Fecal Microbiota Transplantation In Patients Research Articles

P350 Perceptions of faecal microbiota transplantation in patients with ulcerative colitis

Abstract Background Faecal microbiota transplantation (FMT) is widely being studied for its therapeutic efficacy for a variety of ailments. Despite its gaining popularity, there is a limited understanding of firsthand patient experiences. We explored perceptions of patients who chose to pursue FMT and patients who declined FMT in favour of conventional medications for the treatment of their ulcerative colitis (UC). Methods Using qualitative descriptive design, eligible patients were invited to participate in face-to-face semi-structured interviews before and after FMT treatment. Interviews were audiotaped, transcribed, and analysed using a thematic analysis. Results Main baseline themes across the FMT (n = 9) and non-FMT (n = 8) groups included: (i) knowledge of FMT, (ii) attitudes around FMT, and (iii) factors contributing to the decision to pursue FMT. Post-FMT themes included: (i) experiences with FMT, and (ii) perceived response to treatment. We found a poor general understanding of FMT across both cohorts, suggesting a need for improving patient education. Non-FMT patients were less likely to have heard or researched FMT in the past due to feelings of ‘it just sounds weird’. Similar concerns were found across both groups, including fear of transmissible infections, cost of experimental therapy, and aversion to stool. Expectations varied between the two groups, with feelings of hope and a sense of ‘last resort’ driving patients to pursue FMT. In contrast, the non-FMT cohort felt a need to further research FMT, explore other treatment options before committing to FMT, and were more likely to describe their disease activity as ‘not at the severe end’. This demonstrates that FMT may be perceived as a ‘last-ditch effort’. Despite initial aversion, the non-FMT group demonstrated an interest in learning more about FMT and felt more open to the possibility of pursuing FMT in the future. The FMT group was more likely to harbour a positive view of natural medicine and classify FMT as natural, while the non-FMT cohort expressed ‘I’m not really into the weird stuff’. Post-FMT, some patients expressed delight in the perceived changes in their symptoms, including improved quality of life, decreased urgency, and less concerns with accidents. Conclusion Our results suggest that important motivating factors for pursuing FMT are a perception of naturality and a sense of last resort. With improved education, FMT may pose an acceptable and tolerable treatment option for patients with UC.

P358 Predictors of response to faecal microbiota transplantation in patients with active ulcerative colitis

Abstract Background Faecal microbiota transplantation (FMT) has been shown to be effective for induction of remission in nearly 50% patients with active UC. At present, factors impacting the response to FMT in UC remain unclear. Methods Patients with active UC treated with FMT via colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22 between September 2015 and March 2019 were analysed. Response to FMT was defined as achievement of clinical remission (Mayo score ≤2, with each sub-score ≤ 1 and endoscopic subscore of 0) at week 22. Patient and disease characteristics and FMT-related factors, considered to affect response to FMT were evaluated in a multivariable logistic regression analysis to determine the predictors of response to FMT. A statistical model was subsequently developed for predicting the success of FMT. Results Out of 140 patients with active UC and treated with FMT [mean age 34.29 ± 11.51 years, 65.71% males (n = 92), mean total Mayo score 7.8 ± 2.26], 57 (40.71%) achieved clinical remission. Of the various factors analysed, disease extent E2 (OR 2.34, 95% CI 1.17–4.68, p = 0.016), endoscopic Mayo score 1 (OR 15.375, 95% CI 1.89–125.11, p = 0.011) or 2 (OR 2.12, 95% CI 1.06–4.25, p = 0.035) and number of FMT sessions ≥ 4 (OR 16.74, 95% CI 4.85–57.85, p < 0.001) were found to be associated with response to FMT. An estimated response score was developed and score ≥4 predicted response to FMT with an accuracy of 74.3% [sensitivity 64.79% (95% CI 52.54% to 75.76%); specificity 84.06% (95% CI 73.26% to 91.76%, AUROC 0.834)]. Conclusion Disease Extent E2, endoscopic mayo score 1 or 2, and number of FMT sessions ≥4 predict response to FMT in active UC. The prediction model has good discriminative power at identifying individuals likely to respond to FMT.

Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection in Patients With Multiple Comorbidities: Long-Term Safety and Efficacy Results From a Tertiary Care Community Hospital.

BackgroundCure rates of Clostridium difficile infection (CDI) with fecal microbiota transplant (FMT) have been promising. However, there is debate regarding success of FMT in patients with comorbidities.MethodsElectronic chart review was done to collect data on patients who underwent FMT from January 2015 to August 2017. Charts were analyzed in November 2018 with a median follow-up of 25.4 months (interquartile range 20 - 31 months).ResultsTwenty patients underwent FMT. The primary success rate at our institution was 90% and overall success rate was 100%. Six patients (43%) had FMT failure (two early and four late).ConclusionsThis case series is a description of our center’s initial experience with FMT for treatment of recurrent CDI. Our high success rate reiterates the efficacy and safety of FMT in this population including patients with comorbidities.

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

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...

Efficacy of Fecal Microbiota Transplant in Hematological Cancers Patients with Recurrent Clostridioides Difficile Infection: A Systemic Review and Meta-Analysis

Introduction: Fecal microbiota transplant (FMT) has been shown to be an effective treatment for recurrent Clostridioides difficile infection (CDI). Immunosuppression is one of the risk factors for CDI. However, most of the trials evaluating efficacy of FMT have excluded immunocompromised patients. Patients with hematological cancers represent a major class of immunocompromised patients. Hence, we performed a meta-analysis to evaluate the efficacy of FMT in patients with hematological cancer for the treatment of recurrent CDI. Methods: A systematic search of Medline, Embase, and Web of Science was performed from January 2000 up to December 2018. Articles included for meta-analysis were case series and case reports that assessed efficacy of FMT in hematological cancer patients were included. Study quality was assessed using the Newcastle-Ottawa scale. The main outcomes were pooled proportions of patients achieving cure after first FMT. The cure rate was defined as resolution of diarrhea without any recurrence. Results: 10 studies (5 case series and 5 case reports) were included in the analysis, making up 29 patients who underwent 38 total FMT procedures. The follow up period ranged from 1- 14 months. Of the included patients, 17 had leukemia, 10 had lymphoma and 2 patients had multiple myeloma and myelodysplastic syndrome each. 7 of these patients had undergone hematopoietic stem cell transplant. The pooled cure rate was 82% [confidence interval (CI) 67-94%] after 1 FMT with no heterogeneity (I2=0%). Minor publication bias was seen on visual inspection of funnel plot. FMT was generally well tolerated by these patients. No serious side effects were reported in any study. One of the studies reported death due to cardiac arrest 5 days after FMT which was thought to be unrelated to the procedure. Mild side effects including mild abdominal pain, transient diarrhea, fecal urgency, constipation and nausea were reported in 5 patients. Conclusion: Based on limited observational data, FMT seems to be an effective and safe modality for management of recurrent CDI in patients with hematological cancers. However, further prospective clinical trials are needed to establish its safety as a first line therapy for recurrent CDI in this population. Figure Disclosures Jamshed: Takeda Pharmaceutical: Honoraria. Khanna:Rebiotix, Inc: Research Funding; Probio Tech, LLC: Consultancy; Facile Therapeutics: Consultancy; Shire, Plc: Consultancy.

