Profiling the colonic mucosal response to fecal microbiota transplantation identifies a role for GBP5 in colitis in humans and mice

Abstract Host molecular responses to fecal microbiota transplantation (FMT) in ulcerative colitis are not well understood. Here, we profile the human colonic mucosal transcriptome prior to and following FMT or placebo to identify molecules regulated during disease remission. FMT alters the transcrip...

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Main Authors: Laurence D. W. Luu, Abhimanu Pandey, Sudarshan Paramsothy, Chinh Ngo, Natalia Castaño-Rodríguez, Cheng Liu, Michael A. Kamm, Thomas J. Borody, Si Ming Man, Nadeem O. Kaakoush
Format: Article
Language:English
Published: Nature Portfolio 2024-03-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-46983-5
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author Laurence D. W. Luu
Abhimanu Pandey
Sudarshan Paramsothy
Chinh Ngo
Natalia Castaño-Rodríguez
Cheng Liu
Michael A. Kamm
Thomas J. Borody
Si Ming Man
Nadeem O. Kaakoush
author_facet Laurence D. W. Luu
Abhimanu Pandey
Sudarshan Paramsothy
Chinh Ngo
Natalia Castaño-Rodríguez
Cheng Liu
Michael A. Kamm
Thomas J. Borody
Si Ming Man
Nadeem O. Kaakoush
author_sort Laurence D. W. Luu
collection DOAJ
description Abstract Host molecular responses to fecal microbiota transplantation (FMT) in ulcerative colitis are not well understood. Here, we profile the human colonic mucosal transcriptome prior to and following FMT or placebo to identify molecules regulated during disease remission. FMT alters the transcriptome above the effect of placebo (n = 75 vs 3 genes, q < 0.05), including modulation of structural, metabolic and inflammatory pathways. This response is attributed to responders with no consistency observed in non-responders. Regulated pathways in responders include tight junctions, calcium signalling and xenobiotic metabolism. Genes significantly regulated longitudinally in responders post-FMT could discriminate them from responders and non-responders at baseline and non-responders post-FMT, with GBP5 and IRF4 downregulation being associated with remission. Female mice with a deletion of GBP5 are more resistant to developing colitis than their wild-type littermates, showing higher colonic IRF4 phosphorylation. The colonic mucosal response discriminates UC remission following FMT, with GBP5 playing a detrimental role in colitis.
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spelling doaj.art-8fb4cb1f0049425d9de3a9f287ea6c0f2024-03-31T11:26:07ZengNature PortfolioNature Communications2041-17232024-03-0115111310.1038/s41467-024-46983-5Profiling the colonic mucosal response to fecal microbiota transplantation identifies a role for GBP5 in colitis in humans and miceLaurence D. W. Luu0Abhimanu Pandey1Sudarshan Paramsothy2Chinh Ngo3Natalia Castaño-Rodríguez4Cheng Liu5Michael A. Kamm6Thomas J. Borody7Si Ming Man8Nadeem O. Kaakoush9School of Biomedical Sciences, UNSWThe John Curtin School of Medical Research, The Australian National UniversityConcord Clinical School, The University of SydneyThe John Curtin School of Medical Research, The Australian National UniversitySchool of Biotechnology and Biomolecular Sciences, UNSWConjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research InstituteDepartment of Gastroenterology, St Vincent’s HospitalCentre for Digestive DiseasesThe John Curtin School of Medical Research, The Australian National UniversitySchool of Biomedical Sciences, UNSWAbstract Host molecular responses to fecal microbiota transplantation (FMT) in ulcerative colitis are not well understood. Here, we profile the human colonic mucosal transcriptome prior to and following FMT or placebo to identify molecules regulated during disease remission. FMT alters the transcriptome above the effect of placebo (n = 75 vs 3 genes, q < 0.05), including modulation of structural, metabolic and inflammatory pathways. This response is attributed to responders with no consistency observed in non-responders. Regulated pathways in responders include tight junctions, calcium signalling and xenobiotic metabolism. Genes significantly regulated longitudinally in responders post-FMT could discriminate them from responders and non-responders at baseline and non-responders post-FMT, with GBP5 and IRF4 downregulation being associated with remission. Female mice with a deletion of GBP5 are more resistant to developing colitis than their wild-type littermates, showing higher colonic IRF4 phosphorylation. The colonic mucosal response discriminates UC remission following FMT, with GBP5 playing a detrimental role in colitis.https://doi.org/10.1038/s41467-024-46983-5
spellingShingle Laurence D. W. Luu
Abhimanu Pandey
Sudarshan Paramsothy
Chinh Ngo
Natalia Castaño-Rodríguez
Cheng Liu
Michael A. Kamm
Thomas J. Borody
Si Ming Man
Nadeem O. Kaakoush
Profiling the colonic mucosal response to fecal microbiota transplantation identifies a role for GBP5 in colitis in humans and mice
Nature Communications
title Profiling the colonic mucosal response to fecal microbiota transplantation identifies a role for GBP5 in colitis in humans and mice
title_full Profiling the colonic mucosal response to fecal microbiota transplantation identifies a role for GBP5 in colitis in humans and mice
title_fullStr Profiling the colonic mucosal response to fecal microbiota transplantation identifies a role for GBP5 in colitis in humans and mice
title_full_unstemmed Profiling the colonic mucosal response to fecal microbiota transplantation identifies a role for GBP5 in colitis in humans and mice
title_short Profiling the colonic mucosal response to fecal microbiota transplantation identifies a role for GBP5 in colitis in humans and mice
title_sort profiling the colonic mucosal response to fecal microbiota transplantation identifies a role for gbp5 in colitis in humans and mice
url https://doi.org/10.1038/s41467-024-46983-5
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