Fecal Microbiota Transplantation Procedure Research Articles

Evaluation of the Levels of Metabolites in Feces of Patients with Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn’s disease (CD), are chronic intestinal inflammatory disorders with only partially known etiology. They are characterized by chronic recurrent inflammation of the intestinal mucosa and lead to a significant decrease in the quality of life and death of patients. IBD is associated with suppression of normal intestinal microflora, particularly, a decrease in the number of bacteria—producers of short chain fatty acids (SCFAs) that exhibit anti-inflammatory and protective properties. Among various methods used for correction of intestinal microflora, fecal microbiota transplantation (FMT) attracts particular attention. FMT consists of the infusion of a fecal suspension from a healthy donor to the intestinal tract of a recipient patient. Such treatment is usually accompanied by a positive therapeutic effect with the restoration of the normal intestinal microflora of the recipient patient. A significant drawback of this method is the lack of standardization. Evaluation of metabolites produced by intestinal microflora, particularly, SCFAs, may be used for objective assessment of the functional state of the intestinal microbiota and, consequently, the success of the FMT procedure. Using gas chromatography and nuclear magnetic resonance spectroscopy, we have analyzed the concentrations and molar ratios of SCFAs from feces of 60 healthy donors. The results obtained by these two methods were in good accord with each other and with the published data. The analysis of SCFAs in the feces of patients with UC (19 patients) and CD (17 patients) revealed a general decrease in the concentration of SCFAs in the studied groups as compared with controls and significant fluctuations in the values of the studied group. Using limited sets of IBD patients (6 patients with UC and 5 patients with CD) we determined concentrations of SCFAs before and within 30 days of observation after FMT. In the selected time period, FMT exerts an effect on the SCFAs levels. Despite the fact that within 30 days of observation the SCFAs profiles, specifically attributed to healthy donors, have not been fully restored, the tendency to their achievement was clearly observed in both sets of UC and CD patients.

Efficacy and safety of fecal microbiota transplantationin patients with mild-to-moderate non-specific ulcerative colitis

Objective — to study the clinical and microbiological effectiveness, tolerability and safety of fecal microbiota transplantation (FMT) in patients with mild–to‑moderate nonspecific ulcerative colitis (NUC).Materials and methods. A single‑center, open, comparative, randomized clinical trial was conducted to study the effectiveness of FMT in patients with active mild‑to‑moderate NUC. Examinations involved 56 patients (36 men and 20 women) aged 22 to 48 years (mean age 32 ± 12 years) with verified mild‑to‑moderate NUC in the active phase. The severity of the NUC course and the degree of its activity was assessed based on the criteria of Truelove and Witt, as well as the endoscopic index of the NUC severity, the number of points on the Mayo scale and the level of fecal calprotectin. Depending on the treatment, all patients with NUC were randomized into 2 groups with the use of a computer random number method in a ratio of 1 : 1. Group I patients (10 women, 18 men) received basic mesalazine therapy in a daily dose of 3 g (2 g orally + 1 g rectally). In the second group, at baseline and against the background of mesalazine administration in the specified dose, each patient with NUC (19 men, 9 women) was undergone a single FMT procedure in which fecal material from a healthy superdonor was used. From them, fresh material was used in 14 cases and in 14 cases material was the frozen up to –80 ° С. Assessment of the clinical effectiveness of treatment in both groups was carried out after 4 and 8 weeks. An incomplete Mayo scale was used to assess the achievement of clinical remission, and fecal calprotectin levels were also studied. Besides, in all patients, before and 1 month after the treatment, the study of intestinal microbiome (IM) was performed at the level of the main microbial phylotypes by determining the DNA of Firmicutes, Bacteroidetes and Actinobacteria, as well as Faecalibacterium prausnitzii in fecal samples using quantitative polymerase chain reaction in real time.Results. The performance of a single FMT allowed to improve the results of the NUC basic treatment of with mesalazine, which manifested itself in the form of a significantly higher number of patients with clinical improvement after 4 weeks, a significantly lower number of patients requiring escalation of treatment, a significantly greater decrease in the Mayo index after 8 weeks, a significantly higher number of patients with clinical remission after 8 weeks. The fecal calprotectin level, despite a considerable decrease, in the specified time did not reach the norm, which indicates the need for prolongation of basic therapy. There were no serious adverse reactions to FMT, and mild adverse reactions were noted in 8 (28.6 %) patients. The clinical efficacy of treatment in both groups of patients was accompanied by an improvement in the state of IM (normalization of Bacteroidetes, an increase in the number of Firmicutes and Faecalibacterium prausnitzii, a decrease in the number of Actinobacteria) significantly more pronounced in the group of patients with NUC who were additionally treated with FMT.Conclusions. In a certain part of patients with mild‑to‑moderate NUC, even once performed FMT is a well‑tolerated and safe treatment method that promoted the increase of basic therapy effectiveness after 4 and 8 weeks, as well as significantly improved the condition of IM already 4 weeks after its implementation.

