Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial

Fecal Microbiota Transplantation for Ulcerative Colitis: Not Just Yet

Results of the First Pilot Randomized Controlled Trial of Fecal Microbiota Transplant In Pediatric Ulcerative Colitis: Lessons, Limitations, and Future Prospects

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

FMT may increase the proportion of people with active UC who achieve clinical and endoscopic remission. The evidence was very uncertain about whether use of FMT in people with active UC impacted the risk of serious adverse events or improvement in quality of life. The evidence was also very uncertain about the use of FMT for maintenance of remission in people with UC, as well as induction and maintenance of remission in people with CD, and no conclusive statements could be made in this regard. Further studies are needed to address the beneficial effects and safety profile of FMT in adults and children with active UC and CD, as well as its potential to promote longer-term maintenance of remission in UC and CD.

Background Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis(UC). We aim to establish the efficacy of multidonor, easy way FMT by capsules in active UC, and identify the factors associated with response to therapy. Methods We conducted a prospective trial in Zhongshan Hospital Affiliated to Xiamen University, Xiamen, China. A total of 28 adults with active UC (Mayo score 4–11) were enrolled in this trial, followed by capsules 3 days one week. One donor’s fecal microbiota was made into one capsule, and fecal microbiota transplantation was each derived from two or three unrelated donors. The primary outcome was steroid-free clinical remission with endoscopic remission or response. We performed 16S rDNA stool analysis to access associated microbial changes. Based on LC-MS/MS technology metabonomic researches were carried out to study metablome of the serum. Results The primary outcome with clinical remission was achieved in 16 out of 28 patients (57.14%), and 11 out of 22 patients(50%) had the musical healing. No adverse events were identified in these patients. The effects have no significant relationship with the age, gender, severity and extent of disease.FMT increased microbial diversity and altered composition. After FMT, unlike non-responders, the intestinal flora structure of responders was close to the donor, and the significant change began 1 week after transplantation. After FMT, responders had enrichment of Alloprevotella compared with non-responders and had increased levels of taurochenodeoxycholate and taurocholate. Escherichia-Shigella were decreased after FMT in responders, but no change in non-responders. The correlation analysis between the differential metabolites and the differential flora showed that the bile acid-related metabolites were positively correlated with the abundance of Alloprevotella and Prevotella_9. Conclusions Intensive-dosing, multidonor, FMT by capsules induces clinical remission in active ulcerative colitis and is associated with the changes of intestinal flora. Alloprecotella and bile acid-related metabolites were related to curative effect. The enrichment of Alloprevotella after FMT may be able to treat ulcerative colitis by regulating bile acid metabolism, improving mucosal permeability and regulating immunity. Future work should focus on the multi center verification and the relationship of immunity and gut microbiome.

Background Faecal microbiota transplantation (FMT) has been shown to be effective in active ulcerative colitis (UC) by targeting gut dysbiosis. We assessed the role of FMT in steroid-dependent UC patients. Methods In this trial, patients with steroid-dependent active UC were treated with FMT using random unrelated donors, by the colonoscopic approach, at weeks 0, 2, 6, 10, 14, 18 and 22. Patients with steroid-dependent UC treated who were treated without FMT in past, with azathioprine as a steroid-sparing agent were taken as historical controls. The primary outcome was the achievement of steroid-free clinical remission (Mayo score=30% and ≥3 points compared to baseline) and endoscopic remission (Mayo score 0 or 1). 16 s rRNA gene sequencing was done for analysing changes in microbial composition after FMT. Results Between September 2015 – September 2017, 41 patients with steroid-dependent UC underwent FMT, 33 completed seven sessions over 22 weeks while 8 discontinued treatment (non-response: 5, lost to follow up: 2, fear of side effects: 1) (figure 1). At week 22, the primary endpoint (steroid-free clinical remission) was achieved in 46.3% (19/41) patients treated with FMT compared to 26.3% (10/38) in historical controls treated with azathioprine (p=0.065). Clinical response (31/41, 75.6%) and endoscopic remission (26/41, 63.4%) with FMT were significantly higher than controls (55.3% and 39.5% respectively, p=0.005) (IDDF2018-ABS-0218 Figure 2). Adverse events necessitating discontinuation were noted in 3/38 (7.89%) controls treated with azathioprine, but not with FMT. Conclusions A multi-session FMT by a colonoscopic route is a promising therapeutic option for steroid-dependent UC patients, as it induces clinical remission and withdrawal of steroids in 46.3% and 75.6% patients respectively.

