 39.6 °C, despite administration of antibacterial and antifungal therapy. Meanwhile, the sputum culture showed mycotic infection, so oral itraconazole was added. However, the patient’s condition continued to worsen.
On the 20th day of hospitalization, the patient developed septic shock. Antibiotics were changed to imipenem/cilastatin and vancomycin, while itraconazole was continued. The patient then had progressive diarrhea on average 6–12 times a day, with a total volume of 1000–2200 mL per day, with stool of a pasty jam consistency. We carried out comprehensive bacteriological investigations, including stool bacterial culture and fungal culture, and tested for Clostridium difficile toxin A and B. All results were negative. The fecal bacteria population was analyzed, and the results indicated severely perturbed intestinal microflora. Based on the above findings, this patient was rendered a good candidate for treatment with FMT. Therefore, FMT was performed once, and the anti-infection therapy was stopped.
Case 2: an 84-year-old male patient with right-sided weakness and fever was admitted. CT confirmed the presence of cerebral infarction near the left lateral ventricle and pulmonary infection. The patient was then transferred to ICU due to infection-induced respiratory failure. His blood cultures now yielded Burkholderia cepacia. Antibiotics were changed from imipenem/cilastatin to cefoperazone/sulbactam. On the fourth day of hospitalization, fluconazol was added due to the discovery of pseudohyphae in the sputum. The pneumonia improved, but the patient suffered from fever and diarrhea after the use of multiple antibiotics. The anti-infection therapy was ineffective. In addition, metronidazole, probiotics, and loperamide were useless in treating the diarrhea. Consequently, the patient’s fever persisted, and he progressed to MODS. His APACHE II score was 20. Continuous hemofiltration was given for aggravated renal failure on the seventh day of hospitalization. The patient had diarrhea 4–8 times a day, with a total stool volume of 1000–2000 mL per day. We carried out comprehensive bacteriological investigations for this patient too, including stool bacterial culture and fungal culture, and tested for C. difficile toxin A and B. All results were negative. As was the case for the first patient, analysis of the fecal bacteria indicated severe microflora imbalance and thus, a likelihood of successful treatment with FMT. Based on the experience of treating the first patient, the same FMT regimen was administered to this patient.