Factors Related to Outcomes of Fecal Microbiota Transplantation in Patients with Clostridioides difficile Infection

Background/AimsThe aim of this study was to evaluate factors related to outcomes of fecal microbiota transplantation (FMT) in patients with Clostridioides difficile infection (CDI) and viability of frozen stock for FMT.MethodsClinical data of patients who had received FMT for CDI were prospectively collected. Next-generation 16S rRNA gene sequencing of bacteria was performed from donors’ and recipients’ stool. Colony-forming units (CFUs) of cultures from frozen stock solutions for FMT were measured at 0, 4, 8, 12, 24, 48 weeks after preparation of the solutions.ResultsIn total, 25 FMT procedures were performed in 20 cases (14 fresh and 11 frozen FMT). Forty-five percent of cases involved fulminant CDI. The overall success rate was 55% after the 1st FMT and 75% after the 2nd FMT. The success rate was significantly higher in partially treated CDI than in refractory CDI (100% vs 71.4%; p=0.001). In successful cases only, the decrease in alpha-diversity in the recipient stool microbiomes was recovered after FMT to a level similar to that in donor stools. There was a significant difference in the microbiome composition in pre-FMT recipients’ stool between successful and failed cases (p=0.001). The CFUs of frozen solution for FMT did not decrease for 48 weeks in both aerobic and anaerobic cultures.ConclusionsFMT is highly effective in partially treated CDI but not in refractory CDI. The microbiome differs between failed and successful cases. Frozen stock for FMT is viable up to 48 weeks.

Donor fecal microbiota transplantation ameliorates intestinal graft-versus-host disease in allogeneic hematopoietic cell transplant recipients.

Disruption of the intestinal microbiota occurs frequently in allogeneic hematopoietic cell transplantation (allo-HCT) recipients and predisposes them to development of graft-versus-host disease (GvHD). In a prospective, single-center, single-arm study, we investigated the effect of donor fecal microbiota transplantation (FMT) on symptoms of steroid-refractory or steroid-dependent, acute or late-onset acute intestinal GvHD in 15 individuals who had undergone allo-HCT. Study participants received a fecal suspension from an unrelated healthy donor via nasoduodenal infusion. Donor FMT was well tolerated, and infection-related adverse events did not seem to be related to the FMT procedure. In 10 of 15 study participants, a complete clinical response was observed within 1 month after FMT, without additional interventions to alleviate GvHD symptoms. This response was accompanied by an increase in gut microbial α-diversity, a partial engraftment of donor bacterial species, and increased abundance of butyrate-producing bacteria, including Clostridiales and Blautia species. In 6 of the 10 responding donor FMT recipients, immunosuppressant drug therapy was successfully tapered. Durable remission of steroid-refractory or steroid-dependent GvHD after donor FMT was associated with improved survival at 24 weeks after donor FMT. This study highlights the potential of donor FMT as a treatment for steroid-refractory or steroid-dependent GvHD, but larger clinical trials are needed to confirm the safety and efficacy of this procedure.

