Gastrointestinal dysbiosis and the use of fecal microbial transplantation in Clostridium difficile infection

Abstract

The impact of antibiotics on the human gut microbiota is a significant concern. Antibiotic-associated diarrhea has been on the rise for the past few decades with the increasing usage of antibiotics. Clostridium difficile infections (CDI) have become one of the most prominent types of infectious diarrheal disease, with dramatically increased incidence in both the hospital and community setting worldwide. Studies show that variability in the innate host response may in part impact upon CDI severity in patients. That being said, CDI is a disease that shows the most prominent links to alterations to the gut microbiota, in both cause and treatment. With recurrence rates still relatively high, it is important to explore alternative therapies to CDI. Fecal microbiota transplantation (FMT) and other types of bacteriotherapy have become exciting avenues of treatment for CDI. Recent clinical trials have generated excitement for the use of FMT as a therapeutic option for CDI; however, the exact components of the human gut microbiota needed for protection against CDI have remained elusive. Additional investigations on the effects of antibiotics on the human gut microbiota and subsequent CDI will help reduce the socioeconomic burden of CDI and potentially lead to new therapeutic modalities.

Keywords: Antibiotic-associated diarrhea; Bacteriotherapy; Dysbiosis; Fecal microbial transplant; Human gut microbiota.

Figure 1

Pathogenesis of Clostridium difficile infections. Clostridium difficile (C. difficile) spores are ingested and pass through the stomach, upon which they can interact with taurocholate within the small intestine and germinate into vegetative cells (1); Vegetative cells then colonize within the gut microbiota (2) and begin to produce toxins, TcdA and TcdB (3); Toxins cause epithelial damage and pro-inflammatory cytokine release, leading to infiltration of neutrophils that cause pseudomembranous colitis (4).