The Gut Microbiome in Health and in Disease

Andrew B. Shreiner; John Y. Kao; Vincent B. Young

Disclosures

Curr Opin Gastroenterol. 2015;31(1):69-75. 

In This Article

Clostridium Difficile Infection

Clostridium difficile infection (CDI) is the prime example of a human disease that develops as a result of critical changes to the gut microbiota and is effectively treated by microbiota-based therapy.[36] A meta-analysis to review the use of fecal microbiota transplant (FMT) for prevention of recurrent CDI identified 11 studies with 273 patients through 2012; the overall resulting efficacy was about 90% and no substantial FMT-related adverse events were reported.[37] In a prospective clinical trial, patients with recurrent CDI were randomly assigned to one of three treatment groups: standard vancomycin therapy, vancomycin therapy followed by bowel lavage, and vancomycin therapy followed by bowel lavage and subsequent infusion of donor stool into the duodenum.[38] The study was stopped early after interim analysis because of the superiority of FMT. Analysis of the fecal microbiota of patients who were treated with FMT for recurrent CDI demonstrated that the posttransplant microbiota of the recipients becomes more similar to that of the donor. After FMT, the recipient microbiota was characterized by increased diversity, increased abundance of various Firmicutes and Bacteroidetes, and decreased abundance of Proteobacteria.[39] In a proof-of-principle study,[40] two patients with CDI refractory to antibiotics were successfully treated with a stool substitute consisting of 33 strains of bacteria isolated and cultured from a healthy donor. In this study, the stool substitute was delivered with colonoscopy, but it does provide promise for using a selected population of bacteria that could be prepared in a laboratory. Collectively, these studies strongly support the treatment of recurrent CDI with microbiota-based therapies.

Although susceptibility to CDI after antibiotic use is associated with decreased microbiota diversity, little is known about the functional difference in the microenvironment that permits CDI. In preclinical studies, the microbiota changes that occurred after antibiotic treatment in mice susceptible to C. difficile were accompanied by changes in the metabolome that supported C. difficile germination and growth.[41] In the antibiotic-treated mice, primary bile acids that support C. difficile germination and certain carbohydrates that support C. difficile growth were present at significantly increased levels compared to control C. difficile-resistant mice. This study, and others, is helping to unravel the mechanism by which antibiotic-induced changes to the microbiota contribute to CDI, potentially leading to novel therapies for this burdensome disease.

processing....