Fecal microbiome change in patients with ulcerative colitis after fecal microbiota transplantation

Микробиота кишечника человека – это динамическая система, находящаяся под воздействием организма хозяина и внешних факторов. Возникающие нарушения кишечной микробиоты могут привести к патологическим состояниям, включая воспалительные и онкологические заболевания желудочно-кишечного тракта. Одним из возможных способов воздействия на микробиоту кишечника является фекотрансплантация (ФТ) – введение кишечной микробиоты от здорового донора в кишечный тракт пациента. В настоящее время в ряде стран этот метод используется для нормализации микробиоты кишечника, в основном при хронических воспалительных заболеваниях кишечника. В России (Новосибирск) уже несколько лет ведутся пилотные исследования эффективности ФТ при язвенном колите. Цель данной работы – оценить изменение микробиома кишечника 20 пациентов с язвенным колитом после однократного проведения ФТ. Основной метод – сравнительный анализ библиотек последовательностей 16S рибосомальной РНК, созданных на основе образцов, полученных от пациентов с язвенным колитом до и после ФТ и секвенированных на платформе Illumina MiSeq. Результаты исследования показали, что ФТ привела к увеличению среднего биоразнообразия последовательностей в образцах, полученных после ФТ, по сравнению с образцами, собранными до ФТ, хотя разница не была статистически достоверной. Доля последовательностей Firmicutes, являющихся доминирующей компонентой кишечной микробиоты здоровых людей, уменьшилась (~32 % vs. >70 %), а доля последова- тельностей Proteobacteria увеличилась (>9 % vs. <5 %). В некоторых образцах, собранных до ФТ, были обнаружены последовательности патогенных представителей Firmicutes и Proteobacteria, включая Acinetobacter spp., Enterococcus spp., Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus aureus, Stenotrophomonas maltophylia, Streptococcus spp. В большинстве случаев после ФТ доля таких последовательностей резко сократилась. Исключение составили последовательности Clostridium difficile, содержание которых в образцах почти половины пациентов составляло менее 0.5 %; после ФТ доля последовательностей C. difficile значительно уменьшилась лишь у трех пациентов. Следует отметить, что после ФТ повысилось на порядок содержание Lactobacillus spp. и существенно расширился их видовой состав. По результатам исследования можно сделать предварительное заключение о том, что даже однократная процедура ФТ приводит к повышению биоразнообразия микробиоты пациентов и оптимизации ее таксономического состава.

Evaluation of metabolites levels in feces of patients with inflammatory bowel diseases

Inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn's disease (CD), are chronic intestinal inflammatory disorders with an unknown etiology. They are characterized by chronic recurrent inflammation of the intestinal mucosa and lead to a significant decrease in the quality of life and death of patients. IBD are associated with suppression of normal intestinal microflora, including a decrease in bacteria, producers of short chain fatty acids (SCFAs), exhibiting anti-inflammatory and protective properties. Among the various methods of intestinal microflora correction, fecal microbiota transplantation (FMT), which engrafts the fecal microbiota from a healthy donor into a patient recipient, is of a particular interest. As a result, a positive therapeutic effect is observed, accompanied by the restoration of the normal intestinal microflora of the patient. A significant drawback of the method is the lack of standardization. Metabolites produced by intestinal microflora, namely SCFAs, allow objective assessment of the functional state of the intestinal microbiota and, consequently, the success of the FMT procedure. Using gas chromatography and nuclear magnetic resonance spectroscopy techniques, we have analyzed concentrations and molar ratios of SCFAs in fecal samples of 60 healthy donors. Results were in good accord when comparing two methods as well as with published data. Analysis of SCFAs in feces of patients with UC (19 patients) and CD (17 patients) revealed a general decrease in the concentration of fatty acids in the experimental groups with significant fluctuations in the values in experimental groups compared to control group of healthy donors. On the limited group of IBD patients (6 patients with UC and 5 patients with CD) concentration of SCFAs before and within 30 days of observation after FMT was determined. It was shown that FMT had a significant impact on the SCFAs levels within 1 month term; tendency to reach characteristics of healthy donors is unambiguously traced for both diseases.

Fecal Microbiota Transplantation As a Treatment of Severe Steroid-Resistant Acute and Chronic Graft Versus Host Disease. Spectrum of Responses and Complications

