Abstract
ABSTRACTBacterial 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.
Highlights
The endogenous intestinal microbial community is comprised of commensal species, primarily bacteria within the phyla Firmicutes and Bacteroidetes, that play a critical role in human health by facilitating nutrient metabolism and protecting against pathogen colonization [1]
Neither Shannon nor abundance-based coverage estimate (ACE) indices differed among samples from subjects who were cured by autologous fecal microbiota transplantation (FMT) and those treated with heterologous FMT (P Ն 0.075)
FMT has been previously shown to restore bile acid metabolism in subjects with Recurrent C. difficile infection (CDI) (rCDI), who are deficient in secondary bile acid production [30], and fecal concentrations of secondary bile acids have been shown to inhibit germination and vegetative growth of C. difficile [31]
Summary
The endogenous intestinal microbial community is comprised of commensal species, primarily bacteria within the phyla Firmicutes and Bacteroidetes, that play a critical role in human health by facilitating nutrient metabolism and protecting against pathogen colonization [1]. Over the last several decades, the morbidity, severity, and fatality statistics for C. difficile infection (CDI) have been on the rise [5,6,7], and this has been attributed, in part, to the emergence of hypervirulent C. difficile strains with the NAP1/ BI/ribotype 027 genotype These hypervirulent clostridia show greater resistance to antibiotics and increased toxin production [8, 9]. Members of the intestinal microbial community have previously been shown to effectively impair, or prevent, growth of C. difficile in vitro [15], and a recent study has identified several species, including Clostridium scindens, that may play a primary role in resistance to C. difficile infection by production of secondary bile acids [16]. A study in mice and humans found that restoration of donor-like beta diversity, i.e., expansion of Firmicutes and Bacteroidetes, did not always correspond to direct restoration of an individual’s alpha diversity (species richness and evenness), suggesting that specific species may be necessary for resistance to C. difficile [16]
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