Microbiota Transplantation For Ulcerative Colitis Research Articles

Dynamics of Gut Microbiota after Fecal Microbiota Transplantation in Ulcerative Colitis: Success Linked to Control of Prevotellaceae.

Fecal microbiota transplantation (FMT) is an experimental treatment for ulcerative colitis (UC). We aimed to study microbial families associated with FMT treatment success. We analyzed stools from 24 UC patients treated with four FMTs weekly after randomization for pretreatment during three weeks with budesonide (n = 12) or placebo (n = 12). Stool samples were collected nine times pre-, during, and post FMT. Clinical and endoscopic response was assessed 14 weeks after initiation of the study using the full Mayo score. Early withdrawal due to worsening of UC symptoms was classified as non-response. Nine patients (38%) reached remission at week 14, and 15 patients had a partial response or non-response at or before week 14. With a Dirichlet Multinomial Mixture model we identified five distinct clusters based on the microbiota composition of 180 longitudinally collected patient samples and 27 donor samples. A Prevotellaceae-dominant cluster was associated with poor response to FMT treatment. Conversely, the families Ruminococcaceae and Lachnospiraceae were associated with a successful clinical response. These associations were already visible at the start of the treatment for a subgroup of patients and were retained in repeated measures analyses of family-specific abundance over time. Responders were also characterized by a significantly lower Simpson dominance compared to non-responders. The success of FMT treatment of UC patients appears to be associated with specific gut microbiota families, such as control of Prevotellaceae. Monitoring the dynamics of these microbial families could potentially be used to inform treatment success early during FMT.

Anti-inflammatory Effects of Bacteroidota Strains Derived From Outstanding Donors of Fecal Microbiota Transplantation for the Treatment of Ulcerative Colitis.

The proportion of certain Bacteroidota species decreased in patients with ulcerative colitis, and the recovery of Bacteroidota is associated with the efficacy of fecal microbiota transplantation therapy. We hypothesized that certain Bacteroidota may advance ulcerative colitis treatment. Accordingly, we aimed to evaluate the anti-inflammatory effects of Bacteroidota strains isolated from donors. Donors with proven efficacy of fecal microbiota transplantation for ulcerative colitis were selected, and Bacteroidota strains were isolated from their stools. The immune function of Bacteroidota isolates was evaluated through in vitro and in vivo studies. Twenty-four Bacteroidota strains were isolated and identified. Using an in vitro interleukin (IL)-10 induction assay, we identified 4 Bacteroidota strains with remarkable IL-10-induction activity. Of these, an Alistipes putredinis strain exhibited anti-inflammatory effects in a mouse model of colitis induced by sodium dextran sulfate and oxazolone. However, 16S rRNA gene-based sequencing analysis of A. putredinis cultures in the in vivo study revealed unexpected Veillonella strain contamination. A second in vitro study confirmed that the coculture exhibited an even more potent IL-10-inducing activity. Furthermore, the production of A. putredinis-induced IL-10 was likely mediated via toll-like receptor 2 signaling. This study demonstrated that A. putredinis, a representative Bacteroidota species, exhibits anti-inflammatory effects in vivo and in vitro; however, the effects of other Bacteroidota species remain unexplored. Our fecal microbiota transplantation-based reverse translation approach using promising bacterial species may represent a breakthrough in microbiome drug development for controlling dysbiosis during ulcerative colitis.

P1205 Features of the gut microbiota that associate with clinical outcomes of fecal microbiota transplantation in Ulcerative Colitis: a systematic review and meta-analysis