168 Fecal Microbiota Transplant in Graft-versus-Host Disease of the Intestines: A Comprehensive Pooled Analysis

INTRODUCTION: Graft versus host disease (GVHD) of the intestines is a feared complication after hematopoietic stem cell transplantation (HSCT), and carries high morbidity and mortality. Recently fecal microbiota transplant (FMT) has been explored as a treatment modality for intestinal GVHD. The aim of our study was to pool data from individual feasibility studies to explore the efficacy and safety of FMT for gut GVHD. METHODS: A systematic search was performed for studies in PubMed, Embase, Cochrane database and ClinicalTrials.gov. All studies that reported data on FMT in patients who had previously undergone HSCT were included. Two independent authors conducted the systematic search. Pooled analysis was conducted for safety and efficacy of FMT in HSCT patients. RESULTS: A total of 15 studies comprising a total of 99 patients reported FMT outcomes after HSCT. Indication of FMT was restoration of microbiome in 41, Clostridium difficile infection in 21, and intestinal GVHD in 37 patients. All studies were single center pilot trials. Five studies with 37 patients reported efficacy outcomes for intestinal GVHD. A total of 57 FMTs were performed. All patients had previously failed at least one immunosuppressant regimen. All patients were either steroid resistant or steroid dependent. Overall complete response rate of 62.1% was observed (23 patients). Three additional patients partially responded to FMT. Positive response was accompanied by a decrease in stool volumes and frequency in all patients; reduction in use of anti-motility agents, and cessation of total parenteral nutrition was observed in all responders. All studies reported successful tapering of immunosuppressant and steroid dosage. FMT was generally well tolerated. No treatment-related mortality was reported. Minor adverse events included abdominal pain, nausea, mucosal tears, and minor aspiration without sequelae. Serious adverse events included bleeding in one patient, and grade 3 abdominal pain in one patient (resolved within 24 hours of capsule ingestion). Infections were reported in three patients after FMT (two with bacteremia), but could not be attributed to FMT with certainty. CONCLUSION: FMT is a promising modality for management of intestinal GVHD and carries low morbidity. It appears to be safe and acceptable as a salvage therapy for intestinal GVHD based on the current limited data. The need to withhold antibiotics to allow persistent engraftment may prove challenging in this severely immunocompromised population.

Fecal microbiota transplantation for patients with refractory diarrhea after allogeneic hematopoietic stem cell transplantation

目的探讨粪菌移植治疗异基因造血干细胞移植后难治性腹泻的有效性及安全性。方法纳入4例行异基因造血干细胞移植后并发难治性腹泻急性白血病患者，其中难治性肠道感染1例、肠道急性移植物抗宿主病3例。每例患者经鼻空肠管注入粪菌1~2次，每次3.4~6.0 U，观察粪菌移植后的疗效与不良反应。结果4例患者中3例达到完全缓解（CR），1例稳定（SD）。不良反应包括低热、腹痛、腹泻，均为Ⅰ级。结论粪菌移植治疗异基因造血干细胞移植后难治性腹泻可取得较好疗效，不良反应可耐受。

837 Short Chain Fatty Acid Profiles Are Altered by Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease and Recurrent Clostridioides difficile Infection

INTRODUCTION: Recurrent C. difficile infection (rCDI) is a major challenge among patients with inflammatory bowel disease (IBD). Perturbation of microbiota-mediated metabolism of short chain fatty acids (SCFA) has been reported in IBD patients. Fecal microbiota transplantation (FMT), an established therapy for rCDI, alters gut microbiota composition, but effects on SCFA are unclear. Accordingly, this study assessed SCFA profiles in IBD patients with rCDI pre- and post-FMT. METHODS: This open-label, prospective, single-arm multi-center cohort study enrolled patients from 4 tertiary care centers. Patients with IBD and ≥2 episodes of CDI received a single colonoscopic FMT from a universal stool bank. The primary outcome was CDI recurrence up to week 8 defined as diarrhea and EIA-positive toxin testing for C. difficile. Stool for metabolomic profiling was collected pre-FMT and week 1, 8 and 12 weeks post-FMT. A targeted gas chromatography-mass spectrometry protocol was used for the identification and quantification of SCFA. SCFA concentrations were analyzed via univariate analysis, comparing groups (e.g. pre- vs post-FMT). RESULTS: 37 participants were enrolled, with mean age of 37.6 years (range 20-76) and primarily female (n = 21, 57%). 14 had Crohn’s disease (CD) (mean HBI = 6.4) and 23 had ulcerative colitis (UC) (mean Partial Mayo Score = 4.5). Mean baseline fecal calprotectin was 1804.8 +/- 2307.7 Overall, 3 participants (8%) experienced FMT failure with confirmed EIA-positive stool, and the there were no related serious adverse events. Among the nine SCFAs assessed, including two branched chain fatty acids (isovalerate and isobutyrate) most were significant altered by FMT, with rapid and sustained changes (with the exception of acetate, in which no change was appreciated) (Figure 1). Additionally, 2-hydroxybutyrate and lactate, two markers of metabolic stress, were significantly reduced after FMT. Furthermore, the baseline stool samples of those who went on to recur were compared to those who did not (Figure 2); though not significant, there was a trend towards reduced baseline levels for butyrate, propionate and caproate among those who recurred. CONCLUSION: To our knowledge, this is the largest prospective trial to assess the effect of FMT in patients with IBD-CDI. The data suggests the efficacy and safety profile is better than previous reports. SCFAs were increased significantly post-FMT, and may offer insight into mechanism of clinically efficacy seen in this study.

