Complete Microbiota Engraftment Is Not Essential for Recovery from Recurrent Clostridium difficile Infection following Fecal Microbiota Transplantation

Abstract

ABSTRACT Bacterial communities from subjects treated for recurrent Clostridium difficile infection (rCDI) by fecal microbiota transplantation (FMT), using either heterologous donor stool samples or autologous stool samples, were characterized by Illumina next-generation sequencing. As previously reported, the success of heterologous FMT (90%) was superior to that of autologous FMT (43%) ( P = 0.019), and post-FMT intestinal bacterial communities differed significantly between treatment arms ( P < 0.001). Subjects cured by autologous FMT typically had greater abundances of the Clostridium XIVa clade and Holdemania bacteria prior to treatment, and the relative abundances of these groups increased significantly after FMT compared to heterologous FMT and pre-FMT samples. The typical shift to post-FMT, donor-like assemblages, featuring high relative abundances of genera within the Bacteroidetes and Firmicutes phyla, was not observed in the autologous FMT subjects. Autologous FMT patient bacterial communities were significantly different in composition than those for heterologous FMT patients and donors ( P < 0.001). The SourceTracker program, which employs a Bayesian algorithm to determine source contributions to sink communities, showed that patients initially treated by heterologous FMT had significantly higher percentages of engraftment (i.e., similarity to donor communities, mean value of 74%) compared to those who suffered recurrence following autologous FMT (1%) ( P ≤ 0.013). The findings of this study suggest that complete donor engraftment may be not necessary if functionally critical taxa are present in subjects following antibiotic therapy. IMPORTANCE This study provides a detailed characterization of fecal bacterial communities in subjects who participated in a previously published randomized clinical trial to treat recurrent C. difficile infection (rCDI). Bacterial communities were characterized to determine differences between subjects who received fecal bacteria either from healthy donor stool samples or their own stool samples as “placebo” in order to determine which groups of bacteria were most important in achieving a cure. The results of this study suggested that bacteria associated with secondary bile acid metabolism could potentially provide resistance to infection and that complete transfer of healthy donor microorganisms was not necessary to resolve CDI following unsuccessful antibiotic treatment.