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Gut microbiota
Original research
Microbial determinants of effective donors in faecal microbiota transplantation for UC
  1. Craig Haifer1,2,3,
  2. Laurence Don Wai Luu4,
  3. Sudarshan Paramsothy1,2,
  4. Thomas J Borody5,
  5. Rupert W Leong1,2,
  6. Nadeem O Kaakoush4
  1. 1 Concord Clinical School, University of Sydney, Sydney, NSW, Australia
  2. 2 Department of Gastroenterology, Concord Repatriation General Hospital, Sydney, NSW, Australia
  3. 3 Department of Gastroenterology, St Vincent's Hospital, Sydney, NSW, Australia
  4. 4 School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia
  5. 5 Centre for Digestive Diseases, Sydney, NSW, Australia
  1. Correspondence to A/Prof Nadeem O Kaakoush, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia; n.kaakoush{at}unsw.edu.au

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.

  • ULCERATIVE COLITIS
  • COLONIC MICROFLORA
  • IBD

Data availability statement

Data are available in a public, open access repository. The raw shotgun metagenomics reads, and the associated metagenomic-assembled genomes were submitted to the European Nucleotide Archive (ENA) under the accession PRJEB50699. 16S rRNA gene amplicon reads are publicly available in ENA under the accession PRJEB48134.

https://doi.org/10.1136/gutjnl-2022-327742

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    Data availability statement

    Data are available in a public, open access repository. The raw shotgun metagenomics reads, and the associated metagenomic-assembled genomes were submitted to the European Nucleotide Archive (ENA) under the accession PRJEB50699. 16S rRNA gene amplicon reads are publicly available in ENA under the accession PRJEB48134.

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    Footnotes

    • CH and LDWL are joint first authors.

    • Twitter @LaurenceLuu, @rupertleong, @NOKaakoush

    • CH and LDWL contributed equally.

    • Contributors Conceptualisation: NOK, RWL, CH, SP and TJB; data curation: LDWL and NOK. formal analysis: NOK and LDWL. Funding acquisition: RWL, NOK, SP, CH and TJB; investigation: CH, LDWL, SP, RWL and NOK; supervision: NOK, RWL and SP; visualisation: NOK; writing (original draft): NOK; writing (review and editing): CH, LDWL, SP, TJB and RWL; guarantor: NOK.

    • Funding The study was funded by The Gutsy Group (2020-2021), St Vincent’s Clinic Foundation (2019), the Gastroenterological Society of Australia (2019, 2020) and an NHMRC Ideas grant (2011047). CH is supported by a research entry scholarship through the Royal Australasian College of Physicians. SP is supported by an NHMRC investigator grant. NOK is supported by a UNSW Scientia fellowship.

    • Competing interests CH reports speaker fees and educational support from Janssen, Pfizer, Takeda, Ferring, Sandoz and Abbvie. SP has served as a consultant for Finch Therapeutics and has received speaker fees from Ferring, Janssen and Takeda. TJB has a pecuniary interest in the Centre for Digestive Diseases, is a medical advisor to Finch Therapeutics, RedHill Bio and Topelia Aust, and holds patents in FMT treatment. RWL reports personal fees from AbbVie, Aspen, Ferring, Celgene, Dr Falk Pharma, Novartis, MSD, Chiesi, BMS and Glutagen; grants and personal fees from Hospira/Pfizer, Janssen and Takeda; grants from Shire Dr Falk Pharma, outside the submitted work. All other authors have no conflicts of interest to declare.

    • Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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