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. IMPORTANCE Within the last decade, Clostridium difficile infection has surpassed other bacterial infections to become the leading cause of nosocomial infections. Antibiotic use, which disrupts the gut microbiota and its capability in providing colonization resistance against C. difficile, is a known risk factor in C. difficile infection. In particular, recurrent C. difficile remains difficult to treat with standard antibiotic therapy. Fecal microbiota transplantation (FMT) has provided a successful treatment method for some patients with recurrent C. difficile infection, but its mechanism and long-term effects remain unknown. Our results provide insight into the structural and potential metabolic changes that occur following FMT, which may aid in the development of new treatment methods for C. difficile infection.

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Fecal Microbiota Transplantation: Redefining Surgical Management of Refractory Clostridium difficile Infection

Clinics in Colon and Rectal Surgery ◽

10.1055/s-0040-1701233 ◽

2020 ◽

Vol 33 (02) ◽

pp. 092-097 ◽

Cited By ~ 2

Author(s):

Yao-Wen Cheng ◽

Monika Fischer

Keyword(s):

Clostridium Difficile ◽

Antibiotic Therapy ◽

Surgical Management ◽

Salvage Therapy ◽

Healthy Donor ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Clostridioides Difficile ◽

Clostridioides Difficile Infection ◽

Cure Rates

AbstractFecal microbiota transplantation (FMT) is the process of transplanting stool from a healthy donor into the gut of a diseased individual for therapeutic purposes. It has a clearly defined role in the treatment of recurrent Clostridium difficile (reclassified as “Clostridioides difficile”) infection (CDI), with cure rates over 90% and decreased rates of subsequent recurrence compared with anti-CDI antibiotics. There is emerging evidence that FMT is also effective in the treatment of severe and fulminant CDI, with associated decreases in mortality and colectomy rates compared with standard antibiotic therapy. FMT shows promise as salvage therapy for critically-ill CDI patients refractory to maximum medical therapy and not deemed to be surgical candidates. FMT should be considered early in the course of severe CDI and should be delivered immediately in patients with signs of refractory CDI. Expansion of FMT's use along the spectrum of CDI severity has potential to decrease associated rates of mortality and colectomy.

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Environmental Contamination in Households of Patients with Recurrent Clostridium difficile Infection

Applied and Environmental Microbiology ◽

10.1128/aem.03888-15 ◽

2016 ◽

Vol 82 (9) ◽

pp. 2686-2692 ◽

Cited By ~ 21

Author(s):

Megan K. Shaughnessy ◽

Aleh Bobr ◽

Michael A. Kuskowski ◽

Brian D. Johnston ◽

Michael J. Sadowsky ◽

...

Keyword(s):

Clostridium Difficile ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Hospital Environment ◽

Molecular Characteristics ◽

Species Identity ◽

Fecal Samples ◽

Content Type ◽

Environmental Surfaces ◽

Household Environment

ABSTRACTRecurrentClostridium difficileinfection (R-CDI) is common and difficult to treat, potentially necessitating fecal microbiota transplantation (FMT). AlthoughC. difficilespores persist in the hospital environment and cause infection, little is known about their potential presence or importance in the household environment. Households of R-CDI subjects in the peri-FMT period and of geographically matched and age-matched controls were analyzed for the presence ofC. difficile. Household environmental surfaces and fecal samples from humans and pets in the household were examined. Households of post-FMT subjects were also examined (environmental surfaces only). Participants were surveyed regarding their personal history and household cleaning habits. Species identity and molecular characteristics of presumptiveC. difficileisolates from environmental and fecal samples were determined by using the Pro kit (Remel, USA), Gram staining, PCR, toxinotyping,tcdCgene sequencing, and pulsed-field gel electrophoresis (PFGE). Environmental cultures detectedC. difficileon ≥1 surface in 8/8 (100%) peri-FMT households, versus 3/8 (38%) post-FMT households and 3/8 (38%) control households (P= 0.025). The most commonC. difficile-positive sites were the vacuum (11/27; 41%), toilet (8/30; 27%), and bathroom sink (5/29; 17%).C. difficilewas detected in 3/36 (8%) fecal samples (two R-CDI subjects and one household member). Nine (90%) of 10 households with multipleC. difficile-positive samples had a single genotype present each. In conclusion,C. difficilewas found in the household environment of R-CDI patients, but whether it was found as a cause or consequence of R-CDI is unknown. If household contamination leads to R-CDI, effective decontamination may be protective.

