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Holster, S. (2020). Faecal Microbiota Transfer in Irritable Bowel Syndrome and Collagenous Colitis: Clinical outcomes and host-microbe interactions. (Doctoral dissertation). Örebro: Örebro University
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
Holster, S., Hooiveld, G. J., Repsilber, D., de Vos, W., Brummer, R. J. & König, J. (2019). Allogenic Faecal Microbiota Transfer Induces Immune-Related Gene Sets in the Colon Mucosa of Patients with Irritable Bowel Syndrome. Biomolecules, 9(10), Article ID 586.
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
Holster, S., Lindqvist, C. M., Repsilber, D., Salonen, A., de Vos, W., König, J. & Brummer, R. J. (2019). 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. Clinical and Translational Gastroenterology, 10(4), Article ID e00034.
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
König, J., Holster, S., Bruins, M. & Brummer, R. J. (2017). Aspergillus Niger-Derived Enzyme Degrades Gluten in the Stomach of Gluten-Sensitive Subjects. In: 2017 DDW Abstracts: . Paper presented at Digestive Disease Week (DDW), Chicago, IL, USA, May 6-9, 2017 (pp. S481-S481). Saunders Elsevier, 152(5)
Open this publication in new window or tab >>Aspergillus Niger-Derived Enzyme Degrades Gluten in the Stomach of Gluten-Sensitive Subjects
2017 (English)In: 2017 DDW Abstracts, Saunders Elsevier, 2017, Vol. 152, no 5, p. S481-S481Conference paper, Oral presentation with published abstract (Other academic)
Place, publisher, year, edition, pages
Saunders Elsevier, 2017
Series
Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-66299 (URN)10.1016/S0016-5085(17)31796-1 (DOI)000403140302008 ()
Conference
Digestive Disease Week (DDW), Chicago, IL, USA, May 6-9, 2017
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2019-05-06Bibliographically approved
König, J., Holster, S., Bruins, M. & Brummer, R. J. (2017). Effective gluten degradation in non-coeliac gluten-sensitive subjects by Aspergillus Niger derived enzyme: A placebo-controlled randomized clinical trial. In: : . Paper presented at United European Gastroenterology (UEG) Week, Barcelona (Oct 28-Nov 1, 2017) (pp. A28). Sage Publications, 5, Article ID OP065.
Open this publication in new window or tab >>Effective gluten degradation in non-coeliac gluten-sensitive subjects by Aspergillus Niger derived enzyme: A placebo-controlled randomized clinical trial
2017 (English)Conference paper, Oral presentation with published abstract (Refereed)
Place, publisher, year, edition, pages
Sage Publications, 2017
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:oru:diva-66300 (URN)10.1177/2050640617725668 (DOI)
Conference
United European Gastroenterology (UEG) Week, Barcelona (Oct 28-Nov 1, 2017)
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2019-03-26Bibliographically approved
Holster, S., Repsilber, D., Brummer, R. J. & König, J. (2017). Faecal microbiota transfer in irritable bowel syndrome: clinical outcomes of a randomised placebo-controlled trial. In: UEG Week 2017 Oral Presentations: . Paper presented at United European Gastroenterology (UEG) Week, Barcelona, Spain, October 28 - November 1, 2017 (pp. A155-A156). Sage Publications, 5
Open this publication in new window or tab >>Faecal microbiota transfer in irritable bowel syndrome: clinical outcomes of a randomised placebo-controlled trial
2017 (English)In: UEG Week 2017 Oral Presentations, Sage Publications, 2017, Vol. 5, p. A155-A156Conference paper, Oral presentation with published abstract (Refereed)
Place, publisher, year, edition, pages
Sage Publications, 2017
Series
United European Gastroenterology Journal, ISSN 2050-6406, E-ISSN 2050-6414
National Category
Gastroenterology and Hepatology
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-66283 (URN)10.1177/2050640617725668 (DOI)
Conference
United European Gastroenterology (UEG) Week, Barcelona, Spain, October 28 - November 1, 2017
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2019-10-18Bibliographically approved
Holster, S., Brummer, R. J., Repsilber, D. & König, J. (2017). Fecal Microbiota Transplantation in Irritable Bowel Syndrome and a Randomized Placebo-Controlled Trial. In: 2017 DDW Abstracts: . Paper presented at Digestive Disease Week (DDW), Chicago, IL, USA, May 6-9, 2017 (pp. S101-S102). Saunders Elsevier, 152(5)
Open this publication in new window or tab >>Fecal Microbiota Transplantation in Irritable Bowel Syndrome and a Randomized Placebo-Controlled Trial
2017 (English)In: 2017 DDW Abstracts, Saunders Elsevier, 2017, Vol. 152, no 5, p. S101-S102Conference paper, Oral presentation with published abstract (Other academic)
Place, publisher, year, edition, pages
Saunders Elsevier, 2017
Series
Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-66294 (URN)10.1016/S0016-5085(17)30679-0 (DOI)000403140300297 ()
Conference
Digestive Disease Week (DDW), Chicago, IL, USA, May 6-9, 2017
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2019-05-06Bibliographically approved
König, J., Holster, S., Maaike, B. & Brummer, R. J. (2017). Randomized clinical trial: Effective gluten degradation by Aspergillus niger-derived enzyme in a complex meal setting. Scientific Reports, 7(13100)
Open this publication in new window or tab >>Randomized clinical trial: Effective gluten degradation by Aspergillus niger-derived enzyme in a complex meal setting
2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, no 13100Article in journal (Refereed) Published
Abstract [en]

