Optimizing Fecal Microbiota Transplantations For Therapeutic Use Beyond Clostridioides difficile Infection
Abstract
Fecal microbiota transplantation (FMT) is an emerging and effective therapy for the treatment of recurrent Clostridioides difficile infection. Members of the gut microbiome have been implicated in other diseases and FMT has been considered as a potential therapy. Two such conditions include non-alcoholic fatty liver disease (NAFLD) and multiple sclerosis (MS), both of which involve increased small intestinal permeability believed to contribute to the development and disease progression. One of the aims of this project was to determine if FMT could be safely used in patients with NAFLD and MS to improve health outcomes. Before starting the clinical studies, optimal ways of storing and preparing stool for FMT were investigated with a goal of reducing loss of viable bacteria due to sample collection, handling, and storage. Bacterial culture and next-generation sequencing techniques were utilized to assess the impact of processing and storage. With optimal procedures in place, which included storing samples as whole stool at -80 °C for up to 3 months, FMT donor screening was expanded to extend beyond transmissible diseases to include lifestyle factors, and personal/family history of disease. From this, only 5 of 46 healthy potential donors qualified, and they provided stool for patients with NAFLD (n=21) and MS (n=10). All FMT recipients with elevated small intestinal permeability, determined using the lactulose:mannitol permeability assay, improved following FMT. Microbiota engraftment was detected in some patients. The treatment was safe and well tolerated in all recipients. With NAFLD being the second leading cause of liver transplant in North America and MS having no cure, the use of FMT could potentially contribute to the quality of life and reduction in comorbidities. Since current treatment options for both diseases are not particularly effective, and the rates are increasing, new approaches are needed. The current findings provide a basis for larger studies with earlier intervention and longer follow-up. In summary, the improvement in intestinal barrier function with FMT shows a novel mechanism for this therapy, and one that has implications for many conditions associated with abnormal intestinal permeability.