Comparison of Different Strategies for Providing Fecal Microbiota Transplantation to Treat Patients with Recurrent Clostridium difficile Infection in Two English Hospitals: A Review

Abstract

Fecal microbiota transplant (FMT) has emerged as a highly efficacious treatment for difficult cases of refractory and/or recurrent Clostridium difficile infection (CDI). There have been many well-conducted randomized controlled trials and thousands of patients reported in case series that describe success rates of approximately 90% following one or more FMT. Although the exact mechanisms of FMT have yet to be fully elucidated, replacement or restoration of a ‘normal’ microbiota (or at least a microbiota resembling those who have never had CDI) appears to have a positive effect on the gut dysbiosis that is thought to exist in these patients. Furthermore, despite being aesthetically unappealing, this ‘ultimate probiotic’ is a particularly attractive solution to a difficult problem that avoids repeated courses of antibiotics. The lack of clarity about the exact mechanism of action and the ‘active ingredient’ of FMT (e.g., individual or communities of bacteria, bacteriophage, or bioactive molecules such as bile acids) has hindered the ability to produce a standardized and well-characterized FMT product. There is no standard method to produce material for FMT, and there are a multitude of factors that can vary between institutions that offer this therapy. Only a few studies have directly compared clinical efficacy in groups of patients who have been treated with FMT prepared differently (e.g., fresh vs. frozen) or administered by different route (e.g., by nasojejunal tube, colonoscopy or by oral administration of encapsulated product). More of these studies should be undertaken to clarify the superiority or otherwise of these variables. This review describes the methods and protocols that two English NHS hospitals independently adopted over the same time period to provide FMT for patients with recurrent CDI. There are several fundamental differences in the methods used, including selection and testing of donors, procedures for preparation and storage of material, and route of administration. These methods are described in detail in this review highlighting differing practice. Despite these significant methodological variations, clinical outcomes in terms of cure rate appear to be remarkably similar for both FMT providers. Although both hospitals have treated only modest numbers of patients, these findings suggest that many of the described differences may not be critical factors in influencing the success of the procedure. As FMT is increasingly being proposed for a number of conditions other than CDI, harmonization of methods and techniques may be more critical to the success of FMT, and thus it will be important to standardize these as far as practically possible.

From Donor to Patient: Collection, Preparation and Cryopreservation of Fecal Samples for Fecal Microbiota Transplantation

“…It is not known whether a change of the microbiota following FMT has any long-term consequences. Despite a few worldwide existing stool banks, there is no standard method for producing material for FMT, and there are a multitude of factors that can vary between institutions offering this therapy [23]. To date, safety concerns and acceptability are the main constraints of therapeutic uses of FMT [24].…”

The case for stool banks in South Africa

“…[4] FMT involves the introduction of microbiota from a healthy donor to a patient by colonoscopy, enema or nasogastric tube. [5] Currently, CDI is the main indication for FMT, but as a novel treatment strategy, it has also been investigated in conditions ranging from inflammatory bowel disease to metabolic diseases, obesity, malnutrition and autism spectrum disorders. [6] To this end, the SA Gastroenterology Society (SAGES) published FMT guidelines in 2015.…”

CRISPRs for strain tracking and its application to microbiota transplantation data analysis

“…In an attempt to increase intestinal microbial diversity and re-establish a stable microbiome, fecal microbiota transplantation (FMT) has been applied to the treatment of recurrent CDI [6] and other gastrointestinal disorders [7]. The reported success rate of FMT based on thousands of patients with recurrent CDI is 90% following one or more FMT [8,9]. Although restoration of a microbiota appears to have a positive effect against gut dysbiosis that is thought to exist in these patients, the exact mechanisms of FMT have yet to be fully elucidated [8].…”

“…The reported success rate of FMT based on thousands of patients with recurrent CDI is 90% following one or more FMT [8,9]. Although restoration of a microbiota appears to have a positive effect against gut dysbiosis that is thought to exist in these patients, the exact mechanisms of FMT have yet to be fully elucidated [8]. In addition to gastrointestinal disorders, recent studies have shown promising applicaiton of FMT to treat other types of diseases, including Parkinson's disease [10] and autism [11].…”