INTRODUCTION Only half of the patients with gut predominant acute graft-versus-host disease (aGvHD) respond to first-line treatment (corticosteroids). No consensus has yet been reached on treatment in the second and subsequent lines. There are several case reports supporting the role of fecal microbiota transplantation (FMT) in the treatment of steroid-resistant GvHD. Here we present the results of FMT in one of the largest cohorts of patients with acute (a) and chronic (c) GvHD, mostly with gut manifestation. MATERIAL AND METHODS 12 patients aged 26-67 years underwent a total of 15 FMTs to decolonize the gastrointestinal tract (GI) from antibiotic-resistant bacteria (ARB). In all of them steroid resistant GvHD (2 patients with cGvHD and 10 with aGvHD) coexisted. All patients with aGvHD had GI tract involvement (median grade: 3), 7 had skin (median grade: 3) and 5 had liver (median grade: 1) GvHD symptoms. Patients with cGvHD presented progressive involvement of the skin, lungs, pericardium and eyes. FMT was performed as two infusions by nasoduodenal tube of a 100g/200 ml solution of feces, on following days. OUTCOMES The median time from aGvHD diagnosis to the first FMT treatment was 46.5 days (8-489 days). Most patients were still on steroids during FMT (median dose 0.5 mg metyloprednisolone/kg of body weight). As a result, in 10/12 patients (83%) ARB decolonization was observed. Overall response rate (ORR) in the case of aGvHD reached 58% (7/12 performed FMTs), including CR in 4/12 (33%) cases. Median duration of response to relapse or death was 168 days (10-1080 days). The majority of patients who responded to FMT (5/6, 83%) underwent the procedure in a better general condition (ECOG≤2). Severe general condition (ECOG&gt; 2) seemed to be related with the presence of serious complications after FMT. Both patients with cGvHD achieved stabilization or improvement of organ disease, which may be related with FMT procedure (there is no data on use FMT in cGvHD). COMPLICATIONS Among the complications of FMT with a possible cause-effect relationship there were: 1 death in close relation with FMT (respiratory failure in the course of pneumonia), 3 septic episodes, 2 subileus episodes and one case of diarrhea. In the latter case, the workup revealed norovirus infection originating from the fecal material of the donor (who was asymptomatic). CONCLUSIONS The described results indicate that FMT may be an effective treatment option for severe GvH disease. Patients undergoing the procedure should be qualified early enough to avoid life-threatening complications and maximize the likelihood of responding to treatment. Figure Disclosures Jedrzejczak: Amgen: Consultancy, Other: travel support for hematology meetings (ASH, EBMT, EHA) ; Celgene: Other: travel support for hematology meetings (ASH, EBMT, EHA) ; Takeda: Consultancy; Novartis: Research Funding; Roche: Other: travel support for hematology meetings (ASH, EBMT, EHA) . Basak:Teva: Honoraria; Celgene: Honoraria.

Fecal Microbiota Transplantation After Oral Vancomycin for Recurrent Clostridium difficile Infection

Purpose Clostridium difficile infection (CDI) is one of the most common hospital-acquired infections in developed countries. Since 2000, there has been a significant increase in the incidence and severity of CDI. Treating recurrent CDI (rCDI) is challenging because the risk of recurrence increases with each subsequent episode. Several studies have demonstrated the benefit of fecal microbiota transplantation (FMT) in patients with rCDI with a cure rate ranging between 80% and 100%. The aims of this study were to review the FMT procedure and to identify the success rate of using 2-week oral vancomycin treatment before the FMT. Methods We performed a retrospective chart review for patients with rCDI who underwent an FMT procedure between 2014 and 2017. This study included patients who were diagnosed with rCDI and received 2-week oral vancomycin treatment before the FMT at Piedmont Columbus Regional Hospital. Results During the study period, 31 patients underwent 34 FMT procedures for rCDI. Twenty-nine patients were included in the study. Two patients (6.9%) had confirmed recurrence within 8 weeks after FMT, and 27 patients (93.1%) were considered treatment successes. No adverse events were noted. Both patients with FMT failures were offered treatment with a repeat FMT. Thirty-nine percent had mild to moderate rCDI. Most patients (69%) received upper FMT and 58.6% had fresh stool transplanted. Conclusions Fecal microbiota transplantation preceded by a standard 2-week vancomycin regimen for the treatment of patients with rCDI seems to be safe and effective. Further research is needed to explore optimal pretreatment regimens before the FMT to prevent FMT failure.