Nutritional and Botanical Approaches for Inflammatory Bowel Disease

<h3>Background</h3> Fecal microbiota transplantation (FMT) targeting gut microbiome dysbiosis is an emerging therapy for ulcerative colitis (UC) and has been found to be efficacious in multiple randomized trials. However, there is no uniformity in protocols with respect to the route of administration, the frequency of intervention and amount of fecal slurry delivered. We intend to study the pattern of response to serial fecal microbiota transplantation via the colonoscopic route in patients with ulcerative colitis. <h3>Methods</h3> A retrospective analysis of patients with active UC (Mayo clinic score ≥4), who received multi-session FMT (at weeks 0, 2, 6, 10, 14, 18 and 22) via a colonoscopic route, in addition to standard of care, between June 2015 and December 2018 was done. The proportion of patients maintaining steroid-free clinical remission (Mayo score ≤2, all sub scores ≤ 1) and achieving endoscopic remission (endoscopic Mayo score 0) were calculated for each FMT session. <h3>Results</h3> One hundred twenty-four patients [mean age 34.84 ±11.91 years, 66.93% males (n=83), mean mayo clinic score 8.13 ± 2.65] who consented for FMT were analysed retrospectively. Proportion of patients maintaining steroid-free clinical remission (Mayo score ≤2, all sub scores ≤ 1)as well as achieving endoscopic remission (endoscopic Mayo score 0)increased with serial sessions of FMT (16.6% after 1^st session vs 65.55% after 7^th session for clinical remission and 3.62% after 1^st session vs 37.93% after 7^th session for endoscopic remission). (figure 1) <h3>Conclusions</h3> With serial colonoscopic FMTs for active ulcerative colitis, the response rates, determined by the maintenance of steroid-free clinical remission and endoscopic remission, gradually increase. Repeated interventions over longer periods may result in a persistent change in gut microbiota composition that is otherwise inherently resilient, resulting in improvement in disease activity indices.

Background Faecal microbiota transplant (FMT) is an effective treatment strategy for recurrent Clostridioides difficile infection (rCDI)1, but its role in ulcerative colitis (UC), another disease involving gut dysbiosis, is less certain2. Methods Patients with active UC at St Thomas’ hospital, London were given FMT according to patient preference and MDT decision. Local approval was granted for the new procedure process in May 2018. 200ml FMT (80g stool in 0.9% saline with 12.5% glycerol) was deposited in the terminal ileum or caecum at colonoscopy, with loperamide and an anal plug to aid retention. 60-90ml FMT was given via enema on days 2, 4 and 28. Demographics (table 1), Simple Clinical Colitis Activity Index (SCCAI), Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and faecal calprotectin were collected at baseline and over a 12-week follow-up (FU) period. Adverse events, hospital admissions, medication changes and colectomy incidence were recorded. Results 10 FMT administrations across 9 patients between 2018 and 2024 were analysed retrospectively. All patients had improvement in at least one measurable index (SCCAI, UCEIS or calprotectin, mean FU 6 weeks for each parameter). In all measured cases SCCAI either improved (5/6; 83%) or remained static in steroid free clinical remission (1/6, 17%), mean improvement = 2.83. 2/6 (33%) were in steroid free clinical remission after FMT. UCEIS improved in 3/5 (60%) and remained static in 2/5 (40%), mean improvement = 1. Endoscopic response (improvement ≥2) occurred in 1/5 (20%). None achieved endoscopic remission during 12-week FU. Faecal calprotectin improved in all measured cases (n=4) and by ≥50% in 2/4 (50%), but all were receiving steroids either at the time of FMT or during FU. Steroids were started in 1/9 (11%) and biologic switched in 4/9 (44%) &amp;lt;12 weeks after FMT. 2/9 (22%) had a biologic switch or dose escalation beyond 12 weeks. 2/9 (22%) required no change in treatment (figure 1). There were no adverse events, hospitalisations or colectomy during 12-week FU period. 2/9 patients went on to have colectomy, both &amp;gt;2 years post FMT. Conclusion There was clinical response or maintenance of clinical remission after FMT in all patients. This was discordant with a relatively modest endoscopic improvement, suggesting a potential placebo effect. Most patients required a change of treatment either during the 12-week FU or shortly after. Analysis was limited by other concurrent medication changes and incomplete data. Extension of FMT administration may have captured further response but this would need further evaluation. FMT was safe to deliver with no adverse events documented, no hospitalisations and no colectomy during 12-week FU.

