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

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.

Community dynamics drive punctuated engraftment of the fecal microbiome following transplantation using freeze-dried, encapsulated fecal microbiota

“…14,24 The percentage of engraftment through later time points corresponded with increases in the members of the Bacteroidetes, including members of the genera Bacteroides, Parabacteroides, and Alistipes, which were initially found at low abundances. Thus, it is likely that the majority of the donor assemblage was transferred at the time of the initial capsule FMT, but taxa were maintained at lower abundance due to difficulty resuscitating, perhaps as a result of gastrointestinal transit; injury of strict anaerobic microbiota during the preparation, freeze-drying, the encapsulation processes; or other host-associated factors.…”

Modulating bile acid pathways and TGR5 receptors for treating liver and GI diseases

“…Moreover, administration of UDCA eradicated C. difficile infection in a patient with recurrent pouchitis (29). Indeed, it has been shown in experimental animal studies that complete microbial engraftment following fecal microbiota transplantation is not required to recover from recurrent C. difficile infection, and bile acid metabolism with formation of secondary bile acids (who typically harbored greater relative abundance of members of the Clostridium XIVa clade or Holdemania in the family Erysipelotrichaceae ) could potentially provide resistance to the infection (30). …”

Bile acid disease

“…Moreover, administration of UDCA eradicated C. difficile infection in a patient with recurrent pouchitis [16]. Complete microbial engraftment following FMT is not required to recover from recurrent C. difficile infection, and secondary BA metabolism could potentially provide resistance to infection [17]. Subjects cured by autologous FMT typically harbored greater relative abundance of members of the Clostridium XIVa clade or Holdemania in the family Erysipelotrichaceae , as well as Parasutterella pre-FMT.…”

“…Subjects cured by autologous FMT typically harbored greater relative abundance of members of the Clostridium XIVa clade or Holdemania in the family Erysipelotrichaceae , as well as Parasutterella pre-FMT. The authors proposed that subjects who recovered following autologous FMT may have done so, at least in part, because of the presence of taxa active in secondary BA biosynthesis [17]. …”