Microbial determinants of effective donors in faecal microbiota transplantation for UC.

Haifer, C; Luu, LDW; Paramsothy, S; Borody, TJ; Leong, RW; Kaakoush, NO

Microbial determinants of effective donors in faecal microbiota transplantation for UC.

Haifer, C Luu, LDW Paramsothy, S Borody, TJ Leong, RW Kaakoush, NO

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Publisher:: BMJ Publishing Group
Publication Type:: Journal Article
Citation:: Gut, 2023, 72, (1), pp. 90-100
Issue Date:: 2023-07-25

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Field	Value	Language
dc.contributor.author	Haifer, C
dc.contributor.author	Luu, LDW
dc.contributor.author	Paramsothy, S
dc.contributor.author	Borody, TJ
dc.contributor.author	Leong, RW
dc.contributor.author	Kaakoush, NO
dc.date.accessioned	2024-03-27T01:06:04Z
dc.date.available	2022-07-13
dc.date.available	2024-03-27T01:06:04Z
dc.date.issued	2023-07-25
dc.identifier.citation	Gut, 2023, 72, (1), pp. 90-100
dc.identifier.issn	0017-5749
dc.identifier.issn	1468-3288
dc.identifier.uri	http://hdl.handle.net/10453/177210
dc.description.abstract	OBJECTIVE: Faecal microbiota transplantation (FMT) has variable efficacy in treating UC. Recently, oral lyophilised FMT was found to induce remission in patients with UC, with one donor having 100% efficacy compared with a second donor (36% efficacy). We characterised differences in the gut microbiota of these two donors with the aim of improving FMT donor selection. DESIGN: Faecal samples from the two donors were collected over a period of 44 (donor 1) or 70 (donor 2) weeks. The microbiome and metabolome were profiled using shotgun metagenomics and untargeted metabolomics RESULTS: Gut microbiome long-term stability was highly evident in the effective donor. Donor microbiota species evenness was a robust feature associated with clinical efficacy across two clinical trials of FMT in UC, leading to increased donor species engraftment in patients. Alpha diversity and beta diversity of donor gut microbiotas significantly differed. 90 bacterial species and one archaeon were differentially abundant between donors, 44 of which were >0.1% in relative abundance. 17/44 species were enriched in the effective donor, 11 of which (64.7%) were assembled into high-quality genomes that were prevalent (≥75% samples) in that donor, and six showed evidence of engraftment in patients. Taxonomic differences between donors translated to substantial microbial functional differences that were validated using metabolomics. CONCLUSION: Donor microbiota stability and species evenness were identified as novel metrics that were associated with therapeutic efficacy in UC, beyond individual microbial species or metabolites. These metrics may represent community resilience that translates to better engraftment in the host. TRIAL REGISTRATION NUMBER: ACTRN12619000611123.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	BMJ Publishing Group
dc.relation.ispartof	Gut
dc.relation.isbasedon	10.1136/gutjnl-2022-327742
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1103 Clinical Sciences, 1114 Paediatrics and Reproductive Medicine
dc.subject.classification	Gastroenterology & Hepatology
dc.subject.classification	3202 Clinical sciences
dc.subject.classification	3210 Nutrition and dietetics
dc.title	Microbial determinants of effective donors in faecal microbiota transplantation for UC.
dc.type	Journal Article
utslib.citation.volume	72
utslib.location.activity	England
utslib.for	1103 Clinical Sciences
utslib.for	1114 Paediatrics and Reproductive Medicine
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access	*
pubs.consider-herdc	false
dc.date.updated	2024-03-27T01:06:02Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	72
utslib.citation.issue	1

Abstract:

OBJECTIVE: Faecal microbiota transplantation (FMT) has variable efficacy in treating UC. Recently, oral lyophilised FMT was found to induce remission in patients with UC, with one donor having 100% efficacy compared with a second donor (36% efficacy). We characterised differences in the gut microbiota of these two donors with the aim of improving FMT donor selection. DESIGN: Faecal samples from the two donors were collected over a period of 44 (donor 1) or 70 (donor 2) weeks. The microbiome and metabolome were profiled using shotgun metagenomics and untargeted metabolomics RESULTS: Gut microbiome long-term stability was highly evident in the effective donor. Donor microbiota species evenness was a robust feature associated with clinical efficacy across two clinical trials of FMT in UC, leading to increased donor species engraftment in patients. Alpha diversity and beta diversity of donor gut microbiotas significantly differed. 90 bacterial species and one archaeon were differentially abundant between donors, 44 of which were >0.1% in relative abundance. 17/44 species were enriched in the effective donor, 11 of which (64.7%) were assembled into high-quality genomes that were prevalent (≥75% samples) in that donor, and six showed evidence of engraftment in patients. Taxonomic differences between donors translated to substantial microbial functional differences that were validated using metabolomics. CONCLUSION: Donor microbiota stability and species evenness were identified as novel metrics that were associated with therapeutic efficacy in UC, beyond individual microbial species or metabolites. These metrics may represent community resilience that translates to better engraftment in the host. TRIAL REGISTRATION NUMBER: ACTRN12619000611123.

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http://hdl.handle.net/10453/177210