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 Inter-individual Recovery of the Microbiota and Metabolome Over Time Following Fecal Microbiota Transplantation in Patients with RecurrentClostridium difficileInfection

2017 ◽  
Author(s):  
Anna M. Seekatz ◽  
Casey M. Theriot ◽  
Krishna Rao ◽  
Yu-Ming Chang ◽  
Alison E. Freeman ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Fecal Microbiota Transplantation ◽  
Significant Proportion ◽  
Short Chain Fatty Acids ◽  
Treatment Method ◽  
Gastrointestinal Diseases ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Secondary Bile Acid ◽  
Over Time

ABSTRACTA significant proportion of individuals develop recurrentClostridium difficileinfection (CDI) following initial disease. Fecal microbiota transplantation (FMT), a highly effective treatment method for recurrent CDI, has been demonstrated to induce microbiota recovery, a critical component of disease recovery. However, identification of the specific microbes and their functions that directly impact recovery from CDI remains difficult. We assessed for associations among microbial community members and metabolites in patients with recurrent CDI following treatment with FMT over time to identify groups of bacteria with potential restorative functions. Using 16S rRNA gene-based sequencing, we observed marked similarity of the microbiota between recipients following FMT (n = 6, sampling up to 6 months post-FMT) and their respective donors. Increased levels of the secondary bile acid deoxycholic acid and the short chain fatty acids (SCFAs) butyrate, acetate, and propionate were observed post-FMT. To take into account longitudinal sampling and intra-individual differences, we applied a generalized estimating equation approach to model metabolite concentrations with the presence of specific members of the microbiota. Microbial metabolites that were increased following FMT associated with members classified within theLachnospiraceae, Ruminococcaceae, and unclassifiedClostridialesfamilies. In contrast, members of these taxa were inversely associated with primary bile acids. The longitudinal aspect of this study allowed us to characterize individualized patterns of recovery, revealing variability between and within patients following FMT.IMPORTANCEClostridium difficileinfection (CDI) is an urgent and serious healthcare-associated problem. In recent years, fecal microbiota transplantation (FMT) has been successfully used to treat recurrent CDI, a frequent outcome of disease. While it is apparent that FMT promotes recovery of the microbiota, it is unclear how microbes and their functions promote recovery from disease. This study aimed to identify associations among microbes and metabolites following FMT and to identify critical microbial functions following FMT treatment for recurrent CDI. Overall, recovery of the metabolome was highly dynamic and individualized in all patients, who were all successfully treated. Our results suggest that microbial changes following FMT may be highly specific to the donor-recipient relationship. Further understanding of the host-microbe environments necessary to enable successful transplantation of microbes during FMT could aid development of specific microbial therapeutics for recurrent CDI and other gastrointestinal diseases.

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

2017 ◽  
Vol 55 (4) ◽  
pp. 1002-1010 ◽  
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.

Sign in / Sign up

Export Citation Format

Share Document