Aim Increasing evidence supports the role of the gut microbiota in the etiology of ulcerative colitis (UC). Fecal microbiota transplantation (FMT) is a highly effective treatment against recurrent Clostridium difficile infection; however, its efficacy in UC is still controversial. A systematic review and meta-analysis was conducted to evaluate the efficacy and safety of FMT for treatment of active UC. Methods We searched Cochrane, Medline, Web of Science, and Embase from inception to February 2020. Randomized controlled trials (RCTs) recruiting adults with active UC, which compared FMT with controls, were eligible. The primary outcome was combined clinical remission with endoscopic remission/response. Secondary outcomes included clinical remission, endoscopic remission, and serious adverse events. Relative risk (RR) with 95% confidence interval (CI) is reported. Results Five RCTs with 292 participants were eligible for inclusion. When data were pooled for all patients, FMT was associated with a higher combined clinical remission with endoscopic remission/response; the RR of combined outcome not achieving after FMT vs. control was 0.79 (95% CI 0.70-0.88). FMT delivered via lower gastrointestinal route was superior to upper gastrointestinal route with regard to combined clinical remission with endoscopic remission/response (RR = 0.79, 95% CI 0.70-0.89). FMT with pooled donor stool (RR = 0.69, 95% CI 0.56-0.85) and higher frequency of administration (RR = 0.76, 95% CI 0.62-0.93) may be more effective with regard to clinical remission. There was no statistically significant difference in serious adverse events with FMT compared with controls (RR = 0.98, 95% CI 0.93-1.03). Conclusion FMT shows a promising perspective with comparable safety and favorable clinical efficacy for the treatment of active UC in the short term. However, further larger, more rigorously conducted RCTs of FMT in UC are still needed in order to resolve the controversial questions.

<h3>Background</h3> Though faecal microbiota transplantation (FMT) has been shown to be efficacious for induction of remission in patients with active UC, the long-term clinical outcomes after initial response have not been assessed. <h3>Methods</h3> This single-blind, randomised, placebo-controlled trial was conducted at Dayanand Medical College and Hospital, India. Patients with active UC (Mayo score 4–10) who achieved clinical remission with multi-session FMT (0, 2, 6, 10, 14, 18 and 22 weeks) were randomly allocated in a 1:1 ratio to either maintenance FMT or placebo colonoscopic infusion every 8 weeks till 48 weeks. The primary endpoint was the maintenance of steroid-free clinical remission (Mayo score ≤2), and secondary endpoints were the achievement of deep remission (clinical and endoscopic remission, i.e. endoscopic Mayo score 0) and histological remission (Nancy grade 0, 1) at the end of 48 weeks. Clinical disease activity and adverse events were assessed at each visit or earlier in case of worsening of symptoms. The analysis was done by intention-to-treat and included all patients who underwent one session of FMT after initial clinical remission at week 22. <h3>Results</h3> Forty-three of 78 patients treated with multi-session FMT achieved clinical remission, 22 of these were randomly assigned to receive FMT and 21 received placebo, colonoscopically every 8 weeks. The primary outcome was achieved in 19/22 (86.4%) patients allocated FMT versus 14/21 (66.7%) patients assigned placebo (p=0.126). Secondary endpoints of deep remission [18/22 (81.8%) with FMT versus 8/21 (38.1%) with placebo p=0.003] and histological remission [12/22 (54.5%) with FMT versus 3/21 (14.3%) with placebo p=0.006] were achieved in a significantly higher number of patients with FMT. Two patients receiving FMT and 5 patients on placebo relapsed. All relapses were treated with steroids. There were no serious adverse events necessitating discontinuation in patients on FMT, 1 patient who relapsed on placebo required colectomy. <h3>Conclusions</h3> Maintenance therapy with FMT is required in patients who had earlier been treated with FMT for induction of remission. Moreover, FMT also enhances achievement of deep and histological remission.

