Lower endoscopic delivery of freeze-dried intestinal microbiota results in more rapid and efficient engraftment than oral administration

Abstract Fecal microbiota transplantation (FMT) is a highly effective treatment for recurrent Clostridioides difficile infection (rCDI). However, standardization of FMT products is essential for its broad implementation into clinical practice. We have developed an oral preparation of freeze-dried, e...

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Autores principales: Christopher Staley, Hossam Halaweish, Carolyn Graiziger, Matthew J. Hamilton, Amanda J. Kabage, Alison L. Galdys, Byron P. Vaughn, Kornpong Vantanasiri, Raj Suryanarayanan, Michael J. Sadowsky, Alexander Khoruts
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:ada7bfb87fa644a88ca2f400ae09159f2021-12-02T13:34:57ZLower endoscopic delivery of freeze-dried intestinal microbiota results in more rapid and efficient engraftment than oral administration10.1038/s41598-021-84152-62045-2322https://doaj.org/article/ada7bfb87fa644a88ca2f400ae09159f2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84152-6https://doaj.org/toc/2045-2322Abstract Fecal microbiota transplantation (FMT) is a highly effective treatment for recurrent Clostridioides difficile infection (rCDI). However, standardization of FMT products is essential for its broad implementation into clinical practice. We have developed an oral preparation of freeze-dried, encapsulated microbiota, which is ~ 80% clinically effective, but results in delayed engraftment of donor bacteria relative to administration via colonoscopy. Our objective was to measure the engraftment potential of freeze-dried microbiota without the complexity of variables associated with oral administration. We compared engraftment of identical preparations and doses of freeze-dried microbiota following colonoscopic (9 patients) versus oral administration (18 patients). Microbiota were characterized by sequencing of the 16S rRNA gene, and engraftment was determined using the SourceTracker algorithm. Oligotyping analysis was done to provide high-resolution patterns of microbiota engraftment. Colonoscopic FMT was associated with greater levels of donor engraftment within days following the procedure (ANOVA P = 0.035) and specific increases in the relative abundances of donor Lachnospiraceae, Bacteroidaceae, and Porphyromonadaceae (P ≤ 0.033). Lower relative abundances of Bacteroidaceae, Lachnospiraceae, and Ruminococcaceae families were associated with clinical failures. These results suggest that further optimization of oral capsule FMT may improve its engraftment efficiency and clinical efficacy.Christopher StaleyHossam HalaweishCarolyn GraizigerMatthew J. HamiltonAmanda J. KabageAlison L. GaldysByron P. VaughnKornpong VantanasiriRaj SuryanarayananMichael J. SadowskyAlexander KhorutsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Christopher Staley
Hossam Halaweish
Carolyn Graiziger
Matthew J. Hamilton
Amanda J. Kabage
Alison L. Galdys
Byron P. Vaughn
Kornpong Vantanasiri
Raj Suryanarayanan
Michael J. Sadowsky
Alexander Khoruts
Lower endoscopic delivery of freeze-dried intestinal microbiota results in more rapid and efficient engraftment than oral administration
description Abstract Fecal microbiota transplantation (FMT) is a highly effective treatment for recurrent Clostridioides difficile infection (rCDI). However, standardization of FMT products is essential for its broad implementation into clinical practice. We have developed an oral preparation of freeze-dried, encapsulated microbiota, which is ~ 80% clinically effective, but results in delayed engraftment of donor bacteria relative to administration via colonoscopy. Our objective was to measure the engraftment potential of freeze-dried microbiota without the complexity of variables associated with oral administration. We compared engraftment of identical preparations and doses of freeze-dried microbiota following colonoscopic (9 patients) versus oral administration (18 patients). Microbiota were characterized by sequencing of the 16S rRNA gene, and engraftment was determined using the SourceTracker algorithm. Oligotyping analysis was done to provide high-resolution patterns of microbiota engraftment. Colonoscopic FMT was associated with greater levels of donor engraftment within days following the procedure (ANOVA P = 0.035) and specific increases in the relative abundances of donor Lachnospiraceae, Bacteroidaceae, and Porphyromonadaceae (P ≤ 0.033). Lower relative abundances of Bacteroidaceae, Lachnospiraceae, and Ruminococcaceae families were associated with clinical failures. These results suggest that further optimization of oral capsule FMT may improve its engraftment efficiency and clinical efficacy.
format article
author Christopher Staley
Hossam Halaweish
Carolyn Graiziger
Matthew J. Hamilton
Amanda J. Kabage
Alison L. Galdys
Byron P. Vaughn
Kornpong Vantanasiri
Raj Suryanarayanan
Michael J. Sadowsky
Alexander Khoruts
author_facet Christopher Staley
Hossam Halaweish
Carolyn Graiziger
Matthew J. Hamilton
Amanda J. Kabage
Alison L. Galdys
Byron P. Vaughn
Kornpong Vantanasiri
Raj Suryanarayanan
Michael J. Sadowsky
Alexander Khoruts
author_sort Christopher Staley
title Lower endoscopic delivery of freeze-dried intestinal microbiota results in more rapid and efficient engraftment than oral administration
title_short Lower endoscopic delivery of freeze-dried intestinal microbiota results in more rapid and efficient engraftment than oral administration
title_full Lower endoscopic delivery of freeze-dried intestinal microbiota results in more rapid and efficient engraftment than oral administration
title_fullStr Lower endoscopic delivery of freeze-dried intestinal microbiota results in more rapid and efficient engraftment than oral administration
title_full_unstemmed Lower endoscopic delivery of freeze-dried intestinal microbiota results in more rapid and efficient engraftment than oral administration
title_sort lower endoscopic delivery of freeze-dried intestinal microbiota results in more rapid and efficient engraftment than oral administration
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/ada7bfb87fa644a88ca2f400ae09159f
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