Lyophilised oral faecal microbiota transplantation for ulcerative colitis (LOTUS): a randomised, double-blind, placebo-controlled trial

ObjectiveIBS is associated with an intestinal dysbiosis and faecal microbiota transplantation (FMT) has been hypothesised to have a positive effect in patients with IBS. We performed a randomised, double-blind placebo-controlled trial to investigate if FMT resulted in an altered gut microbiota and improvement in clinical outcome in patients with IBS.DesignWe performed this study in 52 adult patients with moderate-to-severe IBS. At the screening visit, clinical history and symptoms were assessed and faecal samples were collected. Patients were randomised to FMT or placebo capsules for 12 days and followed for 6 months. Study visits were performed at baseline, 1, 3 and 6 months, where patients were asked to register their symptoms using the IBS-severity scoring system (IBS-SSS) and IBS-specific quality of life (IBS-QoL). Prior to each visit, faecal samples were collected.ResultsA significant difference in improvement in IBS-SSS score was observed 3 months after treatment (p=0.012) favouring placebo. This was similar for IBS-QoL data after 3 months (p=0.003) favouring placebo. Patients receiving FMT capsules had an increase in faecal microbial biodiversity while placebos did not.ConclusionIn this randomised double-blinded placebo-controlled study, we found that FMT changed gut microbiota in patients with IBS. But patients in the placebo group experienced greater symptom relief compared with the FMT group after 3 months. Altering the gut microbiota is not enough to obtain clinical improvement in IBS. However, different study designs and larger studies are required to examine the role of FMT in IBS.Trial registration numberNCT02788071.

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OP30 Lyophilised orally administered faecal microbiota transplantation for Active Ulcerative Colitis (LOTUS study)

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab075.029 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S029-S029

Author(s):

C Haifer ◽

A Saikal ◽

S Paramsothy ◽

T J Borody ◽

S Ghaly ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Remission ◽

Controlled Trial ◽

Active Ulcerative Colitis ◽

Faecal Microbiota ◽

Double Blind ◽

Faecal Microbiota Transplantation ◽

Endoscopic Remission ◽

Remission Rates ◽

Pre Treatment

Abstract Background Faecal microbiota transplantation (FMT) administered via the lower GI tract effectively induces remission in ulcerative colitis (UC). Orally administered FMT capsules may improve patient tolerability and facilitate maintenance therapy while it is unclear if pre-FMT antibiotics enhance therapeutic efficacy. Methods We performed a dual-centre randomised, double blind, placebo-controlled trial of oral lyophilised FMT in adults with mild-moderately active UC (total Mayo 4–10). All subjects received 2-weeks of pre-FMT antibiotics (amoxycillin, metronidazole and doxycycline) before 1:1 randomisation to either oral FMT (0.35g stool content per capsule from 1 of 2 healthy donors) or identical placebo for 8 weeks. Enforced tapering and cessation of corticosteroids was mandated. The primary endpoint was week 8 steroid-free clinical remission with endoscopic remission or response (total Mayo score ≤2 with subscores ≤ 1 for rectal bleeding, stool frequency and endoscopic appearance, and ≥1-point reduction from baseline in endoscopy subscore). Responders to FMT induction were re-randomised to either continue maintenance FMT or withdrawal of FMT with final outcomes assessed at week 56. Results Recruitment was paused due to the COVID-19 pandemic. 37 patients were randomised. Baseline patient and disease characteristics were balanced between the randomised groups. The primary outcome was achieved in 8/16 (50%) receiving FMT versus 3/19 (16%) receiving placebo (OR: 4.63; 95%CI: 1.74–12.30; P=0.002). Steroid-free clinical remission rates and endoscopic remission rates were 69% vs 26% (P=0.012) and 44% vs 16% (P=0.074) in the FMT and placebo arms, respectively. Reported SAE were worsening colitis (2 FMT, 1 placebo) and PR bleeding relating to previous anal surgery (placebo). Ten patients entered the maintenance withdrawal study. Steroid-free clinical, endoscopic and histologic remission was achieved in 4/4 patients who continued daily oral FMT, with all 6 patients randomised to FMT withdrawal having a flare of disease with a median time to relapse of 6 months. Conclusion Oral lyophilised FMT following antibiotic pre-treatment for mild-moderately active ulcerative colitis was associated with a significant increased rate of clinical remission with endoscopic remission or response versus antibiotic treatment alone at week 8. Pre-treatment antibiotics had an additive impact upon treatment efficacy compared with previous studies utilising FMT. Maintenance FMT therapy was associated with sustained clinical, endoscopic and histologic remission at week 56. Treatment was well tolerated and there were no new safety signals related to FMT therapy.

