A new study on the mechanisms involved in recovery from recurrent Clostridium difficile infection after faecal microbiota transplantation

Faecal microbiota transplantation (FMT) has been previously reported as an effective treatment for recurrent Clostridium difficile infection (rCDI). Preclinical and clinical data have shown that restoration of donor-like beta diversity (i.e. species diversity compared to another individual) did not always correspond to direct restoration of an individual’s alpha diversity (i.e. the mean species diversity on a local scale), which suggests that specific microbial species may be necessary for resistance to C. difficile. However, it is not clear which species these might be, nor to what extent particular microbes are essential for recovery.

A new study, led by Dr. Michael J. Sadowsky from the BioTechnology Institute and Department of Soil, Water, and Climate at the University of Minnesota (USA), has found that engraftment of a donor’s gut microbial community is not necessary for recovery from recurrent C. difficile infection after faecal microbiota transplantation.

In order to determine which bacteria were the most important in achieving a cure -described as a resolution of diarrhoea and no CDI recurrence throughout the 8-week follow-up period without the need for antibiotics-, the researchers characterized bacterial communities from a cohort of 24 subjects treated for rCDI with FMT—receiving either colonoscopic autologous FMT using their own stool (n = 14) or colonoscopic heterologous FMT using healthy donor stool (n = 10). All participants underwent a regimen of vancomycin for at least 10 days and the antibiotic was discontinued 2 or 3 days prior to FMT. Complete details about the methodology of the randomized controlled trial can be found here.

The success of heterologous FMT (90%) was superior to that of autologous FMT (43%), as expected. Several pre-FMT assemblages occurred among subjects treated with heterologous FMT and autologous FMT, Lactobacillus sp. being the only operational taxonomic unit that was common to all samples. Patients treated by autologous FMT had greater abundances of members of the Clostridium XIVa clade, as well as Holdemania and Parasutterella bacteria prior to the treatment, which suggests a relationship between the pre-FMT gut microbial communities and the clinical outcomes. Furthermore, the relative abundances of these bacterial groups increased significantly after FMT compared to heterologous FMT and pre-FMT samples.

Besides this, the composition of follow-up FMT samples at 2 and 8 weeks post-FMT differed significantly between subjects treated for rCDI by heterologous FMT and those treated by autologous FMT. When studying source contributions to communities’ distribution, patients initially treated by heterologous FMT had significantly higher percentages of engraftment compared to those who suffered recurrence following autologous FMT. According to the authors, “these results may suggest that the microbiome of subjects that were follow-up at 2 and 8 weeks post-FMT were more complex due to an initial autologous FMT, or it could indicate a more inhibitory effect of a second follow-up antibiotic regimen prior to follow-up FMT”. On the whole, complete donor engraftment may not be necessary for recovery if functionally critical taxa are present in subjects following antibiotic therapy.

In conclusion, we still do not know the mechanisms of therapeutic efficacy when it comes to FMT for recurrent C. difficile infection. Variation in gut microbial communities prior to FMT, and the source of FMT (donor stool or the patient’s own stool) seem to be important factors that may relate to clinical outcomes in the treatment of recurrent C. difficile infection.

 

 

Reference:

Staley C, Kelly CR, Brandt LJ, Khoruts A, Sadowsky MJ. Complete microbiota engraftment is not essential for recovery from recurrent Clostridium difficile infection following fecal microbiota transplantation. MBio. 2016; 7(6). doi: 10.1128/mBio.01965-16.

Andreu Prados
Andreu Prados
Andreu Prados holds a Bachelor of Science Degree in Pharmacy & Human Nutrition and Dietetics. Science writer specialised in gut microbiota and probiotics, working also as lecturer and consultant in nutrition and healthcare. Follow Andreu on Twitter @andreuprados