Fecal microbiota transplantation as an effective initial therapy for pancreatitis complicated with severe Clostridium difficile infection: A case report.

BACKGROUNDModerately severe acute pancreatitis (MSAP) is a critical form of acute pancreatitis that is related with high morbidity and mortality. Severe Clostridium difficile infection (sCDI) is a serious and rare nosocomial diarrheal complication, especially in MSAP patients. Fecal microbiota transplantation (FMT) is a highly effective treatment for refractory and recurrent CDI (rCDI). However, knowledge regarding the initial use of FMT in patients suffering from sCDI is limited.CASE SUMMARYHere, we report an MSAP patient complicated with sCDI who was treated by FMT as a first-line therapy. The patient was a 51-year-old man who suffered from diarrhea in his course of acute pancreatitis. An enzyme immunoassay was performed to detect toxins, and the result was positive for toxin-producing C. difficile and toxin B and negative for C. difficile ribotype 027. The colonoscopy revealed pseudomembranous colitis. Due to these findings, sCDI was our primary consideration. Because the patient provided informed consent for FMT treatment, we initially treated the patient by FMT rather than metronidazole. Diarrhea resolved within 5 d after FMT. The patient remained asymptomatic, and the follow-up colonoscopy performed 40 d after discharge showed a complete recovery. Our case is the first reported in China.CONCLUSIONThis case explores the possibilities of initially using FMT to treat severe CDI. Moreover, FMT may become a critical component of the treatment for severe CDI in MSAP patients.

Acceptability, tolerability, and safety of fecal microbiota transplantation in patients with active ulcerative colitis (AT&S Study).

Fecal microbiota transplantation (FMT) targets gut microbiome dysbiosis and is an emerging therapy for ulcerative colitis (UC). Although initial results with FMT in patients with active UC are encouraging, data regarding its acceptability, tolerability, and safety are scant. A retrospective analysis of patients with active UC (Mayo clinic score≥4), who received multisession FMT (at weeks 0, 2, 6, 10, 14, 18, and 22) via colonoscopy between June 2016 and June 2018, was performed. Patient acceptability, tolerability, and immediate and long-term safety of the therapy were assessed. Of the 129 patients with active UC who were offered FMT, 101 patients consented, giving acceptability of 78.3%. Fecal slurry retention time improved with each session (3.27±1.06h for the first session vs 5.12±0.5h for the seventh session). Abdominal discomfort, flatulence, abdominal distension, borborygmi, and low-grade fever (30.8%, 15.9%, 9.8%, 7.9%, and 7.6%, respectively) were the most common post-procedural short-term adverse events. Long-term adverse events included new-onset urticaria (n=2, 4.3%), arthritis/arthralgia (n=3, 6.5%), depression (n=1, 2.2%), partial sensorineural hearing loss (n=1, 2.2%), and allergic bronchitis (n=1, 2.2%). Thirteen (12.9%) patients dropped out because of adverse events. Fecal microbiota transplantation appears to be a safe and well-tolerated procedure, with good acceptability in patients with active UC.

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.

Fecal Microbiota Transplantation: a Future Therapeutic Option for Obesity/Diabetes?