The Aspergillus niger-derived prolyl endoprotease (AN-PEP) has previously been shown to degrade gluten in healthy subjects when added to an intragastrically infused meal. The current study investigated the efficacy of AN-PEP in a physiological meal setting. In this randomized placebo-controlled crossover study, 18 gluten-sensitive subjects consumed a porridge containing 0.5 g gluten together with two tablets either containing a high or low dose of AN-PEP, or placebo. Gastric and duodenal content was sampled over 180 minutes, and areas under the curve of gluten concentrations were calculated. The primary outcome, i.e. success rate of high dose AN-PEP defined as at least 50% gluten degradation compared to placebo in the duodenum, was achieved in 10 of 13 comparisons. In the stomach, gluten levels were reduced from 176.9 (median, interquartile range 73.5–357.8) to 22.0 (10.6–50.8, p = 0.001) in the high dose and to 25.4 μg × min/ml (16.4–43.7, p = 0.001) in the low dose. In the duodenum, gluten levels were reduced from 14.1 (8.3–124.7) in the placebo to 6.3 (3.5–19.8, p = 0.019) in the high dose and to 7.4 μg × min/ml in the low dose (3.8–12.0, p = 0.015). Thus even in a physiological meal setting, AN-PEP significantly degraded most gluten in the stomach before it entered the duodenum.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017
Keywords
Gluten
National Category
Nutrition and Dietetics
Research subject
Nutrition
Identifiers
urn:nbn:se:oru:diva-61493 (URN)10.1038/s41598-017-13587-7 (DOI)000412950900035 ()29026170 (PubMedID)2-s2.0-85031294461 (Scopus ID)
Note

Funding Agency:

DSM

Available from: 2017-10-12 Created: 2017-10-12 Last updated: 2017-11-10Bibliographically approved
Marques, T. M., Holster, S., Wall, R., König, J. & Brummer, R. J. (2016). Correlating the gut microbiome to health and disease. In: Niall Hyland, Catherine Stanton (Ed.), The Gut-Brain Axis: Dietary, Probiotic, and Prebiotic Interventions on the Microbiota (pp. 261-291). Elsevier
Open this publication in new window or tab >>Correlating the gut microbiome to health and disease
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2016 (English)In: The Gut-Brain Axis: Dietary, Probiotic, and Prebiotic Interventions on the Microbiota / [ed] Niall Hyland, Catherine Stanton, Elsevier, 2016, p. 261-291Chapter in book (Refereed)
Abstract [en]

The gut microbiota is a complex ecosystem consisting of a diverse population of prokaryotes that has a symbiotic relationship with its host; thus it plays a vital role for the host’s health. Our understanding of the effect of the gut microbiome in health and disease has grown substantially over the past 2 decades, mostly because of recent advances in sequencing and other high-throughput technologies. Given its high metabolic potential, close proximity to the intestinal mucosa, and interaction with the immune system, it is not surprising that the gut microbiome is an important partaker in human health. Evidence to the importance of the gut microbiome in human health and disease is the growing number of conditions now linked to changes in the resident gut microbiota, including recurrent Clostridium difficile infections, inflammatory bowel disease, irritable bowel syndrome, colorectal cancer, allergies, neurological diseases, and metabolic diseases. Research into this field of the association of the gut microbiome with health and disease continues to expand at a rapid pace as we come to accept the gut microbiome as our “second genome.” Targeting the gut microbiome to restore/modulate its composition with the use of antibiotics, probiotics, prebiotics, and even fecal microbiota transplantation is considered a promising future strategy for the development of new solutions in the treatment of various diseases associated with an imbalance in microbiota composition and functioning.

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
Gut microbiota, Immune system-related diseases, Intestinal diseases, Metabolic diseases, Nervous system-related diseases, Therapies for gut microbiota modulation
National Category
Medical and Health Sciences Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-65939 (URN)10.1016/B978-0-12-802304-4.00012-8 (DOI)2-s2.0-85011779736 (Scopus ID)978-0-12-802304-4 (ISBN)
Available from: 2018-03-21 Created: 2018-03-21 Last updated: 2019-04-24Bibliographically approved
Holster, S., Repsilber, D., Geng, D., Hyötyläinen, T., Lindqvist, C. M., de Vos, W., . . . König, J.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
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(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
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-4204-6811

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