Virome drift in ulcerative colitis patients: faecal microbiota transplantation results in minimal phage engraftment dominated by microviruses

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent colonic inflammation. Standard treatments focus on controlling inflammation but remain ineffective for one-third of patients. This underscores the need for alternative approaches, such as fecal microbiota transplanta...

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Main Authors: Daan Jansen, Sara Deleu, Clara Caenepeel, Tine Marcelis, Ceren Simsek, Gwen Falony, Kathleen Machiels, João Sabino, Jeroen Raes, Séverine Vermeire, Jelle Matthijnssens
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Gut Microbes
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Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2025.2499575
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author Daan Jansen
Sara Deleu
Clara Caenepeel
Tine Marcelis
Ceren Simsek
Gwen Falony
Kathleen Machiels
João Sabino
Jeroen Raes
Séverine Vermeire
Jelle Matthijnssens
author_facet Daan Jansen
Sara Deleu
Clara Caenepeel
Tine Marcelis
Ceren Simsek
Gwen Falony
Kathleen Machiels
João Sabino
Jeroen Raes
Séverine Vermeire
Jelle Matthijnssens
author_sort Daan Jansen
collection DOAJ
description Ulcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent colonic inflammation. Standard treatments focus on controlling inflammation but remain ineffective for one-third of patients. This underscores the need for alternative approaches, such as fecal microbiota transplantation (FMT), which transfers healthy donor microbiota to patients. The role of viruses in this process, however, remains underexplored. To address this, we analyzed the gut virome using metagenomic sequencing of enriched viral particles from 320 longitudinal fecal samples of 44 patients enrolled in the RESTORE-UC FMT trial. Patients were treated with FMTs from healthy donors (allogenic, treatment) or themselves (autologous, control). We found that colonic inflammation, both its presence and location, had a greater impact on the gut virome than FMT itself. In autologous FMT patients, the virome was unstable and showed rapid divergence over time, a phenomenon we termed virome drift. In allogenic FMT patients, the virome temporarily shifted toward the healthy donor, lasting up to 5 weeks and primarily driven by microviruses. Notably, two distinct virome configurations were identified and linked to either healthy donors or patients. In conclusion, inflammation strongly affects the gut virome in UC patients, which may lead to instability and obstruct the engraftment of allogeneic FMT.
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spelling doaj-art-f2c43a2fd9554417a85f4d29e9f1d1362025-08-20T03:10:10ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2499575Virome drift in ulcerative colitis patients: faecal microbiota transplantation results in minimal phage engraftment dominated by microvirusesDaan Jansen0Sara Deleu1Clara Caenepeel2Tine Marcelis3Ceren Simsek4Gwen Falony5Kathleen Machiels6João Sabino7Jeroen Raes8Séverine Vermeire9Jelle Matthijnssens10Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Viral Metagenomics, KU Leuven, Leuven, BelgiumTranslational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, University Hospitals Leuven, Leuven, BelgiumTranslational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, University Hospitals Leuven, Leuven, BelgiumDepartment of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Viral Metagenomics, KU Leuven, Leuven, BelgiumDepartment of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Viral Metagenomics, KU Leuven, Leuven, BelgiumDepartment of Microbiology Immunology and Transplantation, Rega Institute, Laboratory of Molecular Bacteriology, KU Leuven, Leuven, BelgiumTranslational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, University Hospitals Leuven, Leuven, BelgiumTranslational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, University Hospitals Leuven, Leuven, BelgiumDepartment of Microbiology Immunology and Transplantation, Rega Institute, Laboratory of Molecular Bacteriology, KU Leuven, Leuven, BelgiumTranslational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, University Hospitals Leuven, Leuven, BelgiumDepartment of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Viral Metagenomics, KU Leuven, Leuven, BelgiumUlcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent colonic inflammation. Standard treatments focus on controlling inflammation but remain ineffective for one-third of patients. This underscores the need for alternative approaches, such as fecal microbiota transplantation (FMT), which transfers healthy donor microbiota to patients. The role of viruses in this process, however, remains underexplored. To address this, we analyzed the gut virome using metagenomic sequencing of enriched viral particles from 320 longitudinal fecal samples of 44 patients enrolled in the RESTORE-UC FMT trial. Patients were treated with FMTs from healthy donors (allogenic, treatment) or themselves (autologous, control). We found that colonic inflammation, both its presence and location, had a greater impact on the gut virome than FMT itself. In autologous FMT patients, the virome was unstable and showed rapid divergence over time, a phenomenon we termed virome drift. In allogenic FMT patients, the virome temporarily shifted toward the healthy donor, lasting up to 5 weeks and primarily driven by microviruses. Notably, two distinct virome configurations were identified and linked to either healthy donors or patients. In conclusion, inflammation strongly affects the gut virome in UC patients, which may lead to instability and obstruct the engraftment of allogeneic FMT.https://www.tandfonline.com/doi/10.1080/19490976.2025.2499575Ulcerative colitisfecal microbiota transplantsviromevirome driftvirome community types
spellingShingle Daan Jansen
Sara Deleu
Clara Caenepeel
Tine Marcelis
Ceren Simsek
Gwen Falony
Kathleen Machiels
João Sabino
Jeroen Raes
Séverine Vermeire
Jelle Matthijnssens
Virome drift in ulcerative colitis patients: faecal microbiota transplantation results in minimal phage engraftment dominated by microviruses
Gut Microbes
Ulcerative colitis
fecal microbiota transplants
virome
virome drift
virome community types
title Virome drift in ulcerative colitis patients: faecal microbiota transplantation results in minimal phage engraftment dominated by microviruses
title_full Virome drift in ulcerative colitis patients: faecal microbiota transplantation results in minimal phage engraftment dominated by microviruses
title_fullStr Virome drift in ulcerative colitis patients: faecal microbiota transplantation results in minimal phage engraftment dominated by microviruses
title_full_unstemmed Virome drift in ulcerative colitis patients: faecal microbiota transplantation results in minimal phage engraftment dominated by microviruses
title_short Virome drift in ulcerative colitis patients: faecal microbiota transplantation results in minimal phage engraftment dominated by microviruses
title_sort virome drift in ulcerative colitis patients faecal microbiota transplantation results in minimal phage engraftment dominated by microviruses
topic Ulcerative colitis
fecal microbiota transplants
virome
virome drift
virome community types
url https://www.tandfonline.com/doi/10.1080/19490976.2025.2499575
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