Abstract Background Evidence continues to accumulate highlighting the potential of fecal microbiota transplantation (FMT) to induce remission in patients with ulcerative colitis (UC). However, rational donor and recipient selection strategies and predictive biomarkers are needed to increase its efficacy. This systematic review provides a comprehensive evaluation of the current literature on microbial factors of FMT donors and UC recipients that relate to clinical outcomes. Methods The MEDLINE, Embase and Cochrane databases were systematically searched through April 2023 for relevant studies. The quality of studies and risk of bias was analyzed with Joanna Briggs tools and a compound critical appraisal-score. Additionally, species-level data from two randomized controlled trials (TURN and FOCUS) were re-analyzed from a compositional perspective. Results Out of 2983 citations identified, 47 met the inclusion criteria, of which 20 fulfilled quality appraisal. Higher clinical response rates were associated with higher bacterial alpha-diversity of stools of UC recipients at baseline and following FMT, and with higher FMT donor alpha-diversity. Engraftment of the donors’ microbiota was often reported but could not be clearly linked to clinical response, possibly because not every donor has an ideal microbiome. Taxa most frequently reported to be related to response included members of the Lachnospiraceae family (e.g., Eubacterium rectale, Blautia obeum) and Oscillospiraceae family (e.g., Faecalibacterium prausnitzii, Ruminococcus bromii) whereas members of the Proteobacteria and Fusobacteria phyla and Ruminococcus gnavus were reported to correlate to non-response. Low virome richness and low Caudovirales bacteriophages at baseline as well as a decrease of Candida levels following FMT, were associated with clinical response. Compositional analyses showed that a clinical response is associated with a shift away from a low diversity, Bacteroides2-enterotype-like composition towards one of high diversity either dominated by various butyrate producers, the Christensenellaceae-Methanobrevibacter trophic network or a high diversity composition with abundant but not excessive levels of Prevotella copri. Conclusion In this systematic review we found distinctive features of microbial profiles of both donors and UC recipients to relate to clinical response to FMT. The predictive value of microbial markers should be further explored in future clinical studies to move towards a personalized FMT approach and delineate ‘super-donor’ profiles.

What is the "optimal formula" for donor selection and feces processing for fecal microbiota transplantation in ulcerative colitis?

What is the "optimal formula" for donor selection and feces processing for fecal microbiota transplantation in ulcerative colitis?

S112 Optimal Timing and Donor-Patient Matching of Fecal Microbiota Transplantation for Ulcerative Colitis

Background: In recent years, rectifying imbalances of the gut microbiota with fecal microbiota transplantation (FMT) from healthy donors to patients suffering Ulcerative colitis (UC) have gained clinical interest. As several ongoing trials are exploring the possibility of using FMT to treat UC, discerning factors associated the long-term efficacy of FMT treatment becomes important. Our present study explored the factors related to the efficacy of FMT combined with triple-antibiotic therapy [amoxicillin, fosfomycin, and metronidazole (AFM); (A-FMT)] in patients with UC. Methods: Patients aged 16 years or older suffering from active UC with a Lichtiger’s clinical activity index (CAI) score ≥4 or Mayo endoscopic score (MES) ≥1 participated in the clinical study between March 2014 and October 2019. After rigorous screening, we selected relatives aged 20 years or older, or other volunteer donors. After 2 weeks of oral administration of 3 antibacterial agents, about 200ml of fresh or frozen stool solution of donor stool dissolved in saline solution was obtained by colonoscopy. CAI score at 4 weeks after treatment was defined as "response" if the CAI was ≤9 points and improved by ≥3 points, "remission" if the CAI further improved to ≤3 points, and "relapse" if the CAI increased or treatment was intensified at 48 weeks after treatment in the effective group. Results: Ninety-seven patients (68 males, 29 females, age 39.2 ± 12.9 years, disease duration 8.5 ± 8.0 years, CAI 10.7 ± 3.0, Mayo endoscopic subscore (MES) 1.8 ± 0.7) and 62 donors were included. 93 patients completed A-FMT, with an efficacy rate of 63.9% (ITT) at 4 weeks of treatment and a remission induction rate of 36.1%. The short-term efficacy was associated with pre-treatment Mayo endoscopic score (response P = 0.001, remission P < 0.001), history of corticosteroid treatment (response P = 0.04, remission P = 0.01), and history of tacrolimus treatment (response P = 0.04, remission P = 0.14). The cumulative non-relapse rate was significantly higher in the sibling donor group than in the parent-child donor group (P = 0.001). The age difference between patients and donors also affected the cumulative non-relapse rate (P = 0.01). Conclusion: In our study, the optimal timing for patients to receive A-FMT is before corticosteroid and tacrolimus treatments, and early-stage patients receive fecal transplants from siblings with the best clinical outcomes. While the short-term efficacy of A-FMT was related to the patient's own characteristics, the long-term efficacy was related to patient-donor matching.

Exploration of Potential Gut Microbiota-Derived Biomarkers to Predict the Success of Fecal Microbiota Transplantation in Ulcerative Colitis: A Prospective Cohort in Korea.

