Transferable Immunoglobulin A-Coated Odoribacter splanchnicus in Responders to Fecal Microbiota Transplantation for Ulcerative Colitis Limits Colonic Inflammation.
Animals
Bacteroidetes
/ genetics
Clinical Trials as Topic
Colitis
/ immunology
Colitis, Ulcerative
/ diagnosis
Colon
/ immunology
Disease Models, Animal
Fecal Microbiota Transplantation
Forkhead Transcription Factors
/ metabolism
Gastrointestinal Microbiome
/ genetics
Germ-Free Life
Humans
Immunity, Mucosal
Immunoglobulin A
/ genetics
Intestinal Mucosa
/ immunology
Intraepithelial Lymphocytes
/ immunology
Metagenome
Metagenomics
Mice, Inbred C57BL
Mice, Knockout
Nuclear Receptor Subfamily 1, Group F, Member 3
/ metabolism
T-Lymphocytes, Regulatory
/ immunology
Treatment Outcome
Fecal Microbiota Transplant
IgA-Seq
Odoribacter
Ulcerative Colitis
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
21
04
2021
revised:
01
09
2021
accepted:
28
09
2021
pubmed:
5
10
2021
medline:
19
1
2022
entrez:
4
10
2021
Statut:
ppublish
Résumé
Fecal microbiota transplantation (FMT) is an emerging treatment modality for ulcerative colitis (UC). Several randomized controlled trials have shown efficacy for FMT in the treatment of UC, but a better understanding of the transferable microbiota and their immune impact is needed to develop more efficient microbiome-based therapies for UC. Metagenomic analysis and strain tracking was performed on 60 donor and recipient samples receiving FMT for active UC. Sorting and sequencing of immunoglobulin (Ig) A-coated microbiota (called IgA-seq) was used to define immune-reactive microbiota. Colonization of germ-free or genetically engineered mice with patient-derived strains was performed to determine the mechanism of microbial impact on intestinal immunity. Metagenomic analysis defined a core set of donor-derived transferable bacterial strains in UC subjects achieving clinical response, which predicted response in an independent trial of FMT for UC. IgA-seq of FMT recipient samples and gnotobiotic mice colonized with donor microbiota identified Odoribacter splanchnicus as a transferable strain shaping mucosal immunity, which correlated with clinical response and the induction of mucosal regulatory T cells. Colonization of mice with O splanchnicus led to an increase in Foxp3 This work provides the first evidence of transferable, donor-derived strains that correlate with clinical response to FMT in UC and reveals O splanchnicus as a key component promoting both metabolic and immune cell protection from colitis. These mechanistic features will help enable strategies to enhance the efficacy of microbial therapy for UC. Clinicaltrials.gov ID NCT02516384.
Sections du résumé
BACKGROUND & AIMS
Fecal microbiota transplantation (FMT) is an emerging treatment modality for ulcerative colitis (UC). Several randomized controlled trials have shown efficacy for FMT in the treatment of UC, but a better understanding of the transferable microbiota and their immune impact is needed to develop more efficient microbiome-based therapies for UC.
METHODS
Metagenomic analysis and strain tracking was performed on 60 donor and recipient samples receiving FMT for active UC. Sorting and sequencing of immunoglobulin (Ig) A-coated microbiota (called IgA-seq) was used to define immune-reactive microbiota. Colonization of germ-free or genetically engineered mice with patient-derived strains was performed to determine the mechanism of microbial impact on intestinal immunity.
RESULTS
Metagenomic analysis defined a core set of donor-derived transferable bacterial strains in UC subjects achieving clinical response, which predicted response in an independent trial of FMT for UC. IgA-seq of FMT recipient samples and gnotobiotic mice colonized with donor microbiota identified Odoribacter splanchnicus as a transferable strain shaping mucosal immunity, which correlated with clinical response and the induction of mucosal regulatory T cells. Colonization of mice with O splanchnicus led to an increase in Foxp3
CONCLUSIONS
This work provides the first evidence of transferable, donor-derived strains that correlate with clinical response to FMT in UC and reveals O splanchnicus as a key component promoting both metabolic and immune cell protection from colitis. These mechanistic features will help enable strategies to enhance the efficacy of microbial therapy for UC. Clinicaltrials.gov ID NCT02516384.
Identifiants
pubmed: 34606847
pii: S0016-5085(21)03610-6
doi: 10.1053/j.gastro.2021.09.061
pmc: PMC8678328
mid: NIHMS1745361
pii:
doi:
Substances chimiques
Forkhead Transcription Factors
0
Foxp3 protein, mouse
0
Immunoglobulin A
0
Nuclear Receptor Subfamily 1, Group F, Member 3
0
Rorc protein, mouse
0
Banques de données
ClinicalTrials.gov
['NCT02516384']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
166-178Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK114252
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK120985
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK128257
Pays : United States
Informations de copyright
Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.
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