The aim of this review is to summarize the current data available on the metabolic effects of fecal microbiota transplantation (FMT) including obesity and glucose metabolism in humans. Gut microbiota dysbiosis is a frequent characteristic observed in obesity and related metabolic diseases. Pieces of evidence mostly generated in mouse models suggest that rescuing this dysbiosis associates with improved metabolism. In humans, dietary or bariatric surgery interventions are often accompanied by complete or partial restoration of this dysbiosis together with weight reduction and metabolic amelioration. FMT is an interesting option to modify gut microbiota and has been associated with improved clinical outcomes, albeit only used in routine care for Clostridium difficile infection. However, there are only limited data on using FMT in the metabolic context. FMT from lean donors significantly improves insulin sensitivity in obese subjects with metabolic syndrome. However, there is a wide range of clinical responses. Interestingly in subjects with high microbial gene richness at baseline and when FMT donors that are metabolically compromised are used, no metabolic improvement is seen. Moreover, more studies evaluating the effect of FMT in patients with overt type 2 diabetes are warranted. Furthermore, interventions (in the receiver prior to FMT) aiming to enhance FMT response also need evaluation.

Clinical response to fecal microbiota transplantation in patients with diarrhea-predominant irritable bowel syndrome is associated with normalization of fecal microbiota composition and short-chain fatty acid levels

Objectives: Irritable bowel syndrome (IBS) may be associated with disturbances in gut microbiota composition and functions. We recently performed a study of fecal microbiota transplantation (FMT) in diarrhea-predominant IBS (IBS-D) and found that IBS symptoms improved and the gut microbiota profile changed following FMT. We now aimed to explore the effects of FMT on the gut microenvironment in further detail by using 16S rRNA sequencing for more extended microbiota profiling and analyzing bacterial fermentation products (SCFAs: short chain fatty acids).Materials and methods: The study included 13 patients (four females and nine males) with IBS-D according to Rome III criteria and 13 healthy donors. Freshly donated feces were administered into duodenum via gastroscopy. The patients completed symptom and quality of life (QoL) questionnaires and delivered feces before and 1, 3, 12 and 20/28 weeks after FMT. Microbiota analysis was performed by sequencing 16S rRNA gene with Illumina Miseq technology. Fecal concentrations of SCFAs were analyzed by vacuum distillation followed by gas chromatography.Results: Several gut microbiota taxa and SCFAs were significantly different in the patients at baseline compared to their donors. These differences normalized by the third week following FMT in parallel with significant improvement in symptoms and QoL. Responders had different gut microbiota profile and SCFAs than nonresponders. Significant correlations were found between the gut microenvironment and IBS symptoms. No adverse effects were reported.Conclusions: FMT restores alterations of the gut microenvironment in IBS-D patients during the first 3 weeks and improves their symptoms for up to 28 weeks.ClinicalTrials.gov ID: NCT03333291.Trial registration: ClinicalTrials.gov identifier: NCT03333291.

Efficacy and Safety of Fecal Microbiota Transplantation in Patients With Rheumatoid Arthritis Refractory to Methotrexate

Efficacy and Safety of Fecal Microbiota Transplantation in Patients With Rheumatoid Arthritis Refractory to Methotrexate

Su1977 – The Safety and Efficacy of Fecal Microbiota Transplantation in Patients with Graft Versus Host Disease

Su1977 – The Safety and Efficacy of Fecal Microbiota Transplantation in Patients with Graft Versus Host Disease

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.

