Durable Long-Term Bacterial Engraftment following Encapsulated Fecal Microbiota Transplantation To Treat <named-content content-type="genus-species">Clostridium difficile</named-content> Infection

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...

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Autores principales:	Christopher Staley, Thomas Kaiser, Byron P. Vaughn, Carolyn Graiziger, Matthew J. Hamilton, Amanda J. Kabage, Alexander Khoruts, Michael J. Sadowsky
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Bacteroides capsule FMT donor engraftment fecal transplant stable Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ec3e8108edad4af58a38fec039f6a511
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spelling	oai:doaj.org-article:ec3e8108edad4af58a38fec039f6a5112021-11-15T16:22:11ZDurable Long-Term Bacterial Engraftment following Encapsulated Fecal Microbiota Transplantation To Treat <named-content content-type="genus-species">Clostridium difficile</named-content> Infection10.1128/mBio.01586-192150-7511https://doaj.org/article/ec3e8108edad4af58a38fec039f6a5112019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01586-19https://doaj.org/toc/2150-7511ABSTRACT 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.Christopher StaleyThomas KaiserByron P. VaughnCarolyn GraizigerMatthew J. HamiltonAmanda J. KabageAlexander KhorutsMichael J. SadowskyAmerican Society for MicrobiologyarticleBacteroidescapsule FMTdonorengraftmentfecal transplantstableMicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bacteroides capsule FMT donor engraftment fecal transplant stable Microbiology QR1-502
spellingShingle	Bacteroides capsule FMT donor engraftment fecal transplant stable Microbiology QR1-502 Christopher Staley Thomas Kaiser Byron P. Vaughn Carolyn Graiziger Matthew J. Hamilton Amanda J. Kabage Alexander Khoruts Michael J. Sadowsky Durable Long-Term Bacterial Engraftment following Encapsulated Fecal Microbiota Transplantation To Treat <named-content content-type="genus-species">Clostridium difficile</named-content> Infection
description	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.
format	article
author	Christopher Staley Thomas Kaiser Byron P. Vaughn Carolyn Graiziger Matthew J. Hamilton Amanda J. Kabage Alexander Khoruts Michael J. Sadowsky
author_facet	Christopher Staley Thomas Kaiser Byron P. Vaughn Carolyn Graiziger Matthew J. Hamilton Amanda J. Kabage Alexander Khoruts Michael J. Sadowsky
author_sort	Christopher Staley
title	Durable Long-Term Bacterial Engraftment following Encapsulated Fecal Microbiota Transplantation To Treat <named-content content-type="genus-species">Clostridium difficile</named-content> Infection
title_short	Durable Long-Term Bacterial Engraftment following Encapsulated Fecal Microbiota Transplantation To Treat <named-content content-type="genus-species">Clostridium difficile</named-content> Infection
title_full	Durable Long-Term Bacterial Engraftment following Encapsulated Fecal Microbiota Transplantation To Treat <named-content content-type="genus-species">Clostridium difficile</named-content> Infection
title_fullStr	Durable Long-Term Bacterial Engraftment following Encapsulated Fecal Microbiota Transplantation To Treat <named-content content-type="genus-species">Clostridium difficile</named-content> Infection
title_full_unstemmed	Durable Long-Term Bacterial Engraftment following Encapsulated Fecal Microbiota Transplantation To Treat <named-content content-type="genus-species">Clostridium difficile</named-content> Infection
title_sort	durable long-term bacterial engraftment following encapsulated fecal microbiota transplantation to treat <named-content content-type="genus-species">clostridium difficile</named-content> infection
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/ec3e8108edad4af58a38fec039f6a511
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Durable Long-Term Bacterial Engraftment following Encapsulated Fecal Microbiota Transplantation To Treat <named-content content-type="genus-species">Clostridium difficile</named-content> Infection

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