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Fecal Microbiota Transplantation Eliminates Clostridium difficile in a Murine Model of Relapsing Disease

Infection and Immunity ◽

10.1128/iai.00459-15 ◽

2015 ◽

Vol 83 (10) ◽

pp. 3838-3846 ◽

Cited By ~ 62

Author(s):

Anna M. Seekatz ◽

Casey M. Theriot ◽

Caitlyn T. Molloy ◽

Katherine L. Wozniak ◽

Ingrid L. Bergin ◽

...

Keyword(s):

Clostridium Difficile ◽

Gut Microbiota ◽

Murine Model ◽

Fecal Microbiota Transplantation ◽

Clinical Signs ◽

Fecal Microbiota ◽

Content Type ◽

Health Care Associated Infections ◽

Specific Community

RecurrentClostridium difficileinfection (CDI) is of particular concern among health care-associated infections. The role of the microbiota in disease recovery is apparent given the success of fecal microbiota transplantation (FMT) for recurrent CDI. Here, we present a murine model of CDI relapse to further define the microbiota recovery following FMT. Cefoperazone-treated mice were infected withC. difficile630 spores and treated with vancomycin after development of clinical disease. Vancomycin treatment suppressed bothC. difficilecolonization and cytotoxin titers. However,C. difficilecounts increased within 7 days of completing treatment, accompanied by relapse of clinical signs. The administration of FMT immediately after vancomycin clearedC. difficileand decreased cytotoxicity within 1 week. The effects of FMT on the gut microbiota community were detectable in recipients 1-day posttransplant. Conversely, mice not treated with FMT remained persistently colonized with high levels ofC. difficile, and the gut microbiota in these mice persisted at low diversity. These results suggest that full recovery of colonization resistance againstC. difficilerequires the restoration of a specific community structure.

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Durable Long-Term Bacterial Engraftment following Encapsulated Fecal Microbiota Transplantation To Treat Clostridium difficile Infection

mBio ◽

10.1128/mbio.01586-19 ◽

2019 ◽

Vol 10 (4) ◽

Cited By ~ 14

Author(s):

Christopher Staley ◽

Thomas Kaiser ◽

Byron P. Vaughn ◽

Carolyn Graiziger ◽

Matthew J. Hamilton ◽

...

Keyword(s):