Background/AimsAlthough fecal microbiota transplantation (FMT) has been proven as one of the promising treatments for patients with ulcerative colitis (UC), potential prognostic markers regarding the clinical outcomes of FMT remain elusive.MethodsWe collected fecal samples of 10 participants undergoing FMT to treat UC and those from the corresponding donors. We categorized them into two groups responders and nonresponders. Sequencing of the bacterial 16S rRNA gene was conducted on the samples to explore bacterial composition.ResultsAnalyzing the gut microbiota of patients who showed different outcomes in FMT presented a distinct microbial niche. Source tracking analysis showed the nonresponder group had a higher rate of preservation of donor microbiota, underscoring that engraftment degrees are not one of the major drivers for the success of FMT. At the phylum level, Bacteroidetes bacteria were significantly depleted (p<0.003), and three genera, including Enterococcus, Rothia, and Pediococcus, were enriched in the responder group before FMT (p=0.003, p=0.025, and p=0.048, respectively). Furthermore, we applied a machine learning algorithm to build a prediction model that might allow the prediction of FMT outcomes, which yielded an area under the receiver operating characteristic (ROC) curve of 0.844. Notably, the microbiota-based model was much better at predicting outcomes than the clinical features model (area under the ROC curve=0.531).ConclusionsThis study is the first to suggest the significance of indigenous microbiota of recipients as a critical factor. The result highlights that bacterial composition should be evaluated before FMT to select suitable patients and achieve better efficiency.

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

Faecal microbiota transplantation (FMT) delivered via colonoscopic infusion or enemas have been shown to induce remission in a proportion of patients with active ulcerative colitis. Whether orally administered FMT is effective in ulcerative colitis is unknown. We aimed to assess the efficacy of oral lyophilised FMT for the treatment of active ulcerative colitis. A double-blind, randomised, placebo-controlled trial was conducted at two centres in Australia. Eligible patients were aged 18-75 years with active ulcerative colitis (defined as clinical and endoscopic active ulcerative colitis, with a total Mayo score of 4-10, and a Mayo endoscopic subscore ≥1). After 2 weeks of amoxicillin, metronidazole, and doxycycline, patients were randomly assigned in a 1:1 ratio to receive either oral lyophilised FMT or placebo capsules for 8 weeks, using a prespecified computer-generated randomisation list with a permuted block size of 8. The primary outcome was corticosteroid-free clinical remission with endoscopic remission or response (total Mayo score ≤2, all subscores ≤1, and ≥1 point reduction in endoscopic subscore) at week 8. At week 8, FMT responders were randomly assigned (in a 1:1 ratio, permuted block size of 8) to either continue or withdraw FMT for a further 48 weeks. Analyses were done by modified intention-to-treat, including all patients who received at least one study dose. This trial is registered with Australian New Zealand Trial Registry, number ACTRN 12619000611123; this is the final report of the trial. Between May 20, 2019, and March 24, 2020, 35 patients were randomly assigned: 15 to receive FMT and 20 to receive placebo. Recruitment was terminated early due to the COVID-19 pandemic. At week 8, eight (53%) of 15 patients in the FMT group were in corticosteroid-free clinical remission with endoscopic remission or response, as were three (15%) of 20 patients in the placebo group (difference 38·3%, 95% CI 8·6-68·0; p=0·027; odds ratio 5·0, 95% CI 1·8-14·1). Adverse events occurred in 10 (67%) patients in the FMT group and 17 (85%) of those in the placebo group during the 8-week induction period, and were generally mild and self-limiting gastrointestinal complaints. Serious adverse events included worsening ulcerative colitis (two in the FMT group, one in the placebo group) and per-rectal bleeding (one in the placebo group). Ten patients in the FMT group who achieved a clinical or endoscopic response entered the maintenance phase and were randomly assigned to continue open-label FMT (n=4) or withdraw therapy (n=6). All four (100%) patients who continued FMT were in clinical, endoscopic, and histologic remission at week 56 compared with none of the patients who had FMT withdrawn. Antibiotics followed by orally administered FMT was associated with the induction of remission in patients with active ulcerative colitis. Continuing FMT was well tolerated and appeared to demonstrate clinical, endoscopic, and histological efficacy. Oral FMT could be a promising and feasible treatment option for patients with ulcerative colitis. St Vincent's Clinic Foundation, Gastroenterological Society of Australia, Gutsy Group.

Long-Term Efficacy of Low-Intensity Single Donor Fecal Microbiota Transplantation in Ulcerative Colitis and Outcome-Specific Gut Bacteria.