Fecal Microbiota Transplantation for Clostridium difficile Infection: A One-Center Experience

Background: Clostridium difficile is a gram-positive, anaerobic, and spore-forming bacillus, which is responsible for the majority of antibiotic-associated diarrhea and colitis. Objective: Determine if fecal microbiota transplantation (FMT) is effective in a population sample from Connecticut. Methods: We report the clinical experience of 92 consecutive patients from one gastroenterology practice in central Connecticut treated by colonoscopy with FMT for infection with Clostridium difficile from 2012 to 2017. The analyses are based on clinical follow-up up to 3 months after the FMT procedure and on medical chart review. Results: Overall, complete recovery occurred in 86% of patients. As previously reported in a limited number of previous studies, community-acquired cases were more common than hospital-acquired cases, and community-acquired cases were more likely to be female. Conclusions: Consistent with some previous reports, we found the following: the source of the donor for FMT did not make a difference in recovery: material from nonrelatives was as effective as from close relatives; and the presence of multiple comorbidities did not make a difference in recovery: patients with 2 or more comorbidities did as well as those with one or none.

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.

Safety of fecal microbiota transplantation in Chinese children: A single-center retrospective study.

BACKGROUNDFecal microbiota transplantation (FMT) is the administration of fecal bacterial liquid from healthy donors to a recipient’s digestive tract, which is recommended as a therapeutic method for recurrent Clostridium difficile infection (CDI). Many clinical trials focusing on different diseases are in progress. To date, scarce research and long-term follow-up have been conducted on FMT in children or on the proper guidelines. Our center first performed FMT to treat a 13-month-old boy with severe CDI in 2013. Until February 2018, our center had performed 114 pediatric FMT procedures in 49 subjects.AIMTo investigate the safety of FMT in children.METHODSA retrospective study was conducted on 49 patients who underwent 114 FMT treatments at our hospital. All FMT processes followed uniform standards. Adverse events (AEs) related to FMT were divided into short-term (48 h post-FMT) and long-term (3 mo). All potential influencing factors for AEs, such as gender, age, time of FMT infusion, route of administration, disease type, immune function state, and donor relative genetic background, were analyzed as independent factors. The significant independent factors and risk ratio with 95% confidence interval (CI) were assessed by multivariate logistic regression analysis.RESULTSForty-nine patients (mean age 68.1 mo, range 4 to 193 mo) were recruited. Their average follow-up time after the first FMT was 23.1 mo. The incidence of short-term AEs was 26.32% (30/114). The most common short-term AEs were abdominal pain, diarrhea, fever, and vomiting, which were all self-limited and symptom-free within 48 h. Two severe AEs occurred, and one patient died in the fourth week after FMT. All-cause mortality was 2.04%. As independent factors, age (P = 0.006) and immune state (P = 0.002) had significant effects. Age greater than 72 mo seemed to be correlated with more AEs than age 13 to 36 mo (P = 0.04). In multivariate logistic regression analysis, immune state was an independent risk factor for AE occurrence (P = 0.035), and the risk ratio in immunodeficient patients was 3.105 (95%CI: 1.080-8.923).CONCLUSIONAlthough FMT was proven to be tolerated in children, we need to be more cautious with immunodeficient patients. The effect on children’s long-term health is unpredictable.

Role of Fecal Microbiota Transplantation in Treating Inflammatory Bowel Disease and Clostridium difficile Infection: Narrative Review