BackgroundPredictive markers for the outcomes of fecal microbiota transplantation (FMT) in ulcerative colitis (UC) are poorly defined. Existing microbial analyses of FMT efficacy are based on time-consuming and costly sequencing...

Refractory ulcerative colitis (UC), characterized by persistent disease activity despite optimized medical therapy, poses a significant therapeutic challenge. Fecal microbiota transplantation (FMT) has shown promise in inducing remission in active ulcerative colitis (UC) by restoring gut microbial balance; however, its efficacy in refractory cases remains unclear. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of FMT in achieving clinical and endoscopic remission in patients with refractory UC, based on evidence from randomized controlled trials (RCTs). We searched PubMed, Scopus, Google Scholar Cochrane CENTRAL, and Web of Science up to February 2025 for RCTs comparing FMT to placebo or standard care in adults with refractory UC (Mayo Score ≥ 3 despite treatment). Primary outcomes were clinical remission (Mayo Score ≤ 2, no subscore > 1) and endoscopic remission (Mayo endoscopic subscore ≤ 1). Data were pooled using a random-effects model, with heterogeneity assessed via I² and Q-tests. Subgroup analyses explored age at diagnosis and disease duration as moderators. The review followed PRISMA guidelines and was registered with PROSPERO (CRD420250651790). Six RCTs were included. FMT showed no significant effect on clinical remission (pooled estimate - 0.2584; 95% CI - 0.9031 to 0.3863; p = 0.4321) or endoscopic remission (pooled estimate - 0.2229; 95% CI - 0.8811 to 0.4353; p = 0.5069), with no heterogeneity (I² = 0.00%). Subgroup analyses revealed no moderation by age or disease duration (p > 0.27). Adverse events were mild and transient. FMT does not significantly improve clinical or endoscopic remission in refractory UC, suggesting limited efficacy in this population despite a favorable safety profile. Larger, standardized trials are warranted.

Background Emerging evidence suggests that faecal microbiota transplantation (FMT) can induce remission in patients with refractory to standard treatment ulcerative colitis (UC). Methods We performed a systematic review and network meta-analysis to assess the comparative efficacy and safety of FMT and current therapies as induction treatments in UC. We searched Medline, Embase, CENTRAL and grey literature sources up to October 2019. We included randomised controlled trials of patients with active UC that compared FMT, infliximab, adalimumab, golimumab, vedolizumab and tofacitinib to each other or placebo. Efficacy outcomes were clinical remission and response. Safety outcomes were incidence of any adverse event (AE), serious AEs and infections. We conducted random-effects network meta-analysis and ranked treatments based on the surface under the cumulative ranking (SUCRA) probabilities. Results Twenty trials (5177 patients) were included in the analysis. There was only one head to head RCT (vedolizumab vs. adalimumab). FMT was superior to placebo for induction of clinical remission (OR 2.80; 95% CI 1.50–5.23) and response (OR 2.53; 95% CI 1.53–4.20). No indirect comparisons between FMT and licensed treatments reached statistical significance for efficacy outcomes. On SUCRA analysis, FMT (SUCRA 0.57, 0.58) had comparable SUCRA values with golimumab (SUCRA 0.53, 0.39) and vedolizumab (SUCRA 0.58, 0.61) in terms of clinical remission and response respectively. Infliximab (SUCRA 0.71, 0.93) and tofacitinib (SUCRA 0.85, 0.75) were ranked highest while adalimumab (SUCRA 0.23, 0.21) was ranked lowest. There was no increase in the rates of any AEs for FMT and licensed therapies and no differences in indirect comparisons. Vedolizumab (SUCRA 0.81) was the safest option, followed by tofacitinib (SUCRA 0.55). FMT (SUCRA 0.38) had comparable SUCRA values with adalimumab (SUCRA 0.37) and golimumab (SUCRA 0.47). Only tofacitinib increased the incidence of infections compared with placebo (OR 1.51; 95%CI 1.05–2.19). Based on SUCRAs, FMT (SUCRA 0.83) was the safest in terms of infections. Vedolizumab had lower incidence of serious AEs compared with FMT and placebo, while FMT was ranked as the least safe treatment. In subgroup analysis, FMT through the lower gastrointestinal (GI) tract was superior to placebo (OR 3.92; 95%CI 1.94–7.92) and performed numerically better than FMT through the upper GI tract (OR 0.29; 95%CI 0.08–1.13). Conclusion Evidence suggests that FMT could be an efficacious and safe alternative induction therapy for refractory UC. Lower GI delivery of FMT might be more effective. Due to the absence of head-to-head trials and the limited size of FMT trials, conclusions must be interpreted with caution.

