In search of stool donors: a multicenter study of prior knowledge,perceptions, motivators,and deterrents among potential donors for fecal microbiota transplantation

ABSTRACT

Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection. Stool donors are essential, but difficult to recruit and retain. We aimed to identify factors influencing willingness to donate stool. This multi-center study with a 32-item questionnaire targeted young adults and health care workers via social media and university email lists in Edmonton and Kingston, Canada; London and Nottingham, England; and Indianapolis and Boston, USA. Items included baseline demographics and FMT knowledge and perception. Investigated motivators and deterrents included economic compensation, screening process, time commitment, and stool donation logistics. Logistic regression and linear regression models estimated associations of study variables with self-assessed willingness to donate stool. 802 respondents completed our questionnaire: 387 (48.3%) age 21-30 years, 573 (71.4%) female, 323 (40%) health care workers. Country of residence, age and occupation were not associated with willingness to donate stool. Factors increasing willingness to donate were: already a blood donor (OR 1.64), male, altruism, economic benefit, knowledge of how FMT can help patients (OR 1.32), and positive attitudes towards FMT (OR 1.39). Factors decreasing willingness to donate were: stool collection unpleasant (OR 0.92), screening process invasive (OR 0.92), higher stool donation frequency, negative social perception of stool, and logistics of collection/transporting feces. We conclude that 1) blood donors and males are more willing to consider stool donation; 2) altruism, economic compensation, and positive feedback are motivators; and 3) screening process, high donation frequency, logistics of collection/transporting feces, lack of public awareness, and negative social perception are deterrents. Considering these variables could maximize donor recruitment and retention.     

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.     

Effects of fecal microbiota transplantation in subjects with irritable bowel syndrome are mirrored by changes in gut microbiome

ABSTRACT

Irritable bowel syndrome (IBS) is a common disorder of the lower gastrointestinal tract. The pathophysiology is far from settled, but a gut microbial dysbiosis is hypothesized to be a contributing factor. We earlier published a randomized double-blind placebo-controlled clinical trial on fecal microbiota transplantation (FMT) for IBS – the REFIT trial. The present data set describes the engraftment and includes participants from the study who received active FMT; 14 participants with effect of FMT (Effect) and 8 without (No effect). Samples were collected at baseline, after 6 and 12 months. Samples from the transplants (Donor) served as a comparator. In total 66 recipient samples and 17 donor samples were subjected to deep metagenomic sequencing, and taxonomic and functional analyses were performed. Alpha diversity measures showed a significantly increased diversity and evenness in the IBS groups compared to the donors. Taxonomic profiles showed higher relative abundance of phylum Firmicutes, and lower relative abundance of phylum Bacteroidetes, compared to donors at baseline. This profile was shifted toward the donor profile following FMT. Imputed growth rates showed that the resulting growth pattern was a conglomerate of donor and recipient activity. Thirty-four functional subclasses showed distinct differences between baseline samples and donors, most of which were shifted toward a donor-like profile after FMT. All of these changes were less pronounced in the No effect group. We conclude that FMT induces long-term changes in gut microbiota, and these changes mirror the clinical effect of the treatment. The study was registered in ClinicalTrials.gov (NCT02154867).     

Clinical results and microbiota changes after faecal microbiota transplantation for chronic pouchitis: a pilot study

Abstract

Objectives: Research evidence suggests that chronic pouchitis is associated with intestinal dysbiosis. Faecal microbiota transplantation (FMT) has been proposed as a possible treatment. We performed a 6-month prospective, open-label, single-centre cohort pilot-study (NCT03538366) to investigate if FMT could improve clinical outcome and alter gut microbiota in patients with chronic pouchitis.

Materials and methods: Nine adult patients with chronic pouchitis were included and allocated to 14?days FMT by enemas from five faecal donors, with a 6-month follow-up. Pouchitis severity was assessed using pouchitis disease activity index (PDAI) before and after FMT. Changes in gut microbiota, and engraftment of donor’s microbiota were assessed in faecal samples.

Results: All patients were treated with FMT for 14 continuous days. Overall, four of nine patients receiving FMT were in clinical remission at 30-day follow-up, and three patients remained in remission until 6-month follow-up. Clinical symptoms of pouchitis improved significantly between inclusion and 14-day follow-up (p?=?.02), but there was no improvement in PDAI between inclusion (mean 8.6) and 30-day follow-up (mean 5.2). Treatment with FMT caused a substantial shift in microbiota and increased microbial diversity in six patients, resembling that of the donors, with a high engraftment of specific donor microbiota.