Clostridium Difficile ◽

Healthy Donor ◽

Fecal Microbiota Transplantation ◽

Rescue Therapy ◽

Specific Effect ◽

Fecal Microbiota ◽

Rrna Gene ◽

Content Type ◽

Freeze Dried

ABSTRACT Fecal microbiota transplantation (FMT) has become a common rescue therapy for recurrent Clostridium difficile infection, and encapsulated delivery (cFMT) of healthy donor microbiota shows similar clinical efficacy as more traditional routes of administration. In this study, we characterized long-term patterns of bacterial engraftment in a cohort of 18 patients, who received capsules from one of three donors, up to 409 days post-FMT. Bacterial communities were characterized using Illumina sequencing of the V5-V6 hypervariable regions of the 16S rRNA gene, and engraftment was determined by using the Bayesian algorithm SourceTracker. All patients recovered clinically and were free of C. difficile infection following cFMT. The majority of patients (61%) showed high levels of engraftment after the first week following FMT, which were sustained throughout the year. A small subset, 22%, experienced a decline in donor engraftment after approximately 1 month, and a few patients (17%), two of whom were taking metformin, showed delayed and low levels of donor engraftment. Members of the genera Bacteroides, Parabacteroides, and Faecalibacterium were significantly and positively correlated with donor similarity (ρ = 0.237 to 0.373, P ≤ 0.017). Furthermore, throughout the year, patient fecal communities showed significant separation based on the donor fecal microbiota that they received (P < 0.001). Results of this study, which characterize long-term engraftment following cFMT, suggest that numerical donor similarity is not strictly related to clinical outcome and identify a persistent donor-specific effect on patient fecal microbial communities. Furthermore, results suggest that members of the Bacteroidetes may be important targets to improve engraftment via cFMT. IMPORTANCE Recurrent Clostridium difficile infection (rCDI) is the most common cause of hospital- and community-acquired diarrheal infection associated with antibiotic use. Fecal microbiota transplantation (FMT), a treatment that involves administration of fecal bacteria from a healthy donor to a recipient patient, is a highly effective rescue therapy for rCDI that is increasingly being incorporated into standard clinical practice. Encapsulated, freeze-dried preparations of fecal microbiota, administered orally, offer the simplest and most convenient route of FMT delivery for patients (cFMT). In this study, we evaluated the extent of bacterial engraftment following cFMT and the duration of donor bacterial persistence. All patients studied recovered clinically but showed differing patterns in long-term microbial community similarity to the donor that were associated with members of the bacterial group Bacteroidetes, previously shown to be prominent contributors to rCDI resistance. Results highlight long-lasting, donor-specific effects on recipient patient microbiota and reveal potential bacterial targets to improve cFMT engraftment.

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Fecal Microbiota Transplantation and Successful Resolution of Multidrug-Resistant-Organism Colonization

Journal of Clinical Microbiology ◽

10.1128/jcm.00820-15 ◽

2015 ◽

Vol 53 (6) ◽

pp. 1986-1989 ◽

Cited By ~ 61

Author(s):

Nancy F. Crum-Cianflone ◽

Eva Sullivan ◽

Gonzalo Ballon-Landa

Keyword(s):

Clostridium Difficile ◽

Fecal Microbiota Transplantation ◽

Multidrug Resistant ◽

Fecal Microbiota ◽

Resistant Organism ◽

Content Type ◽

Multidrug Resistant Organisms ◽

Successful Resolution ◽

Potential Measure

We report a case in which fecal microbiota transplantation (FMT) utilized for relapsingClostridium difficilecolitis successfully eradicated colonization with several multidrug-resistant organisms (MDROs). FMT may have an additive benefit of reducing MDRO carriage and should be further investigated as a potential measure to eradicate additional potentially virulent organisms beyondC. difficile.

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Laboratory Testing of Donors and Stool Samples for Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection

Journal of Clinical Microbiology ◽

10.1128/jcm.02327-16 ◽

2017 ◽

Vol 55 (4) ◽

pp. 1002-1010 ◽

Cited By ~ 26

Author(s):

Michael H. Woodworth ◽

Emma M. Neish ◽

Nancy S. Miller ◽

Tanvi Dhere ◽

Eileen M. Burd ◽

...

Keyword(s):

Clostridium Difficile ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Fecal Material ◽

Content Type ◽

Fda Guidance ◽

Recurrent Clostridium Difficile Infection ◽

Regulatory Changes ◽

Laboratory Screening ◽

Stool Samples

ABSTRACT Fecal microbiota transplantation is an efficacious and inexpensive therapy for recurrent Clostridium difficile infection, yet its safety is thought to depend on appropriate fecal donor screening. FDA guidance for regulation of this procedure is in flux, but screening and manufacture of fecal material from asymptomatic donors present many challenges to clinical laboratories. This minireview summarizes FDA regulatory changes, principles of donor selection, and recommended laboratory screening practices for fecal microbiota transplantation.

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