Aims: To assess the long-term efficacy and safety of single-donor, low-intensity fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), and to identify the outcome-specific gut bacteria.Design: Thirty-one patients with active UC (Mayo scores ≥ 3) were recruited, and all received FMT twice, at the start of the study and 2∼3 months later, respectively, with a single donor and a long-term follow-up. The fecal microbiome profile was accessed via 16S rRNA sequencing before and after FMT.Results: After the first FMT, 22.58% (7/31) of patients achieved clinical remission and endoscopy remission, with the clinical response rate of 67.74% (21/31), which increased to 55% (11/20) and 80% (16/20), respectively, after the second FMT. No serious adverse events occurred in all patients. During 4 years of follow-up, the mean remission period of patients was 26.5 ± 19.98 m; the relapse rate in the 12 remission patients was 33.33% within 1 year, and 58.3% within 4 years. At baseline, UC patients showed an enrichment in some proinflammatory microorganisms compared to the donor, such as Bacteroides fragilis, Clostridium difficile, and Ruminococcus gnavus, and showed reduced amounts of short-chain fatty acid (SCFA) producing bacteria especially Faecalibacterium prausnitzii. FMT induced taxonomic compositional changes in the recipient gut microbiota, resulting in a donor-like state. Given this specific donor, UC recipients with different outcomes showed distinct gut microbial features before and after FMT. In prior to FMT, relapse was characterized by higher abundances of Bacteroides fragilis and Lachnospiraceae incertae sedis, together with lower abundances of Bacteroides massiliensis, Roseburia, and Ruminococcus; Prevotella copri was more abundant in the non-responders (NR); and the patients with sustained remission (SR) had a higher abundance of Bifidobacterium breve. After FMT, the NR patients had a lower level of Bifidobacterium compared to those with relapse (Rel) and SR, while a higher level of Bacteroides spp. was observed in the Rel group.Conclusion: Low-intensity single donor FMT could induce long remission in active UC. The gut microbiota composition in UC patients at baseline may be predictive of therapeutic response to FMT.

Transferable Immunoglobulin A–Coated Odoribacter splanchnicus in Responders to Fecal Microbiota Transplantation for Ulcerative Colitis Limits Colonic Inflammation

Fecal microbiota transplantation (FMT) is an emerging treatment modality for ulcerative colitis (UC). Several randomized controlled trials have shown efficacy for FMT in the treatment of UC, but a better understanding of the transferable microbiota and their immune impact is needed to develop more efficient microbiome-based therapies for UC. Metagenomic analysis and strain tracking was performed on 60 donor and recipient samples receiving FMT for active UC. Sorting and sequencing of immunoglobulin (Ig) A-coated microbiota (called IgA-seq) was used to define immune-reactive microbiota. Colonization of germ-free or genetically engineered mice with patient-derived strains was performed to determine the mechanism of microbial impact on intestinal immunity. Metagenomic analysis defined a core set of donor-derived transferable bacterial strains in UC subjects achieving clinical response, which predicted response in an independent trial of FMT for UC. IgA-seq of FMT recipient samples and gnotobiotic mice colonized with donor microbiota identified Odoribacter splanchnicus as a transferable strain shaping mucosal immunity, which correlated with clinical response and the induction of mucosal regulatory T cells. Colonization of mice with O splanchnicus led to an increase in Foxp3+/RORγt+ regulatory T cells, induction of interleukin (IL) 10, and production of short chain fatty acids, all of which were required for O splanchnicus to limit colitis in mouse models. This work provides the first evidence of transferable, donor-derived strains that correlate with clinical response to FMT in UC and reveals O splanchnicus as a key component promoting both metabolic and immune cell protection from colitis. These mechanistic features will helpenable strategies to enhance the efficacy ofmicrobial therapy for UC. Clinicaltrials.gov ID NCT02516384.

Fecal Microbiota Transplantation for Ulcerative Colitis: Dispelling the "Yuck Factor".

Fecal Microbiota Transplantation for Ulcerative Colitis: Dispelling the "Yuck Factor".

An Immunologic Compatibility Testing Was Not Useful for Donor Selection in Fecal Microbiota Transplantation for Ulcerative Colitis.