Conclusions: Symptomatic benefit in FMT treatment was found for four of nine patients with chronic pouchitis with increased microbial diversity and high engraftment of donor’s microbiota. A larger, randomised controlled study is required to fully evaluate the potential role of FMT in treating chronic pouchitis.     

Fecal microbiota transplantation for recurrent Clostridium difficile infection in hematopoietic stem cell transplant recipients

Recurrent Clostridium difficile infection (CDI) is a consequence of intestinal dysbiosis and is particularly common following hematopoietic stem cell transplantation (HSCT). Fecal microbiota transplantation (FMT) is an effective method of treating CDI by correcting intestinal dysbiosis by passive transfer of healthy donor microflora. FMT has not been widely used in immunocompromised patients, including HSCT recipients, owing to concern for donor‐derived infection. Here, we describe initial results of an FMT program for CDI at a US HSCT center. Seven HSCT recipients underwent FMT between February 2015 and February 2016. Mean time post HSCT was 635 days (25–75 interquartile range [IQR] 38–791). Five of the patients (71.4%) were on immunosuppressive therapy at FMT; 4 had required long‐term suppressive oral vancomycin therapy because of immediate recurrence after antibiotic cessation. Stool donors underwent comprehensive health and behavioral screening and laboratory testing of serum and stool for 32 potential pathogens. FMT was administered via the naso‐jejunal route in 6 of the 7 patients. Mean follow‐up was 265 days (IQR 51–288). Minor post‐FMT adverse effects included self‐limited bloating and urgency. One patient was suspected of having post‐FMT small intestinal bacterial overgrowth. No serious adverse events were noted and all‐cause mortality was 0%. Six of 7 (85.7%) patients had no recurrence; 1 patient recurred at day 156 post FMT after taking an oral antibiotic and required repeat FMT, after which no recurrence has occurred. Diarrhea was improved in all patients and 1 patient with gastrointestinal graft‐versus‐host disease was able to taper off systemic immunosuppression after FMT. With careful donor selection and laboratory screening, FMT appears to be a safe and effective therapy for CDI in HSCT patients and may confer additional benefits. Larger studies are necessary to confirm safety and efficacy and explore other possible effects.     

Problem of living liver donation in the absence of deceased liver transplantation program: Mansoura experience

We report our experience with potential donors for living donor liver transplantation (LDLT), which is the first report from an area where there is no legalized deceased donation program. This is a single center retrospective analysis of potential living donors (n = 1004) between May 2004 and December 2012. This report focuses on the analysis of causes, duration, cost, and various implications of donor exclusion (n = 792). Most of the transplant candidates (82.3%) had an experience with more than one excluded donor (median = 3). Some recipients travelled abroad for a deceased donor transplant (n = 12) and some died before finding a suitable donor (n = 14). The evaluation of an excluded donor is a time-consuming process (median = 3 d, range 1 d to 47 d). It is also a costly process with a median cost of approximately 70 USD (range 35 USD to 885 USD). From these results, living donor exclusion has negative implications on the patients and transplant program with ethical dilemmas and an economic impact. Many strategies are adopted by other centers to expand the donor pool; however, they are not all applicable in our locality. We conclude that an active legalized deceased donor transplantation program is necessary to overcome the shortage of available liver grafts in Egypt.     

Microbial composition analysis of Clostridium difficile infections in an ulcerative colitis patient treated with multiple fecal microbiota transplantations

Fecal microbiota transplantation (FMT) is a promising therapy for Clostridium difficile infection (CDI). However, questions remain regarding efficacy and safety in inflammatory bowel disease (IBD) patients, as well as longitudinal stability of donor stool composition. This report describes an IBD patient with two CDIs 18 months apart, each successfully treated with FMT with no IBD flares or complications. Microbiome composition analysis of patient samples during each infection revealed low-diversity microbiota patterns similar to those previously described in non-IBD patients with CDI and active IBD alone. Samples taken after each transplant demonstrated quick remodeling towards the donor's sample composition coinciding with symptom resolution. Of note, samples taken from the same donor 18 months apart reflected marked differences in microbiota abundances, suggesting that the use of single donors in FMT programs offers little benefit in ensuring predictability of donor stool composition over time. This report describes similar microbial composition patterns during CDI in IBD patients to those described previously in non-IBD patients, and supports FMT as safe and effective treatment for recurring CDI in this patient population.     

