New Study Uncovers Important Principles of Fecal Transplant Therapy in Patients with Recurrent C.Diff Infection
Summary by Katie E. Golden, MD
Fecal microbiota transplantation (FMT), in which donor feces is transplanted into a recipient’s intestinal tract, has emerged as a promising treatment for both infectious and autoimmune diseases. This therapy has shown impressive efficacy in treatment of recurrent Clostridium difficile (C.diff) infection (curing 85% of cases), prompting research that suggests it may also be effective in inflammatory bowel disease, metabolic syndrome, and and even autism. Given our evolving understanding of how the gut microbiota has significant implications for human health and immunity, it follows naturally that restoring gut homeostasis through FMT has significant therapeutic value.
Despite the proven efficacy and potential of FMT, however, we still do not understand how to predict which bacterial species will engraft and colonize the host, and the clinical implications of this selection process. In this study, researchers investigate the current use of FMT in C.diff infection to better define the governing factors of fecal transplantation. They then use this data develop a statistical model to predict which bacterial species successfully engraft in the host.
The researchers followed 19 patients with recurrent C.diff infection, and analyzed stool samples from fecal donors, as well as from the patient before and after treatment. They analyzed the samples using higher resolution metagenomic sequencing, which allowed them to study engraftment of individual bacterial strains, and were subsequently able to develop a statistical model to accurately predict which strains would ultimately colonize the host. Remarkably, their model even predicted engraftment of bacterial strains that were not present in either the donor or host prior to treatment.
Researchers then used their statistical model to build ‘Strain Finder’, a novel technology that infers bacterial strain genotypes and frequencies in the host microbiome, and tracks them over time. They found that the most important determinant of engraftment was bacterial abundance and phylogeny (aka, its taxonomic identity) in both the donor and the patient before transplantation. Interestingly, clinical factors, such as use of antibiotics or immunosuppressants prior to treatment, did not predict colonization. The investigators, furthermore, validated their findings in metabolic syndrome, to suggest these governing principles of engraftment extend to other diseases processes.
This investigation made important strides in elucidating the fundamental principles governing bacterial engraftment after FMT. It provides a critical insight into the host and donor factors that contribute to treatment efficacy, thus paving the way for more targeted therapies via human gut microbiota engineering.