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Faculty Opinions recommendation of Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.737113055.793574215 ◽

2020 ◽

Author(s):

Ian Beales

Keyword(s):

Irritable Bowel Syndrome ◽

Controlled Study ◽

Faecal Microbiota ◽

Double Blind ◽

Double Blind Placebo ◽

Faecal Microbiota Transplantation ◽

Irritable Bowel

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Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study

Gut ◽

10.1136/gutjnl-2019-319630 ◽

2019 ◽

Vol 69 (5) ◽

pp. 859-867 ◽

Cited By ~ 36

Author(s):

Magdy El-Salhy ◽

Jan Gunnar Hatlebakk ◽

Odd Helge Gilja ◽

Anja Bråthen Kristoffersen ◽

Trygve Hausken

Keyword(s):

Irritable Bowel Syndrome ◽

Secondary Outcome ◽

Controlled Study ◽

Rrna Gene ◽

Faecal Microbiota ◽

Double Blind ◽

Double Blind Placebo ◽

Faecal Microbiota Transplantation ◽

Link Type ◽

Irritable Bowel

ObjectiveFaecal microbiota transplantation (FMT) from healthy donors to patients with irritable bowel syndrome (IBS) has been attempted in two previous double-blind, placebo-controlled studies. While one of those studies found improvement of the IBS symptoms, the other found no effect. The present study was conducted to clarify these contradictory findings.DesignThis randomised, double-blind, placebo-controlled study randomised 165 patients with IBS to placebo (own faeces), 30 g FMT or 60 g FMT at a ratio of 1:1:1. The material for FMT was obtained from one healthy, well-characterised donor, frozen and administered via gastroscope. The primary outcome was a reduction in the IBS symptoms at 3 months after FMT (response). A response was defined as a decrease of 50 or more points in the total IBS symptom score. The secondary outcome was a reduction in the dysbiosis index (DI) and a change in the intestinal bacterial profile, analysed by 16S rRNA gene sequencing, at 1 month following FMT.ResultsResponses occurred in 23.6%, 76.9% (p<0.0001) and 89.1% (p<00.0001) of the patients who received placebo, 30 g FMT and 60 g FMT, respectively. These were accompanied by significant improvements in fatigue and the quality of life in patients who received FMT. The intestinal bacterial profiles changed also significantly in the groups received FMT. The FMT adverse events were mild self-limiting gastrointestinal symptoms.ConclusionsFMT is an effective treatment for patients with IBS. Utilising a well-defined donor with a normal DI and favourable specific microbial signature is essential for successful FMT. The response to FMT increases with the dose.Trial registrationwww.clinicaltrials.gov (NCT03822299) and www.cristin.no (ID657402).

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600 Multi Donor Intense Faecal Microbiota Transplantation is an Effective Treatment for Resistant Ulcerative Colitis: A Randomised Placebo-Controlled Trial

Gastroenterology ◽

10.1016/s0016-5085(16)30517-0 ◽

2016 ◽

Vol 150 (4) ◽

pp. S122-S123 ◽

Cited By ~ 17

Author(s):

Sudarshan Paramsothy ◽

Michael A. Kamm ◽

Alissa Walsh ◽

Johan van den Bogaerde ◽

Douglas Samuel ◽

...

Keyword(s):

Ulcerative Colitis ◽

Effective Treatment ◽

Controlled Trial ◽

Faecal Microbiota ◽

Faecal Microbiota Transplantation

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OP036 Short duration, low intensity pooled faecal microbiota transplantation induces remission in patients with mild-moderately active ulcerative colitis: a randomised controlled trial

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjx002.035 ◽

2017 ◽

Vol 11 (suppl_1) ◽

pp. S23-S23 ◽

Cited By ~ 21

Author(s):

S. Costello ◽

O. Waters ◽

R. Bryant ◽

R. Katsikeros ◽

J. Makanyanga ◽

...

Keyword(s):

Ulcerative Colitis ◽

Randomised Controlled Trial ◽

Short Duration ◽

Controlled Trial ◽

Active Ulcerative Colitis ◽

Faecal Microbiota ◽

Faecal Microbiota Transplantation ◽

Low Intensity ◽

Randomised Controlled

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No benefit of faecal microbiota transplantation for IBS-D

Drug and Therapeutics Bulletin ◽

10.1136/dtb.2020.000013 ◽

2020 ◽

Vol 58 (6) ◽

pp. 87-87

Keyword(s):

Irritable Bowel Syndrome ◽

Controlled Trial ◽

Faecal Microbiota ◽

Double Blind ◽

Faecal Microbiota Transplantation ◽

Irritable Bowel

AbstractReview of: Aroniadis OC, Brandt LJ, Oneto C, et al. Faecal microbiota transplantation for diarrhoea-predominant irritable bowel syndrome: a double-blind, randomised, placebo-controlled trial. Lancet Gastroenterol Hepatol 2019;4:675–85.

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