Fäkale Mikrobiotatransplantation (FMT)

Background

The human intestinal microbiome consists of about 100 trillion (10¹⁴) microorganisms and has important metabolic and immunological functions. The intestinal microbiome can be influenced by antibiotics, probiotics, dietary measures, and the relatively newly established method of fecal microbiota transplantation (FMT).

Fecal microbiome transfer

FMT comprises the transmission of fecal microorganisms of a healthy human donor into the gastrointestinal tract of a patient with the goal of establishing a normal microbiome in dysbiosis-associated diseases. The so far only indication for FMT that can be widely recommended is multiple recurrent Clostridium difficile infection (CDI). About 85?% of affected patients can be cured using FMT. Other possible therapeutic applications include chronic inflammatory and functional bowel diseases, nonalcoholic fatty liver disease, insulin resistance, morbid obesity, multiple sclerosis, or idiopathic thrombocytopenic purpura. These indications must be further examined in clinical trials; however, it has already been shown that the very good therapeutic success of FMT in patients with recurrent CDI cannot be readily transferred to other indications. Knowledge about the optimal donor, the best dosage, and the most appropriate route of administration for successful FMT is still incomplete. Essential is careful donor selection through accurate history, clinical examination, serology, and stool tests. The implementation of FMT in Germany is subject to the Medicines Act (Arzneimittelgesetz, AMG) with duty of disclosure and personal application by the attending physician.

     

Successful treatment of fulminant Clostridioides difficile infection with emergent fecal microbiota transplantation in a patient with acute myeloid leukemia and prolonged,severe neutropenia

We present a patient with acute myeloid leukemia and prolonged, severe neutropenia who developed fulminant Clostridioides difficile infection refractory to medical therapy and was high‐risk for surgical intervention. He was treated with fecal microbiota transplantation (FMT) for life‐saving cure. The patient had subsequent clinical improvement, however, developed multidrug‐resistant Pseudomonas aeruginosa bacteremia 2 days post‐procedure. We describe subsequent investigation of this event that found this bacteremia was not related to the donor stool administered during FMT. This case adds to the literature that FMT could be considered in heavily immunocompromised patients with fulminant Clostridioides difficile infection where maximal medical therapy has been ineffective and surgery may carry an excessively high mortality risk.     

Scaling Safe Access to Fecal Microbiota Transplantation: Past,Present, and Future

Purpose of Review

Universal stool banks (USBs) have emerged as a potential model for scaling access to fecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI). In this review, we outline the historical barriers constraining access to FMT, the evidence on methods and outcomes of USBs, and potential future directions for expanding access.

Recent Findings

Key historical barriers to FMT access include regulatory uncertainty, operational complexity of sourcing screened donor material, and logistical challenges of delivering fresh treatment preparations. USBs have demonstrated that FMT can be delivered safely at scale by centralizing donor selection, material processing, and safety monitoring. More evidence is needed to optimize USB methods, including for donor screening, material processing, and novel delivery modalities.

Summary

USBs have catalyzed broad access to FMT in North America and Europe. Future directions include developing evidence regarding oral preparations, harmonizing guidelines, disseminating best practice protocols, establishing long-term safety profiles, and expanding access to geographic areas of unmet need

     

Stool donor recruitment – A one-year experience

Stool donors for fecal microbiota transference (FMT) should be rigorously screened to identify any disorder in health status. The success of our screening protocol to identify eligible donors in the last year and a half was evaluated and compared with the published literature.The target population was medical students who responded to 3 public calls to donate stools. Qualified donors brought stool samples to our lab.Out of the 110 students who responded to the call, 26 were enrolled as study donors and delivered at least one stool sample. The main reason for volunteer exclusion was body mass index (BMI) <18.5 kg/m² or >25 kg/m² (n = 11) and for the identification of ESBL Escherichia coli in feces (n = 3).Our success rate after the screening protocol was considered high. Understanding the incentives to participate is critical to the success of recruitment strategies as FMT is still a little-known practice for general population.     