Fecal microbiota transplantation (FMT) is an effective procedure against Clostridioides difficile infection (CDI), with promising but still suboptimal performance in other diseases, such as ulcerative colitis (UC). The recipient’s mucosal immune response against the donor’s microbiota could be relevant factor in the effectiveness of FMT. Our aim was to design and validate an individualized immune-based test to optimize the fecal donor selection for FMT. First, we performed an in vitro validation of the test by co-culturing lymphocytes obtained from the small intestine mucosa of organ donor cadavers (n=7) and microbe-associated molecular patterns (MAMPs) obtained from the feces of 19 healthy donors. The inflammatory response was determined by interleukin supernatant quantification using the Cytometric Bead Array kit (B&D). We then conducted a clinical pilot study with 4 patients with UC using immunocompetent cells extracted from rectal biopsies and MAMPs from 3 donor candidates. We employed the test results to guide donor selection for FMT, which was performed by colonoscopy followed by 4 booster instillations by enema in the following month. The microbiome engraftment was assessed by 16S rDNA massive sequencing in feces, and the patients were clinically followed-up for 16 weeks. The results demonstrated that IL-6, IL-8, and IL-1ß were the most variable markers, although we observed a general tolerance to the microbial insults. Clinical and colonoscopy remission of the patients with UC was not achieved after 16 weeks, although FMT provoked enrichment of the Bacteroidota phylum and Prevotella genus, with a decrease in the Actinobacteriota phylum and Agathobacter genus. The most relevant result was the lack of Akkermansia engraftment in UC. In summary, the clinical success of FMT in patients with UC appears not to be influenced by donor selection based on the explored recipient’s local immunological response to FMT, suggesting that this approach would not be valid for FMT fecal donor optimization in such patients.

Recurrent Acute Pancreatitis following Colonoscopic Fecal Microbiota Transplantation for Ulcerative Colitis

AbstractA 37-year-old man with corticosteroid-dependent ulcerative pancolitis was taken up for colonoscopic fecal microbiota transplant (FMT). Preparation for colonoscopy was done with 118 g polyethylene glycol (PEG) in 2 L water ingested over 2 hours, followed by clear fluids. 200 g of screened donor stool, blended with water was instilled into terminal ileum; cecum; and ascending, transverse, and descending colon. Eighteen hours following ingestion of PEG and 2 hours following FMT, he complained of severe epigastric pain with radiation to back. Serum lipase was 6,756 U/L. He was managed with intravenous (IV) fluids and symptomatic treatment with discontinuation of corticosteroids and 6-MP. Ultrasound did not reveal gall bladder stones or sludge. There was no history of alcohol intake. Contrast-enhanced computed tomography scan at 48 hours showed bulky pancreas with peripancreatic stranding. He recovered over a week with normalization of lipase. Three weeks later he again reported severe epigastric pain 14 hours following ingestion of PEG, this time prior to colonoscopic FMT. Serum lipase was 1,140 U/L; the procedure was deferred and he recovered with symptomatic treatment over 3 days. Maintenance colonoscopic FMT was performed 4 times over the following 2 years with sodium phosphate preparation with no recurrence of pain. MRCP showed no evidence of chronic pancreatitis. He remains in clinical and endoscopic steroid-free, thiopurine-free remission. PEG is a rare cause of acute pancreatitis and merits consideration in appropriate clinical setting.

Lyophilised Oral Faecal Microbiota Transplantation in Ulcerative Colitis - a Randomised Placebo-Controlled Trial

Lyophilised Oral Faecal Microbiota Transplantation in Ulcerative Colitis - a Randomised Placebo-Controlled Trial

Fecal Microbiota Transplantation for Ulcerative Colitis: An Evolving Therapy.

Fecal microbiota transplantation (FMT) is currently an approved treatment for recurrent and refractory Clostridioides difficile infection. However, its use in ulcerative colitis is at an early stage and significant gaps remain in our understanding of the mechanisms and logistics of its practical application. This article aims to look into specific issues which remain unsettled for use of FMT in ulcerative colitis including donor and recipient selection, route of administration, and duration of therapy. We also discuss optimal ways to assess response to FMT and the current state of FMT regulations. In addition, we postulate the impact of diet on the microbiome profile of the donor and recipient. We also suggest a change in the nomenclature from FMT to fecal microbiome transfer. FMT is an evolving therapy. There are several considerations for its use in UC but its use and role should be directed by further clinical trials.

Fecal Microbiota Transplantation for Ulcerative Colitis: The Optimum Timing and Gut Microbiota as Predictors for Long-Term Clinical Outcomes.