BackgroundFecal microbiota transplantation is an effective treatment for many gastrointestinal diseases, such as Clostridium difficile infection and inflammatory bowel disease, especially ulcerative colitis. Changes in colonic microflora may play an important role in the pathogenesis of ulcerative colitis, and improvements in the intestinal microflora may relieve the disease. Fecal bacterial transplants and oral probiotics are becoming important ways to relieve active ulcerative colitis.PurposeThis systematic review with meta-analysis compared the efficacy and safety of basic treatment combined with fecal microbiota transplantation or mixed probiotics therapy in relieving mild to moderate ulcerative colitis.MethodsThe PubMed, Embase, and Cochrane libraries (updated September 2019) were searched to identify randomized, placebo-controlled, or head-to-head trials assessing fecal microbiota transplantation or probiotic VSL#3 as induction therapy in active ulcerative colitis. We analyze data using the R program to obtain evidence of direct comparison and to generate intermediate variables for indirect treatment comparisons.ResultsSeven randomized, double-blind, placebo-controlled trials were used as the sources of the induction data. All treatments were superior to placebo. In terms of clinical remission and clinical response to active ulcerative colitis, direct comparisons showed fecal microbiota transplantation (OR = 3.47, 95% CI = 1.93–6.25) (OR = 2.48, 95% CI = 1.18–5.21) and mixed probiotics VSL#3 (OR = 2.40, 95% CI = 1.49–3.88) (OR = 3.09, 95% CI = 1.53–6.25) to have better effects than the placebo. Indirect comparison showed fecal microbiota transplantation and probiotic VSL#3 did not reach statistical significance either in clinical remission (RR = 1.20, 95% CI = 0.70–2.06) or clinical response (RR = 0.95, 95% CI = 0.62–1.45). In terms of safety, fecal microbiota transplantation (OR = 1.15, 95% CI = 0.51–2.61) and VSL #3 (OR = 0.90, 95% CI = 0.33–2.49) showed no statistically significant increase in adverse events compared with the control group. In terms of serious adverse events, there was no statistical difference between the fecal microbiota transplantation group and the control group (OR = 1.29, 95% CI = 0.46–3.57). The probiotics VSL#3 seems more safer than fecal microbiota transplantation, because serious adverse events were not reported in the VSL#3 articles.ConclusionsFecal microbiota transplantation or mixed probiotics VSL#3 achieved good results in clinical remission and clinical response in active ulcerative colitis, and there was no increased risk of adverse reactions. There was no statistical difference between the therapeutic effect of fecal microbiota transplantation and that of mixed probiotics VSL#3. However, the use of fecal microbiota transplantation and probiotics still has many unresolved problems in clinical applications, and more randomized controlled trials are required to confirm its efficacy.