June 24, 2014
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Functional changes accompanied microbial structural changes after fecal microbiota transplant

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Specific changes in gut microbiota structure after fecal microbiota transplant in patients with recurrent Clostridium difficile infection were associated with functional changes in a recent study.

To determine the functional means by which fecal microbiota transplant (FMT) restores colonization resistance in patients with C. difficile infection (CDI), researchers performed 16S rRNA sequencing on pre- and post-FMT samples of 14 patients who had at least two recurrent CDI, as well as samples from 10 donors for comparison.

Total DNA extraction yielded 569,880 sequences (mean, 14,243 per sample) clustered into 1,796 operational taxonomic units (OTUs). Proteobacteria made up 48.2% of pre-FMT OTUs compared with 11.2% of post-FMT (P<.001) and 0.73% of donor OTUs (P<.0001). Cronobacter and Enterobacteriaceae composed 17.9% and 20.3% of pre-FMT OTUs, respectively, compared with a combined 8.8% of post-FMT and 0.12% of donor OTUs. Bacteroidetes constituted 1.3% of pre-FMT OTUs compared with 32.3% of post-FMT (P<.0001) and 32.8% (P<.0001) of donor OTUs. Fusobacteria undetectable in donor samples were detected in six pre-FMT and two post-FMT samples, while Akkermansia undetectable in pre-FMT samples were observed in six post-FMT and at high levels in the three donor samples.

Overall OTU diversity increased in post-FMT compared with pre-FMT (P<.01) and in donor compared with post-FMT samples (P<.01). Shared OTUs between post-FMT and donor samples was much greater than pre-/post-FMT (P<.0001) and pre-FMT/donor (P<.001) comparisons. Firmicutes and Bacteroidetes correlated with healthy post-FMT and donor status while Proteobacteria correlated with pre-FMT. Gene modules related to basic metabolism and biosynthesis of amino acids, nucleotides and carbohydrates were more abundant in donor and post-FMT samples compared with pre-FMT; those associated with stress response and peptide transport were more abundant in pre-FMT vs. donor and post-FMT samples (P<.01). Ultimately 12 (86%) participants achieved clinical recovery from CDI.

“By comparing community composition and structure per FMT pair, we observed differences in functional potential of the microbiome based on the type of community present within individual recipient-donor pairs,” the investigators wrote. “While current success rates are high for treatment of CDI, a clear understanding of how FMT works has the potential to aid the development of alternative biotherapeutics.”

Disclosure: Relevant financial disclosures were not provided by researchers.