Recovery of the Gut Microbiome following Fecal Microbiota Transplantation

Abstract

Clostridium difficile infection is one of the most common health care-associated infections, and up to 40% of patients suffer from recurrence of disease following standard antibiotic therapy. Recently, fecal microbiota transplantation (FMT) has been successfully used to treat recurrent C. difficile infection. It is hypothesized that FMT aids in recovery of a microbiota capable of colonization resistance to C. difficile. However, it is not fully understood how this occurs. Here we investigated changes in the fecal microbiota structure following FMT in patients with recurrent C. difficile infection, and imputed a hypothetical functional profile based on the 16S rRNA profile using a predictive metagenomic tool. Increased relative abundance of Bacteroidetes and decreased abundance of Proteobacteria were observed following FMT. The fecal microbiota of recipients following transplantation was more diverse and more similar to the donor profile than the microbiota prior to transplantation. Additionally, we observed differences in the imputed metagenomic profile. In particular, amino acid transport systems were overrepresented in samples collected prior to transplantation. These results suggest that functional changes accompany microbial structural changes following this therapy. Further identification of the specific community members and functions that promote colonization resistance may aid in the development of improved treatment methods for C. difficile infection.

Clostridium difficile and the microbiota

“…These results are in agreement with the in vitro and in vivo mouse studies that have previously observed that secondary bile acids, such as lithocholic or deoxycholic acid, inhibit C. difficile growth (20,25). Although the bacterial community is responsible for producing the metabolic environment, it is possible that several types of bacterial communities with similar functions may be capable of the same metabolic outcome, and that structure alone may not be enough to determine recurrence risk (82).…”

Fecal microbiota transplantation in children: a brief review

“…The intestinal microbiome of children, especially the very young, is known to differ from adults yet there is very little data characterizing associated microbiome changes with FMT in children. Microbiome changes have been reported in a 20-mo-old boy (28), with decreased diversity of the microbiome prior to FMT, with a relative abundance of Proteobacteria, with increased diversity after FMT with increasing Bacteroidetes; these are similar changes to those previously described in adults (39,42). Additionally, in a case series of older children increased microbiome diversity after FMT for CDI appears to be sustained in those without IBD, however at 6 mo decreases to pre-FMT baseline in those with IBD, suggesting IBD hostrelated mechanisms may modify fecal microbiome diversity (29).…”

Identifying strains that contribute to complex diseases through the study of microbial inheritance

“…With the advent of next-generation sequencing, there has been an explosive increase in the use of this phylogenetic marker to characterize microbial communities in the environment and those associated with the body habitats of myriad animal species, including our own. The increasing ease and economy of defining human microbial ecology within and across individuals has spawned many studies that have sought to correlate community membership with health status (3)(4)(5)(6)(7)(8)(9). These studies have highlighted the variation in microbial diversity between body habitats in a given individual and intrapersonal variation in community membership within a given habitat over time, as well as substantial interpersonal differences.…”