Introduction: Fecal microbiota transplantation (FMT) is a therapeutic method where fecal microbiota from a healthy donor is transferred to a patient in the hopes of restoring normal, healthy microbiota of the gut. FMT is a promising treatment option for patients with medical conditions causing dysbiosis such as inflammatory bowel disease (IBD), Clostridium Difficile infection (CDI), metabolic syndrome, obesity, and irritable bowel syndrome. Over the years, studies were conducted to test its efficacy in other clinical conditions associated with normal bowel microbiome depletion. Methods: This narrative review summarizes the available efficacy and safety data on the use of FMT in IBD and C. diff patients. We completed an extensive literature search on PubMed, Google Scholar, Scopus, and Cochrane library electronic databases. Results: In most studies, patients received antibiotics before FMT. In studies retrieved, donors were related to recipients (relatives, friends, partners), whereas stool from unrelated donors was used less frequently. Pre-transplant screening procedures include serological testing for viruses (e.g., hepatitis A/B/C viruses, EBV, CMV, and HIV) and stool testing for C. difficile toxins, parasites, ova, and common bacterial enteropathogens. According to our search, several routes of administration were reported: enema, colonoscopy in seven studies, gastroscopy, nasojejunal tube, and nasogastric tube. Data support a positive effect of FMT on the outcome of IBD in at least some patients. In the majority of studies reviewed, IBD patients showed decreasing rates of remission/response over time. Our search shows FMT was well tolerated. Most common adverse events were abdominal pain, cramping, bloating, flatulence, increased stool frequency, and fever within days of transplant. The majority were self-resolving. Stool preparation is required for FMT with the minimum amount of stool infusate needed being 50g. Conclusion: Low recurrence rates of CDI and successful restoration of gut microbiota has proven FMT an innovative and popular treatment. Infectious Diseases Society of America and Society for Healthcare Epidemiology of America made updated guidelines in 2017 to recommend FMT for treatment of people with >2 recurrences of CDI despite standard antibiotic treatment. Successful FMT procedures can save the healthcare system thousands of dollars with fewer hospitalizations and frequent antibiotic prescriptions. Further studies focused on long-term outcomes and safety are also warranted.2745 Figure 1. Preparation of fecal materials for fecal microbiota transplantation.

Regional variability in fecal microbiota transplantation practices: a survey of the Southern Ontario Fecal Microbiota Transplantation Movement.

There is growing evidence that fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection, but little guidance exists for implementation of FMT programs. The objective of this study is to describe the program characteristics and protocols of 9 planned or operating FMT programs in the Southern Ontario Fecal Microbiota Transplantation (SOFT) Movement, to help guide future FMT program implementation. A 59-item survey was administered electronically to clinical leads of the SOFT Movement on June 2, 2016. The survey evaluated 7 domains: FMT program characteristics, FMT recipients, donor screening/selection, transplant manufacturing, FMT administration, good manufacturing procedures/biosafety procedures and infection-control procedures. We used descriptive statistics to analyze quantitative data. All 9 programs responded to the survey: 6 were active, 1 had FMT standard operating procedures developed but did not have clinical experience, and 2 were in the process of forming FMT programs. All 6 active programs performed FMT in adult patients with C. difficile infection. About 1300 FMT procedures were performed between 2003 and 2016. Five of the 6 operating programs administered the preparation via enema. Programs were driven primarily by physicians. All programs used universal FMT donors and followed Health Canada's screening guidelines, with considerable variability in screening frequency (every 3-6 mo) and modality. Locations for transplant preparation and manufacturing protocols varied across programs. Stool mass for FMT ranged from 20 g to 150 g, and transplant volume ranged from 25 mL to 300 mL. The experience of this high-volume regional FMT network highlights current challenges in FMT program development, including a high reliance on physicians and the costly nature of donor screening. Standardization and optimization through development of regional centres of excellence for FMT donor recruitment and administration should be explored.

An Intragastric Fecal Microbiota Transplantation Program for Treatment of Recurrent Clostridium difficile in Children is Efficacious, Safe, and Inexpensive

To assess the safety, efficacy, and relative expense of a nurse-led fecal microbiota transplantation (FMT) program for the treatment of recurrent Clostridium difficile infection (CDI). Retrospective cohort study design in children aged 1-18 years with recurrent CDI. The intervention was an intragastric FMT with stool derived from a donor stool bank. Primary outcome was resolution of diarrhea at 3 months post-transplantation. A secondary analysis compared charge data associated with FMT by intragastric delivery vs administration by colonoscopy or nasoduodenal tube. A total of 47 intragastric FMT procedures were performed in 42 children (median age 9 years) with recurrent CDI. Response to treatment varied by disease status, with 94% success in previously healthy children, 75% in medically complex children, and 54% in children with inflammatory bowel disease (P = .04). FMT via intragastric delivery showed lower facility and professional charges by 85% and 78% compared with delivery via colonoscopy and radiology-placed nasoduodenal tube, respectively. The use of stool derived from a donor stool bank decreased charges by 49% compared with charges associated with the use of a donor who was a relative. A nurse-led intragastric FMT procedure using stool derived from a donor stool bank is a relatively inexpensive and efficacious treatment for recurrent CDI in children. Intragastric FMT success in children was attenuated by the presence of underlying disease, particularly inflammatory bowel disease.

