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Faecal Microbiota Transfer in Irritable Bowel Syndrome and Collagenous Colitis: Clinical outcomes and host-microbe interactions
Örebro University, School of Medical Sciences.ORCID iD: 0000-0002-4204-6811
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 [en]
Faecal microbiota transfer, irritable bowel syndrome, collagenous colitis, gut microbiota, visceral sensitivity, host-microbe interactions, gene expression, metabolites
National Category
General Practice
Identifiers
URN: urn:nbn:se:oru:diva-77633ISBN: 978-91-7529-316-5 (print)OAI: oai:DiVA.org:oru-77633DiVA, id: diva2:1366015
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
List of papers
1. The Effect of Allogenic Versus Autologous Fecal Microbiota Transfer on Symptoms, Visceral Perception and Fecal and Mucosal Microbiota in Irritable Bowel Syndrome: A Randomized Controlled Study
Open this publication in new window or tab >>The Effect of Allogenic Versus Autologous Fecal Microbiota Transfer on Symptoms, Visceral Perception and Fecal and Mucosal Microbiota in Irritable Bowel Syndrome: A Randomized Controlled Study
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2019 (English)In: Clinical and Translational Gastroenterology, ISSN 2155-384X, E-ISSN 2155-384X, Vol. 10, no 4, article id e00034Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Fecal microbiota transfer (FMT) is suggested as a potential treatment for patients with irritable bowel syndrome (IBS). We aimed to study the effect of allogenic and autologous FMT on IBS symptoms, visceral sensitivity, and compositional changes in fecal and mucosa-adherent microbiota.

METHODS: Seventeen patients with IBS were randomized either to receive fecal material from a healthy donor (allogenic) or to receive their own fecal material (autologous). The fecal material was administered into the cecum by whole colonoscopy after bowel cleansing.

RESULTS: No significant differences were found between the allogenic and the autologous FMT regarding symptom scores. However, symptom scores of patients receiving allogenic fecal material significantly decreased after FMT compared with baseline (P 5 0.02), which was not the case in the autologous group (P50.16). Visceral sensitivity was not affected except for a small beneficial effect on urge scores in the autologous group (P < 0.05). While both fecal and mucosa-adherent microbiota of some patients shifted to their respective donor’s fecal microbiota, some patients showed no relevant microbial changes after allogenic FMT. Large compositional shifts in fecal and mucosa-adherent microbiota also occurred in the autologous group.

CONCLUSIONS: This study showed that a single FMT by colonoscopy may have beneficial effects in IBS; however, the allogenic fecal material was not superior to the autologous fecal material. This suggests that bowel cleansing prior to the colonoscopy and/or processing of the fecal material as part of the FMT routine contribute to symptoms and gut microbiota composition changes in IBS.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Gastroenterology and Hepatology
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-74035 (URN)10.14309/ctg.0000000000000034 (DOI)000466787000001 ()31009405 (PubMedID)
Funder
Swedish Nutrition Foundation (SNF)
Note

Funding Agencies:

SIAM Gravitation Grant  024.002.002 

Spinoza 2008 Award of the Netherlands Organization for Scientific Research (NWO) 

Available from: 2019-05-06 Created: 2019-05-06 Last updated: 2019-12-20Bibliographically approved
2. Allogenic Faecal Microbiota Transfer Induces Immune-Related Gene Sets in the Colon Mucosa of Patients with Irritable Bowel Syndrome
Open this publication in new window or tab >>Allogenic Faecal Microbiota Transfer Induces Immune-Related Gene Sets in the Colon Mucosa of Patients with Irritable Bowel Syndrome
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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
Keywords
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:nbn:se:oru:diva-77171 (URN)10.3390/biom9100586 (DOI)000497726800078 ()31597320 (PubMedID)2-s2.0-85073107066 (Scopus ID)
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
3. Faecal microbiota transfer in irritable bowel syndrome results inaltered correlations between the gut microbiota and its metabolites
Open this publication in new window or tab >>Faecal microbiota transfer in irritable bowel syndrome results inaltered correlations between the gut microbiota and its metabolites
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-78657 (URN)
Available from: 2019-12-16 Created: 2019-12-16 Last updated: 2019-12-20Bibliographically approved
4. Faecal microbiota transfer in patients with microscopic colitis: A proof-of-concept study in collagenous colitis
Open this publication in new window or tab >>Faecal microbiota transfer in patients with microscopic colitis: A proof-of-concept study in collagenous colitis
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-78659 (URN)
Available from: 2019-12-16 Created: 2019-12-16 Last updated: 2019-12-16Bibliographically approved

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