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Recent advances in basic science
Translational strategies for oral delivery of faecal microbiota transplantation
  1. Srinivas Kamath1,
  2. Robert V Bryant2,3,
  3. Samuel P Costello2,4,
  4. Alice S Day3,5,
  5. Ben Forbes6,
  6. Craig Haifer7,8,
  7. Georgina Hold9,
  8. Colleen R Kelly10,11,
  9. Anna Li12,
  10. Evance Pakuwal13,
  11. Andrea Stringer1,
  12. Emily C Tucker3,14,
  13. Hannah Rose Wardill12,15,
  14. Paul Joyce16
  1. 1UniSA Clinical & Health Sciences, University of South Australia, Adelaide, South Australia, Australia
  2. 2Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia
  3. 3Faculty of Health Sciences, The University of Adelaide, Adelaide, South Australia, Australia
  4. 4The University of Adelaide, Adelaide, South Australia, Australia
  5. 5Gastroenterology, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia
  6. 6King’s College London, London, UK
  7. 7Department of Gastroenterology, St Vincent’s Hospital Sydney, Darlinghurst, New South Wales, Australia
  8. 8School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia
  9. 9Microbiome Research Centre, University of New South Wales, Sydney, New South Wales, Australia
  10. 10Harvard Medical School, Boston, Massachusetts, USA
  11. 11Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
  12. 12Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia
  13. 13Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia
  14. 14Infectious Diseases Unit, Central Adelaide Local Health Network, Adelaide, South Australia, Australia
  15. 15Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
  16. 16University of South Australia, Adelaide, South Australia, Australia
  1. Correspondence to Dr Paul Joyce; paul.joyce{at}unisa.edu.au

Abstract

Faecal microbiota transplantation (FMT) has emerged as a transformative therapy for Clostridioides difficile infections and shows promise for various GI and systemic diseases. However, the poor patient acceptability and accessibility of ‘conventional’ FMT, typically administered via colonoscopies or enemas, hinders its widespread clinical adoption, particularly for chronic conditions. Oral administration of FMT (OralFMT) overcomes these limitations, yet faces distinct challenges, including a significant capsule burden, palatability concerns and poor microbial viability during gastric transit. This review provides a comprehensive analysis of emerging strategies that aim to advance OralFMT by: (1) refining processing technologies (eg, lyophilisation) that enable manufacturing of low-volume FMT formulations for reducing capsule burden and (2) developing delivery technologies that improve organoleptic acceptability and safeguard the microbiota for targeted colonic release. These advancements present opportunities for OralFMT to expand its therapeutic scope, beyond C. difficile infections, towards chronic GI conditions requiring frequent dosing regimens. While this review primarily focuses on optimising OralFMT delivery, it is important to contextualise these advancements within the broader shift towards defined microbial consortia. Live biotherapeutic products (LBPs) offer an alternative approach, yet the interplay between OralFMT and LBPs in clinical practice remains unresolved. We postulate that continued innovation in OralFMT and LBPs via a multidisciplinary approach can further increase therapeutic efficacy and scalability by enabling disease site targeting, co-delivery of therapeutic compounds and overcoming colonisation resistance. Realising these goals positions OralFMT as a cornerstone of personalised care across a range of diseases rooted in microbiome health.

  • microbiome
  • intestinal transplantation
  • drug development
  • IBD
  • adjuvant treatment

https://doi.org/10.1136/gutjnl-2025-335077

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    Footnotes

    • X @Alice_APD, @hannahrwardill, @Paul_Joyce_

    • Contributors PJ is the guarantor. SK and PJ conceptualised this project, curated the data and performed formal analysis. SK wrote the original draft. RVB, SPC, ASD, BF, CH, GH, CRK, AL, EP, AS, ECT, HRW and PJ reviewed and edited the manuscript. PJ was responsible for funding acquisition and project administration.

    • Funding This study was funded by Hospital Research Foundation (2021-CF-EMCR-007-25313, 2022-CF-EMCR-004-25314).

    • Competing interests RVB, SPC and ECT report conflicts with BiomeBank. HRW and PJ report conflicts with The Hospital Research Foundation Group.

    • 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.