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

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
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.

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

mBio ◽  
2016 ◽  
Vol 7 (6) ◽  
Author(s):  
Christopher Staley ◽  
Colleen R. Kelly ◽  
Lawrence J. Brandt ◽  
Alexander Khoruts ◽  
Michael J. Sadowsky
Keyword(s):  
Clostridium Difficile ◽  
Bacterial Communities ◽  
Healthy Donor ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Mean Value ◽  
Bile Acid Metabolism ◽  
Secondary Bile Acid ◽  
Stool Samples ◽  
Relative Abundances

ABSTRACT 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.

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

2020 ◽  
Vol 33 (02) ◽  
pp. 092-097 ◽  
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.

scholarly journals Environmental Contamination in Households of Patients with Recurrent Clostridium difficile Infection

2016 ◽  
Vol 82 (9) ◽  
pp. 2686-2692 ◽  
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.

scholarly journals Recovery of the Gut Microbiome following Fecal Microbiota Transplantation

mBio ◽  
2014 ◽  
Vol 5 (3) ◽  
Author(s):  
Anna M. Seekatz ◽  
Johannes Aas ◽  
Charles E. Gessert ◽  
Timothy A. Rubin ◽  
Daniel M. Saman ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Antibiotic Therapy ◽  
Bacterial Infections ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Transport Systems ◽  
Colonization Resistance ◽  
Treatment Methods ◽  
Content Type ◽  
Functional Changes

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.

scholarly journals Long-Term Bacterial and Fungal Dynamics following Oral Lyophilized Fecal Microbiota Transplantation in Clostridioides difficile Infection

mSystems ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Craig Haifer ◽  
Sudarshan Paramsothy ◽  
Thomas J. Borody ◽  
Annabel Clancy ◽  
Rupert W. Leong ◽  
...  
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Bacterial Species ◽  
Fecal Microbiota ◽  
Fungal Species ◽  
Health Concern ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Gut Colonization ◽  
The Impact

ABSTRACT Oral lyophilized fecal microbiota transplantation (FMT) is effective in recurrent Clostridioides difficile infection (CDI); however, limited data exist on its efficacy in primary CDI and long-term microbial engraftment. Patients with primary or recurrent CDI were prospectively enrolled to receive oral FMT. Changes in the bacterial and fungal communities were characterized prior to and up to 6 months following treatment. A total of 37 patients with CDI (15 primary, 22 recurrent) were treated with 6 capsules each containing 0.35-g lyophilized stool extract. A total of 33 patients (89%) had sustained CDI cure, of whom 3 required a second course. There were no safety signals identified. FMT significantly increased bacterial diversity and shifted composition toward donor profiles in responders but not in nonresponders, with robust donor contribution observed to 6 months following FMT (P < 0.001). Responders showed consistent decreases in Enterobacteriaceae and increases in Faecalibacterium sp. to levels seen in donors. Mycobiome profiling revealed an association with FMT failure and increases in one Penicillium taxon, as well as coexclusion relationships between Candida sp. and bacterial taxa enriched in both donors and responders. Primary CDI was associated with more robust changes in the bacterial community than those with recurrent disease. Oral FMT leads to durable microbial engraftment in patients with primary and recurrent CDI, with several microbial taxa being associated with therapy outcome. Novel coexclusion relationships between bacterial and fungal species support the clinical relevance of transkingdom dynamics. IMPORTANCE Clostridioides difficile infection (CDI) is a substantial health concern worldwide, complicated by patterns of increasing antibiotic resistance that may impact primary treatment. Orally administered fecal microbiota transplantation (FMT) is efficacious in the management of recurrent CDI, with specific bacterial species known to influence clinical outcomes. To date, little is known about the efficacy of FMT in primary CDI and the impact of the mycobiome on therapeutic outcomes. We performed matched bacterial and fungal sequencing on longitudinal samples from a cohort of patients treated with oral FMT for primary and recurrent CDI. We validated many bacterial signatures following oral therapy, confirmed engraftment of donor microbiome out to 6 months following therapy, and demonstrated coexclusion relationships between Candida albicans and two bacterial species in the gut microbiota, which has potential significance beyond CDI, including in the control of gut colonization by this fungal species.

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