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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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2021-02-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-84152-6
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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
collection DOAJ
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.
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spelling doaj.art-ada7bfb87fa644a88ca2f400ae09159f2022-12-21T21:27:12ZengNature PortfolioScientific Reports2045-23222021-02-011111910.1038/s41598-021-84152-6Lower endoscopic delivery of freeze-dried intestinal microbiota results in more rapid and efficient engraftment than oral administrationChristopher Staley0Hossam Halaweish1Carolyn Graiziger2Matthew J. Hamilton3Amanda J. Kabage4Alison L. Galdys5Byron P. Vaughn6Kornpong Vantanasiri7Raj Suryanarayanan8Michael J. Sadowsky9Alexander Khoruts10Division of Basic & Translational Research, Department of Surgery, University of MinnesotaDivision of Basic & Translational Research, Department of Surgery, University of MinnesotaDivision of Gastroenterology, Department of Medicine, University of MinnesotaBioTechnology Institute, University of MinnesotaDivision of Gastroenterology, Department of Medicine, University of MinnesotaDivision of Infectious Diseases and International Medicine, Department of Medicine, University of MinnesotaDivision of Gastroenterology, Department of Medicine, University of MinnesotaDivision of Gastroenterology, Department of Medicine, University of MinnesotaDepartment of Pharmaceutics, College of Pharmacy, University of MinnesotaBioTechnology Institute, University of MinnesotaBioTechnology Institute, University of MinnesotaAbstract 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.https://doi.org/10.1038/s41598-021-84152-6
spellingShingle 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
Scientific Reports
title 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_short 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
url https://doi.org/10.1038/s41598-021-84152-6
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