P594 Predictors of non-response to repeated faecal microbiota transplantation in patients with therapy refractory ulcerative colitis

P594 Predictors of non-response to repeated faecal microbiota transplantation in patients with therapy refractory ulcerative colitis

Long-term Outcomes of Fecal Microbiota Transplantation in Patients With Cirrhosis

Long-term Outcomes of Fecal Microbiota Transplantation in Patients With Cirrhosis

Combined Endoscopic and Oral Fecal Microbiota Transplantation in Patients with Antibiotic-Dependent Pouchitis: Low Clinical Efficacy due to Low Donor Microbial Engraftment

Background and Objective: A significant number of pouch patients develop antibiotic-dependent pouchitis (ADP). Microbial dysbiosis is thought to be a major driver of clinical symptoms in ADP. The objective of this proof of concept study was to evaluate safety, efficacy, and donor microbial engraftment of an intensified fecal microbiota transplant (FMT) consisting of a single endoscopic FMT followed by daily oral FMT for 2 weeks in patients with ADP. Methods: We performed a prospective placebo-controlled double-blind FMT trial in patents with established ADP and planned to enroll 20 patients in this proof of concept study. In case of non-response, patients were offered an optional open label active FMT treatment. The endpoints were safety, clinical remission without need for antibiotics during 16 weeks of follow-up, quantitative changes of fecal calprotectin (FCP), and engraftment of donor FMT as determined by metagenomic sequencing of the V4 region of the 16S rRNA gene. Results: Due to a lower than expected clinical remission rate and low FMT engraftment, enrollment in the study was stopped prematurely after 6 patients were included. All 6 patients enrolled in the placebo-controlled portion failed to respond and needed antibiotic rescue therapy shortly after FMT. FCP increased in the majority of patients in the setting of relapse after FMT. In the active open label FMT extension study 1 out of 5 patients achieved antibiotic-free clinical remission. FMT engraftment after active FMT was observed only in this single patient, whereas engraftment of donor FMT occurred in none of the other patients receiving active FMT, paralleling the lack of clinical response. Conclusions: Low donor FMT engraftment resulted in low clinical efficacy of FMT in patients with ADP. Before embarking on larger clinical trials with FMT in patients with ADP or other forms of pouchitis, it is mandatory to explore approaches for superior FMT engraftment.

Specific Bacteria and Metabolites Associated With Response to Fecal Microbiota Transplantation in Patients With Ulcerative Colitis

Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis (UC). In a randomized controlled trial of FMT in patients with active UC, we aimed to identify bacterial taxonomic and functional factors associated with response to therapy. We performed a double-blind trial of 81 patients with active UC randomly assigned to groups that received an initial colonoscopic infusion and then intensive multidonor FMT or placebo enemas, 5 d/wk for 8 weeks. Patients in the FMT group received blended homogenized stool from 3-7 unrelated donors. Patients in the placebo group were eligible to receive open-label FMT after the double-blind study period. We collected 314 fecal samples from the patients at screening, every 4 weeks during treatment, and 8 weeks after the blinded or open-label FMT therapy. We also collected 160 large-bowel biopsy samples from the patients at study entry, at completion of 8 weeks of blinded therapy, and at the end of open-label FMT, if applicable. We analyzed 105 fecal samples from the 14 individual donors (n= 55), who in turn contributed to 21 multidonor batches (n= 50). Bacteria in colonic and fecal samples were analyzed by both 16S ribosomal RNA gene and transcript amplicon sequencing; 285 fecal samples were analyzed by shotgun metagenomics, and 60 fecal samples were analyzed for metabolome features. FMT increased microbial diversity and altered composition, based on analyses of colon and fecal samples collected before vs after FMT. Diversity was greater in fecal and colon samples collected before and after FMT treatment from patients who achieved remission compared with patients who did not. Patients in remission after FMT had enrichment of Eubacterium hallii and Roseburia inulivorans compared with patients who did not achieve remission after FMT and had increased levels of short-chain fatty acid biosynthesis and secondary bile acids. Patients who did not achieve remission had enrichment of Fusobacterium gonidiaformans, Sutterella wadsworthensis, and Escherichia species and increased levels of heme and lipopolysaccharide biosynthesis. Bacteroides in donor stool were associated with remission in patients receiving FMT, and Streptococcus species in donor stool was associated with no response to FMT. In an analysis of fecal and colonic mucosa samples from patients receiving FMT for active UC and stool samples from donors, we associated specific bacteria and metabolic pathways with induction of remission. These findings may be of value in the design of microbe-based therapies for UC. ClinicalTrials.gov, Number NCT01896635.