INTRODUCTION:The previous researches aimed to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for ulcerative colitis (UC) in a short-term observation. The present study aimed to explore the optimum timing of FMT for maintaining the long-term clinical benefits and to target the gut microbiota that may help to predict the long-term success or failure of FMT in UC.METHODS:Two hundred two patients with UC were recruited from November 2012 to September 2018. The primary endpoint of this study was the maintaining time of the first and second courses of FMT. Relapse was defined as partial Mayo score ≥2 after achieving clinical remission and an increase of partial Mayo score ≥1 after achieving clinical response. The stool samples were analyzed by 16S rRNA gene sequencing.RESULTS:The median maintaining time of the efficacy was 120 days (IQR, 45–180) and 182.5 days (IQR, 105–311.25) from the first course and second course of FMT, respectively. No FMT-related serious adverse events were observed. The differences of the relative abundance in Eggerthella, Lactobacillus, and Ruminococcus between pre-FMT and 5 days post-FMT were remarkably correlated with the long-term clinical remission (P < 0.05).DISCUSSION:This study demonstrated that patients with UC should undergo the second course of FMT within 4 months after the first course of FMT for maintaining the long-term clinical benefits. The short-term alterations of microbiota after FMT may be conducive to predicting the long-term efficacy of FMT in UC (see Visual , Supplementary Digital Content, http://links.lww.com/CTG/A363).

Comparative of the Effectiveness and Safety of Biological Agents, Tofacitinib, and Fecal Microbiota Transplantation in Ulcerative Colitis: Systematic Review and Network Meta-Analysis

ABSTRACT Background: Biological agents are commonly used for the treatment of ulcerative colitis (UC). As new treatments, tofacitinib, and fecal microbiota transplantation (FMT) have demonstrated efficacy in treating UC. This network meta-analysis aims to determine the efficacy and safety of biological agents, tofacitinib, and FMT. Methods: A network meta-analysis was conducted by systematically searching the PubMed, Embase, and Cochrane Libraries. According to strict inclusion and exclusion criteria, we included randomized controlled trials (RCTs) of biological agents, tofacitinib, and FMT in UC. A random-effect model was chosen by the network meta-analysis and sensitivity analysis. Heterogeneity test and publication bias test were performed to determine the efficacy of treatments. Results: Data were extracted from 16 RCTs and we found that all treatments were more effective than the placebos. A total of 21 comparisons were made to determine efficiency. We found that infliximab, vedolizumab, and FMT performed better curative effect in terms of absolute effects and relative ranks. Furthermore, there was no statistical difference in the efficacy of biological agents, tofacitinib, and FMT. Moreover, no treatments were found to increase the occurrence of adverse events when compared with placebos, except infliximab. However, vedolizumab seemed to reduce the occurrence of adverse events compared with infliximab. Conclusion: Of the biological agents, vedolizumab and infliximab were the most effective, suggesting that biological agents are still a better choice. Nevertheless, tofacitinib and FMT may be promising alternatives with high efficacies. However, more safety and maintenance studies need to be conducted in future for the acquisition of more accurate results. Abbreviations: FMT: Fecal microbiota transplantation; UC: Ulcerative colitis; RCTs: Randomized controlled trials; IBD: Inflammatory bowel disease; CD: Crohn’s disease; IBS: Irritable bowel syndrome; CDI: Clostridium difficile infections; ITT: Intention-to-treat; RR: Relative risk; CI: Confidence interval; CrI: Credible intervals; IFX: Infliximab; ADA: Adalimumab; TFB: Tofacitinib; GLM: Golimumab; VDZ: Vedolizumab; PBO: Placebo; wk: week; F: Female; M: Male; AEs: Adverse events; SAEs: Serious adverse events; anti-TNF: Anti-tumor necrosis factors

Efficacy of intestinal microbiota transplantation in ulcerative colitis: a review of current literature and knowledge.

Inflammatory bowel disease (IBD) results in chronic inflammation in the intestine and is thought to arise from an abnormal immune response to host commensal bacteria. The current treatment paradigm for IBD is focused on suppression of the immune system. However, intestinal microbiota transplant (IMT) may present an avenue to treat IBD by altering the target of inflammation without necessitating immune suppression. Presently, reports of the greatest success with IMT in IBD have been with ulcerative colitis (UC). Four randomized controlled trials have evaluated the efficacy of IMT in UC and reported a pooled rate of combined clinical and endoscopic remission of 28% (95% CI: 4-10). For clinical remission alone, the pooled rate was as high as 42% with a number needed to treat of 5 (95% CI: 3-17). While promising, many questions remain which include elucidating the optimal microbiota enrichment, exacting donor profiling, and identifying the optimal IMT route and frequency. Longer follow-up is needed to determine the ability to achieve stable engraftment for maintenance of remission as well as safety of IMT therapeutics. This review will critically appraise the current literature for IMT in UC and identify key knowledge gaps.