Treatment of Slow Transit Constipation With Fecal Microbiota Transplantation: A Pilot Study.

Fecal microbiota transplantation (FMT) has been proposed as a therapeutic approach for functional gastrointestinal disease. We launched a clinical study to examine the safety and efficacy of FMT for slow transit constipation (STC). Twenty-four patients with STC, aged from 20 to 74 were enrolled in this prospective open-label study. Patients received FMT on 3 consecutive days through nasojejunal tubes and followed up for 12 weeks after treatment. Rate of clinical improvement and remission, Wexner constipation scale, Bowel movement per week, and gastrointestinal quality-of-life index were evaluated. The rate of clinical improvement and remission based on clinical activity at week 12 was 50% (12/24) and 37.5% (9/24), respectively. The patient's stool frequency increased from a mean of 1.8 (SD 1.3) per week pre-FMT to 4.1 (SD 2.6) at week 12 post-FMT without laxative usage (P<0.01). The stool consistency showed a tendency to improve after FMT administration. Comparison of pre-FMT and post-FMT Wexner constipation scores demonstrated a significant reduction between baseline (14.1±3.3) and the first week (9.8±4.9), which was maintained up to the following 12 weeks (7.5±3.2; P<0.01). Compared with baseline, significant overall improvements were also seen in gastrointestinal quality-of-life index score at week 1, week 2, week 4, week 8, and week 12 of follow-up (P<0.01). The improvements were accompanied by the decline of colonic transit time. No severe adverse events during the whole FMT procedure follow-up except for venting (6/24), abdominal pain (3/24), bloating (2/24), and diarrhea (7/24). This is a pilot study demonstrating that FMT was safe and may have the potential to improve symptoms in patients with STC.

Outcomes, Safety and Predictors of Failure of Fecal Microbiota Transplantation for Refractory Clostridium difficile Infection

Introduction:Clostridium difficile infection (CDI) is a common cause of infectious diarrhea. The high rate of CDI recurrence (15-30%) after the initial episode is a major challenge. Fecal microbiota transplantation (FMT) is effective to treat antibiotic refractory CDI, with worldwide cure rates around 92%. Methods: This is a retrospective study to assess the efficacy, safety and predictors of failure of FMT in patients with refractory CDI. Patients who had first FMT via colonoscopy for refractory CDI between January 2013 and August 2015 were included. We collected demographics, comorbidities, symptoms, duration of CDI, treatment outcomes and complications from FMT. Logistic regression was used to demonstrate factors associated with FMT failure. Results: During our 32 month study period, 54 patients underwent FMT. Two patients were excluded due to loss of follow up. Females were 69% (36/52), mean age 54 years (range 18-96), mean CDI duration before FMT 17 months (range 2-75). Patients failed an average of 5 antibiotic courses (range 2-17) to treat CDI before FMT. Forty five (87%) stool donors were patients' family members. Mean follow up after FMT was 13 months (range 3-29). Forty five patients (87%) were successfully treated without CDI recurrence with just one FMT (Figure 1). Recurrent CDI despite FMT occurred in 7 patients (13%). Of these, 3 were successfully treated with oral vancomycin and 4 (8%) required second FMT. Of these 4, only one had recurrence of CDI despite second FMT due to antibiotic use. CDI cure rate at the end of the study was 98% (51/52). Diarrhea resolved immediately (within 3 days) in 56% (29/52) after FMT. One patient reported abdominal pain for 2 weeks related to the FMT procedure. No other adverse events were found. Six patients had recurrent diarrhea after FMT but tested negative for CDI. Logistic regression demonstrated that fluoroquinolone use (OR 7.7, p=0.02), and duration of disease before the first FMT of >18 months (OR 24, p=0.005) independently predicted FMT failure. Age ≥65, gender, inflammatory bowel disease, PPI use and number of antibiotic courses to treat CDI did not predict FMT failure. Patients with FMT failure were not immunosuppressed.Figure 1Conclusion: Our FMT experience matches the worldwide cure rates and supports emerging data about the safety and efficacy of FMT, with more than half of our patients showing immediate symptom relief. Fluoroquinolone use and longer duration of disease before the first FMT independently predicted FMT failure.