Recomendaciones para la selección del donante para la transferencia de microbiota fecal. Documento de posicionamiento avalado por la Societat Catalana de Digestologia,la Societat Catalana de Malalties Infeccioses i Microbiologia Clínica y el grupo GEMBIOTA de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica

Fecal microbiota transplantation (FMT) is an effective and safe treatment to treat recurrent Clostridioides difficile infection. It is essential to make every effort to perform FMT rigorously and based on scientific knowledge. Selection of the fecal microbiota donor is a key point of the process to ensure recipient safety. It is necessary to have protocols of action that allow clinicians to act with the maximum guarantees and to minimize the risks of the procedure. For this reason, a multidisciplinary working group has been set up in Cataluña with the aim of establishing recommendations for the selection of the fecal microbiota donor.     

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.     

High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria

Fecal microbiota transplantation (FMT) is becoming a more widely used technology for treatment of recurrent Clostridum difficile infection (CDI). While previous treatments used fresh fecal slurries as a source of microbiota for FMT, we recently reported the successful use of standardized, partially purified and frozen fecal microbiota to treat CDI. Here we report that high-throughput 16S rRNA gene sequencing showed stable engraftment of gut microbiota following FMT using frozen fecal bacteria from a healthy donor. Similar bacterial taxa were found in post-transplantation samples obtained from the recipients and donor samples, but the relative abundance varied considerably between patients and time points. Post FMT samples from patients showed an increase in the abundance of Firmicutes and Bacteroidetes, representing 75–80% of the total sequence reads. Proteobacteria and Actinobacteria were less abundant (< 5%) than that found in patients prior to FMT. Post FMT samples from two patients were very similar to donor samples, with the Bacteroidetes phylum represented by a great abundance of members of the families Bacteroidaceae, Rikenellaceae and Porphyromonadaceae, and were largely comprised of Bacteroides, Alistipes and Parabacteroides genera. Members of the phylum Firmicutes were represented by Ruminococcaceae, Lachnospiraceae, Verrucomicrobiaceae and unclassified Clostridiales and members of the Firmicutes. One patient subsequently received antibiotics for an unrelated infection, resulting in an increase in the number of intestinal Proteobacteria, primarily Enterobacteriaceae. Our results demonstrate that frozen fecal microbiota from a healthy donor can be used to effectively treat recurrent CDI resulting in restoration of the structure of gut microbiota and clearing of Clostridum difficile.     

Interrupted Time Series Analysis of Donor Heart Use Before and After the 2018 UNOS Heart Allocation Policy Change

BackgroundDonor heart scarcity remains the fundamental barrier to increased transplant access. We examined whether 2018 United Network for Organ Sharing (UNOS) policy changes have had an impact on donor heart acceptance rates.Methods and ResultsWe performed an interrupted time series analysis in UNOS to evaluate for abrupt changes in donor heart-acceptance rates associated with the new policy. All adult donor offers were evaluated between 2015 and 2021 (n = 66,654 donors). Donor volumes and transplants increased during this period, but the donor acceptance rate declined significantly from 31% in quarter 3 of 2018 to 26% acceptance in quarter 3 of 2021 (slope change -0.4% per quarter; P < 0.001). We identified 2 trends associated with this decline: (1) a growing number of donors with high-risk features, and (2) decreased acceptance of donors with certain high-risk features in the new allocation system.ConclusionsHeart transplant volumes have increased in recent years as a result of increased donor volumes, but donor heart acceptance rates began decreasing under the current allocation system. Changes in the donor pool and acceptance patterns for certain donor-risk features may explain this shift and warrant further evaluation to maximize donor heart use.     

Limited engraftment of donor microbiome via one-time fecal microbial transplantation in treated HIV-infected individuals

Many HIV-infected individuals on antiretroviral therapy (ART) exhibit persistent systemic inflammation, which predicts morbidity and mortality. ART-treated subjects concurrently exhibit marked compositional alterations in the gut bacterial microbiota and the degree of dysbiosis correlates with systemic inflammation. Whether interventions to modulate the microbiome can affect systemic inflammation is unknown. An open-label fecal microbial transplantation (FMT) was delivered by colonoscopy to asymptomatic HIV-infected ART-suppressed individuals without antibiotic pre-treatment. Stool was assessed before and after FMT for engraftment of donor microbes, and peripheral blood was assayed for immune activation biomarkers. Six participants received FMT and 2 participants served as controls. No serious adverse effects occurred during 24 weeks of follow-up. At baseline, HIV-infected individuals exhibited microbiota profiles distinct from uninfected donors. During the 8 weeks post-FMT, recipients demonstrated partial engraftment of the donor microbiome (P < 0.05). Recipient microbiota remained significantly distant from donors, unlike that observed following FMT for treatment of C. difficile infection. Systemic inflammatory markers showed no significant change post-FMT. FMT was well-tolerated in ART-treated, HIV-infected individuals. Engraftment was detectable but modest, and appeared to be limited to specific bacterial taxa. Whether antibiotic conditioning can enhance engraftment and the capacity of microbiota to modulate inflammation remains to be investigated.     