Fecal microbiota transplantation for ulcerative colitis: a prospective clinical study

BackgroundFecal microbiota transplantation may contribute to disease remission in ulcerative colitis; however, the factors that determine the effects of treatment remain unknown. The aim of the present study was to prospectively investigate the clinical efficacy of fecal microbiota transplantation in patients with ulcerative colitis and identify the bacterial signatures associated with clinical remission.MethodsA total of 20 patients with ulcerative colitis were included in this prospective and uncontrolled study. All patients underwent gastroscopy five times, once every 3 weeks. Clinical indices were used to assess the efficacy of fecal microbiota transplantation, as well as the Mayo score, a score used to evaluate the extent of intestinal mucosal lesions in patients with ulcerative colitis. The changes in intestinal flora were detected by 16S ribosomal RNA-sequencing, and the relationship between ulcerative colitis and intestinal flora was analyzed.ResultsAfter treatment, clinical index scores for diarrhea, abdominal pain, and blood stool decreased significantly (p < 0.05). Erythrocyte sedimentation rate and C-reactive protein levels had not changed significantly; however, the clinical index score for intestinal mucosal lesions and the Mayo score decreased significantly. In addition, 16S ribosomal RNA-sequencing revealed that the intestinal flora in patients diagnosed with ulcerative colitis was different from that of donors.ConclusionFecal microbiota transplantation has a potential therapeutic value for the treatment of ulcerative colitis as it changes the abundance of bacterial flora and improves the scores for diarrhea, abdominal pain, and mucous membrane lesions in patients with this disease.Trial registrationThe clinical trial was retrospectively registered with ClinicalTrials.gov (NCT03016780) on January 11th, 2017.

Su1952 – Patients’ Perspective and Compliance Affect the Outcomes of Fecal Microbiota Transplantation for Ulcerative Colitis

Su1952 – Patients’ Perspective and Compliance Affect the Outcomes of Fecal Microbiota Transplantation for Ulcerative Colitis

Long-Term Safety and Efficacy of Fecal Microbiota Transplant in Active Ulcerative Colitis.

The therapeutic role of fecal microbiota transplantation in ulcerative colitis varies across different reports. This study aims to evaluate the long-term safety and efficacy of a strategy called step-up fecal microbiota transplantation for ulcerative colitis. Two clinical trials (NCT01790061, NCT02560727) for moderate-to-severe ulcerative colitis (Mayo score range 6-12) were performed from November 2012 to July 2017. Both studies were pooled for analysis on the safety and efficacy of fecal microbiota transplantation in patients with ulcerative colitis over a 1-year follow-up. The step-up fecal microbiota transplantation strategy included step 1: single fecal microbiota transplantation; step 2: two or more fecal microbiota transplantations; and step 3: fecal microbiota transplantations followed by immunosuppressants. Long-term clinical efficacy and adverse events were assessed, and multiple factors related to fecal microbiota transplantation were evaluated. Of 134 eligible patientsin this real-word study, 81.3% (109/134) were included for analysis. The follow-up ranged from 1 to 5years. Fecal microbiota transplantation-related adverse events were observed in 17.4% (43/247) of fecal microbiota transplantation procedures including one serious adverse event (myasthenia gravis) and 56 non-serious adverse events. Multivariable logistic regression analysis showed that both the method of preparation of microbiota from stool using the automatic system and the delivery method of colonic transendoscopic enteral tubing were associated with a lower rate of fecal microbiota transplantation-related adverse events (p = 0.023, p = 0.017, respectively). In total, 74.3% (81/109) and 51.4% (56/109) of patients achieved clinical response at 1month and 3months after step-up fecal microbiota transplantation, respectively. Fecal microbiota transplantation should be a safe and promising therapy for ulcerative colitis. The improved fecal microbiota preparation and colonic transendoscopic enteral tubing might reduce the rate of adverse events in ulcerative colitis. ClinicalTrials.gov NCT01790061, NCT02560727.