Inflammatory Bowel Disease Affects the Outcome of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection

A significant fraction of patients with recurrent Clostridium difficile infections (CDI) have inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) can break the cycle of CDI recurrence and can be performed without evaluation of the colon. We evaluated the efficacy of colonoscopic FMT in patients with and without IBD, and whether we could identify IBD in patients during this procedure. We collected clinical meta-data and colonoscopy results from 272 consecutive patients that underwent FMT for recurrent CDI at the University of Minnesota from 2008 through 2015. Patients had at least 2 spontaneous relapses of CDI following their initial episode and did not clear the infection after 1 extended antibiotic regimen. We collected random mucosal biopsies from patients' right colons to identify lymphocytic or collagenous colitis during the FMT procedure. Failure or success in clearing CDI was determined within or at 2 months after the FMT. Of patients undergoing FMT, 15% had established IBD and 2.6% were found to have IBD during the FMT procedure. A single colonoscopic FMT cleared CDI from 74.4% of patients with IBD and 92.1% of patients without IBD (P= .0018). Patients had similar responses to FMT regardless of immunosuppressive therapy. More than one-quarter of patients with IBD (25.6%) had a clinically significant flare of IBD after FMT. Lymphocytic colitis was documented in 7.4% of patients with endoscopically normal colon mucosa; only 3 of these patients (20%) required additional treatment for colitis after clearance of CDI. Based on an analysis of 272 patients, FMT is somewhat less effective in clearing recurrent CDI from patients with IBD, compared with patients without IBD, regardless of immunosuppressive therapy. More than 25% of patients with IBD have a disease flare following FMT. Lymphocytic colitis did not affect the outcome of FMT, but a small fraction of these patients required pharmacologic treatment after the procedure.

Dynamic changes in short- and long-term bacterial composition following fecal microbiota transplantation for recurrent Clostridium difficile infection.

BackgroundFecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI) that often fails standard antibiotic therapy. Despite its widespread recent use, however, little is known about the stability of the fecal microbiota following FMT.ResultsHere we report on short- and long-term changes and provide kinetic visualization of fecal microbiota composition in patients with multiply recurrent CDI that were refractory to antibiotic therapy and treated using FMT. Fecal samples were collected from four patients before and up to 151 days after FMT, with daily collections until 28 days and weekly collections until 84 days post-FMT. The composition of fecal bacteria was characterized using high throughput 16S rRNA gene sequence analysis, compared to microbiota across body sites in the Human Microbiome Project (HMP) database, and visualized in a movie-like, kinetic format. FMT resulted in rapid normalization of bacterial fecal sample composition from a markedly dysbiotic state to one representative of normal fecal microbiota. While the microbiome appeared most similar to the donor implant material 1 day post-FMT, the composition diverged variably at later time points. The donor microbiota composition also varied over time. However, both post-FMT and donor samples remained within the larger cloud of fecal microbiota characterized as healthy by the HMP.ConclusionsDynamic behavior is an intrinsic property of normal fecal microbiota and should be accounted for in comparing microbial communities among normal individuals and those with disease states. This also suggests that more frequent sample analyses are needed in order to properly assess success of FMT procedures.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-015-0070-0) contains supplementary material, which is available to authorized users.

Fecal microbiota transplantation for gastrointestinal diseases.

Fecal microbiota transplantation (FMT) is a treatment to restore the normal microbial composition of the gut by introducing fecal microbiota obtained from a healthy donor into a diseased individual. There has been a growing interest in the use of FMT as a treatment of various diseases including Clostridium difficile infection (CDI), inflammatory bowel disease, and irritable bowel syndrome. Despite the increasing application of FMT, there are no standard protocols. Many aspects of FMT procedures vary regarding donor selection, preparation of fecal materials, recipient preparation, and route of administration. FMT is most successful in treating recurrent CDI. A randomized controlled trial reported a success rate of approximaetly 90%. Ulcerative colitis (UC) is a potentially good indication for FMT, although limited evidence is available on the use of FMT for the treatment of UC. Only several small case series have been reported, and the results in terms of efficacy are inconsistent. FMT can also be used to treat diseases other than gastrointestinal disorders in which the gut microbiota is disturbed, e.g., cardiovascular diseases, autoimmune diseases, and metabolic disorders. There remain many unanswered questions with regard to FMT, and more research is required in this field.