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Allogenic Faecal Microbiota Transfer Induces Immune-Related Gene Sets in the Colon Mucosa of Patients with Irritable Bowel Syndrome
Örebro University, School of Medical Sciences. (NGBI)ORCID iD: 0000-0002-4204-6811
Nutrition, Metabolism and Genomics group, Division of Human Nutrition and Health, Wageningen University, Wageningen, The Netherlands.
Örebro University, School of Medical Sciences. (NGBI)ORCID iD: 0000-0002-7173-5579
Laboratory of Microbiology, Wageningen University and Research Centre and Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
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2019 (English)In: Biomolecules, E-ISSN 2218-273X, Vol. 9, no 10, article id 586Article in journal (Refereed) Published
Abstract [en]

Faecal microbiota transfer (FMT) consists of the introduction of new microbial communities into the intestine of a patient, with the aim of restoring a disturbed gut microbiota. Even though it is used as a potential treatment for various diseases, it is unknown how the host mucosa responds to FMT. This study aims to investigate the colonic mucosa gene expression response to allogenic (from a donor) or autologous (own) FMT in patients with irritable bowel syndrome (IBS). In a recently conducted randomised, double-blinded, controlled clinical study, 17 IBS patients were treated with FMT by colonoscopy. RNA was isolated from colonic biopsies collected by sigmoidoscopy at baseline, as well as two weeks and eight weeks after FMT. In patients treated with allogenic FMT, predominantly immune response-related gene sets were induced, with the strongest response two weeks after the FMT. In patients treated with autologous FMT, predominantly metabolism-related gene sets were affected. Furthermore, several microbiota genera showed correlations with immune-related gene sets, with different correlations found after allogenic compared to autologous FMT. This study shows that the microbe–host response is influenced by FMT on the mucosal gene expression level, and that there are clear differences in response to allogenic compared to autologous FMT.

Place, publisher, year, edition, pages
MDPI, 2019. Vol. 9, no 10, article id 586
Keywords [en]
Faecal microbiota transfer, Faecal microbiota transplantation, irritable bowel syndrome, gene expression, gut microbiota, host-microbe interaction
National Category
Gastroenterology and Hepatology
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-77171DOI: 10.3390/biom9100586ISI: 000497726800078PubMedID: 31597320Scopus ID: 2-s2.0-85073107066OAI: oai:DiVA.org:oru-77171DiVA, id: diva2:1359756
Funder
Knowledge Foundation
Note

Funding Agencies:

European Society of Clinical Nutrition and Metabolism (ESPEN)  

Netherlands Organization for Scientific Research (NWO)

Available from: 2019-10-10 Created: 2019-10-10 Last updated: 2019-12-16Bibliographically approved
In thesis
1. Faecal Microbiota Transfer in Irritable Bowel Syndrome and Collagenous Colitis: Clinical outcomes and host-microbe interactions
Open this publication in new window or tab >>Faecal Microbiota Transfer in Irritable Bowel Syndrome and Collagenous Colitis: Clinical outcomes and host-microbe interactions
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Faecal microbiota transfer (FMT) aims at restoring a disturbed gut microbiotaby introducing faecal material from a healthy donor into a patient’s intestine. This approach is known as a safe and effective treatment in patients with recurrent Clostridioides difficile infection. This thesis describes the outcomes of two clinical studies in which FMT was investigated as a therapy for irritable bowel syndrome (IBS) patients andin collagenous colitis (CC) patients. Paper I showed that there were no significant differences in IBS symptom scores between patients receiving faecal material from a healthy donor (allogenic FMT) and patients receiving their own faecal material back (autologous FMT). However, unlike autologous FMT, allogenic FMT significantly decreased symptom scores compared to baseline. Additionally, allogenic FMT wasshown to alter the faecal as well as the mucosal microbiota of the IBSpatients. However, also the autologous FMT had an effect on the faecal and mucosal microbiota indicating that the bowel cleansing and/or theprocessing of the autologous faecal material affected the gut microbiota. Paper II showed that the allogenic FMT evoked a clearly different host response in IBS patients than the autologous FMT. Paper III showedthat allogenic FMT did not result in altered faecal metabolite profilesbut in disturbed interactions between the gut microbiota and its metabolites compared to autologous FMT. Paper IV describes the outcomes of the second clinical study in which repeated FMTs resulted inless diarrhoea in a subset of the treated CC patients.

Although symptoms improved in both clinical studies, the introduction of a new microbiota by FMT did not seem to be the miracle curefor IBS and CC. However, a subset of patients could benefit from FMT, and a future challenge is to identify this subset. The findings of this thesis are essential for designing further studies aimed at increasing FMT efficacy.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2020. p. 76
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 204
Keywords
Faecal microbiota transfer, irritable bowel syndrome, collagenous colitis, gut microbiota, visceral sensitivity, host-microbe interactions, gene expression, metabolites
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-77633 (URN)978-91-7529-316-5 (ISBN)
Public defence
2020-01-17, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 09:00 (English)
Opponent
Supervisors
Available from: 2019-10-28 Created: 2019-10-28 Last updated: 2019-12-16Bibliographically approved

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Holster, SavanneRepsilber, DirkBrummer, Robert JanKönig, Julia

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