Fecal microbiota transplantation for management of Clostridium difficile infection

The widespread use of antibiotics has led Clostridium difficile infection (CDI) to become a common problem with pronounced medical and economic effects. The recurrence of CDI after treatment with standard antibiotics is becoming more common with the emergence of more resistant strains of C. difficile. As CDI is an antibiotic-associated disease, further treatment with antibiotic is best avoided. As the gut flora is severely disturbed in CDI, approaches that restore the gut microbiota may become good alternative modes of CDI therapies. Fecal microbiota transplantation (FMT) is the procedure of transplantation of fecal bacteria from a healthy donor individual into a patient for restoration of the normal colonic flora. Thus, FMT helps in the eradication of C. difficile and resolution of clinical symptoms such as diarrhea, cramping, and urgency. Though this approach to treatment is not new, presently, it has become an alternative and promising way of combating infections. The procedure is not in regular use because of the time required to identify a suitable donor, the risk of introducing opportunistic pathogens, and a general patient aversion to the transplant. However, FMT is gaining popularity because of its success rate as a panacea for recurrent attacks of CDI and is being increasingly used in clinical practice. This review describes the rationale, the indications, the results, the techniques, the potential donors, the benefits as well as the complications of fecal microbiota instillation to CDI patients in order to restore the normal gut flora.     

Relationship of symptom duration and fecal bacteriotherapy in Clostridium difficile infection-pooled data analysis and a systematic review

Abstract

Objective. Clostridium difficle-associated infection (CDI) is usually treated with antibiotics; nevertheless, the infection has a high relapse rate. Case series and case reports using fecal microbiota transplant (FMT) for CDI show promising results. However, there are no large studies to provide evidence for the efficacy of this therapy. The aim of this pooled patient data meta-analysis was to determine the efficacy of FMT in CDI. Methods. We performed a literature search for FMT for CDI or pseudomembranous colitis. Individual patient data were obtained from each study. The primary endpoint was to assess the rate of diarrhea resolution. Secondary endpoints were to identify variables associated with treatment failure and side effects of therapy. Results. A total of 289 patients from 25 published articles who received FMT for CDI were included in the pooled data analysis. FMT had an overall success rate of 91.2%. On univariate analysis, shorter duration of symptoms before FMT (< 60 days) and gastroduodenal route of fecal instillation were associated with treatment failure. On multivariate regression analysis, shorter duration of symptoms (< 60 days) before the FMT (OR= 11.08; p = 0.0009) was associated with treatment failure. Reported adverse events following FMT were irritable bowel syndrome (n = 1), symptoms of mild enteritis (n = 3), and suspected peritonitis following the procedure (n = 1). Conclusion. FMT is a safe and effective treatment option for CDI. Shorter duration of symptoms (< 60 days) before administering FMT is associated with treatment failure.     

A retrospective evaluation of causes of exempting living liver donors in an Egyptian centre

Background and study aimsLiving-related liver transplantation has helped to solve the problem of shortage of deceased organ donors. However, studies showed significant donor complications occurring with adult living liver donation. This study aims at assessing different causes of exclusion of potent living donor transplantation in Egypt.Patients and methodsThe data of 158 living donors (corresponding to 50 consecutive transplanted cases) were retrospectively studied.ResultsOnly 50 donors were found to meet all the preoperative assessment criteria while 108 potential donors were excluded at various assessment steps. Majority of the excluded potential donors were due to anatomical variations (52/108) followed by hepatic steatosis (19/108) and positive hepatitis B or C virus serology (11/108). Regarding the anatomic variations, biliary anomalies were ranked as the first cause to exclude donors with the majority of them having the type C biliary variant. Portal vein variations were the second most common cause of exclusion due to portal vein trifurcation. Hepatic artery variations were detected in a lesser number of excluded donors. No donors were excluded for hepatic vein anomalies.ConclusionAnatomical variations are the most common causes to exempt living liver donors. Preoperative evaluation of anatomical variations, viral serology and hepatic steatosis plays the major role to accept or exclude the potential donors.