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

Christopher Staley, Colleen R Kelly, Lawrence J Brandt, Alexander Khoruts, Michael J Sadowsky

Journal: mBio 2017;7(6):e01965-16

PMID: 27999162

Plain Language Summary

Disruption of the intestinal microbial community, typically following antibiotics, enables proliferation of enteric pathogens such as Clostridium difficile. Research has indicated that several species of bacteria may play critical roles in maintaining resistance to recurrent Clostridium difficile infection (rCDI). This aim of this study is to provide a detailed characterisation of faecal bacteria communities in subjects with rCDI receiving faecal microbiota transplantation (FMT). A cohort of 24 participants were randomised to receive either the placebo, an autologous FMT, or a healthy donor heterologous FMT, and stool bacterial community was characterised and analysed. This study showed that specific bacteria could potentially provide resistance to infection. According to these results, the authors conclude this study provides greater insight on the efficacy of FMT and further describe the shifts in the microbiome associated with cure in the absence of donor material.

Abstract

UNLABELLED

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.

IMPORTANCE

This study provides a detailed characterization of fecal bacterial communities in subjects who participated in a previously published randomized clinical trial to treat recurrent C. difficile infection (rCDI). Bacterial communities were characterized to determine differences between subjects who received fecal bacteria either from healthy donor stool samples or their own stool samples as "placebo" in order to determine which groups of bacteria were most important in achieving a cure. The results of this study suggested that bacteria associated with secondary bile acid metabolism could potentially provide resistance to infection and that complete transfer of healthy donor microorganisms was not necessary to resolve CDI following unsuccessful antibiotic treatment.

Address: BioTechnology Institute, University of Minnesota, St. Paul, Minnesota, USA.; Department of Medicine, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.; Women's Medicine Collaborative, The Miriam Hospital, Providence, Rhode Island, USA.; Department of Medicine, Division of Gastroenterology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York, USA.; BioTechnology Institute, University of Minnesota, St. Paul, Minnesota, USA.; Division of Gastroenterology and Center for Immunology, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.; BioTechnology Institute, University of Minnesota, St. Paul, Minnesota, USA [email protected].; Department of Soil, Water, and Climate, University of Minnesota, St. Paul, Minnesota, USA.

DOI: 10.1128/mBio.01965-16

Physical Environment

Infectious Agents

Clinical Imbalances

Immune and inflammation Gastro-intestinal

Laboratory Testing

Stool

Modifiable Lifestyle Factors

Diet

Nutrition Evidence Keywords

FMT SourceTracker

Bioactive Substances

Clostridiumscindens

Link outs

Free resources

Full Text Sources:

Medical:

https://medlineplus.gov/bowelmovement.html

Other Literature Sources:

Research Materials:

https://antibodies.cancer.gov/detail/CPTC-HLA-B-1

MeSH Terms: Adult, Aged, Bacteroidetes, Bayes Theorem, Clinical Trials as Topic, Clostridioides difficile, Clostridium Infections, Diarrhea, Fecal Microbiota Transplantation, Feces, Female, Firmicutes, Gastrointestinal Microbiome, Healthy Volunteers, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Recurrence, Remission Induction