Safety Of Fecal Microbiota Transplantation Research Articles

First-line treatment of fecal microbiota transplantation for immune-mediated colitis.

2660 Background: The management of moderate to severe IMC includes immunosuppression with steroids and/or biologic agents. Long-term immunosuppression increases the risk for infections and steroid induced toxicities. Fecal microbiota transplantation (FMT) is increasingly used for the treatment of refractory IMC. Front-line FMT treatment has not been studied for IMC but could potentially alleviate IMC symptoms while reducing unnecessary extended exposure to steroids. In this study, we present a case series of 12 patients who received front-line FMT for the treatment of IMC as part of a clinical trial. Methods: This study reports preliminary data from a prospective clinical trial (NCT0403861) exploring the efficacy and safety of FMT as a first-line treatment for IMC. To be included, patients had to 1) have symptoms of immune-mediated diarrhea or colitis grade ≥ 2 (per Common Terminology Criteria for Adverse Events v5) within 45 days of FMT and 2) not have received any immunosuppressive treatment for IMC or any other indication around the time of FMT. Results: Twelve patients have been enrolled in the trial thus far. Patients received front-line FMT in a median of 31 days (IQR: 16-67 days) from IMC onset. 10 (83.3%) patients had symptom improvement in a median of 5 days (IQR: 1-7 days) after FMT. The only FMT-related adverse events reported were fatigue, transient fever, self-resolving abdominal cramping, and gassiness in six patients (50.0%) within the first week of FMT. One of the six patients additionally had recurrence of a previously existing frequent UTI due to bladder cancer within a week of FMT. Most patients (10, 83.3%) stopped immunotherapy due to IMC. Seven patients (63.6%) were able to resume cancer treatment after FMT, with four (33.3%) resuming checkpoint inhibitors. None of the patients that resumed ICI had recurrence of their colitis requiring immunosuppression. Nine patients (75%) had colitis remission by the end of the study period, with one additional patient showing signs of symptom improvement but passing away before his outcome could be assessed. Only two patients (16.7%) required immunosuppression for persistent colitis after FMT failure. Conclusions: This study is the first to evaluate the safety and efficacy of front-line FMT for the treatment of IMC. Our preliminary results are promising and show that FMT can be an effective first-line treatment for IMC that can quickly provide symptom relief in a majority of patients while avoiding the use of steroids. Our results also suggest that front-line FMT can be delivered in a timely manner and can allow for the safe resumption of immunotherapy in this population that typically responds well to immunotherapy. While more patients are needed before any solid conclusions may be drawn, there is mounting evidence to suggest that first-line FMT may be a safe and effective alternative to the current standard of care treatment for IMC. Clinical trial information: NCT04038619 .

Fecal microbiota transplantation: current challenges and future landscapes.

SUMMARYGiven the importance of gut microbial homeostasis in maintaining health, there has been considerable interest in developing innovative therapeutic strategies for restoring gut microbiota. One such approach, fecal microbiota transplantation (FMT), is the main "whole gut microbiome replacement" strategy and has been integrated into clinical practice guidelines for treating recurrent Clostridioides difficile infection (rCDI). Furthermore, the potential application of FMT in other indications such as inflammatory bowel disease (IBD), metabolic syndrome, and solid tumor malignancies is an area of intense interest and active research. However, the complex and variable nature of FMT makes it challenging to address its precise functionality and to assess clinical efficacy and safety in different disease contexts. In this review, we outline clinical applications, efficacy, durability, and safety of FMT and provide a comprehensive assessment of its procedural and administration aspects. The clinical applications of FMT in children and cancer immunotherapy are also described. We focus on data from human studies in IBD in contrast with rCDI to delineate the putative mechanisms of this treatment in IBD as a model, including colonization resistance and functional restoration through bacterial engraftment, modulating effects of virome/phageome, gut metabolome and host interactions, and immunoregulatory actions of FMT. Furthermore, we comprehensively review omics technologies, metagenomic approaches, and bioinformatics pipelines to characterize complex microbial communities and discuss their limitations. FMT regulatory challenges, ethical considerations, and pharmacomicrobiomics are also highlighted to shed light on future development of tailored microbiome-based therapeutics.

Efficacy and safety of fecal microbiota transplantation for chronic insomnia in adults: a real world study

ObjectiveTo assess the efficacy and safety of fecal microbiota transplantation (FMT) for adult chronic insomnia.MethodsPatients treated with FMT for chronic diseases were divided into chronic insomnia and non-insomnia group. The primary endpoint was the efficacy of FMT for insomnia 4 weeks after treatment, the secondary endpoints included the impacts of FMT on anxiety, depression, health-related quality of life, gut microbiota, and adverse events associated with FMT. Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI) were utilized to assess the efficacy of FMT on insomnia, self-rating anxiety/depression scale [Zung Self-Rating Anxiety Scale (SAS), Zung Self-Rating Depression Scale (SDS)] was employed to evaluate anxiety and depression. Quality of life was evaluated by SF-36. 16S rRNA sequencing was employed to analyze the gut microbiota and correlation analysis was performed.ResultsForty patients met the inclusion criteria and seven were excluded. 33 patients were enrolled and stratified into chronic insomnia group (N = 17) and non-insomnia group (N = 16). Compared to baseline, FMT significantly ameliorated the ISI (17.31 ± 5.12 vs. 5.38 ± 5.99), PSQI (14.56 ± 2.13 vs. 6.63 ± 4.67), SAS (54.25 ± 8.90 vs. 43.68 ± 10.64) and SDS (57.43 ± 10.96 vs. 50.68 ± 15.27) score and quality of life of chronic insomnia patients. 76.47% (13/17) of insomnia patients achieved the primary endpoints. In chronic insomnia patients, the relative abundance of Eggerthella marked enhanced at baseline, while the relative abundance of Lactobacillus, Bifidobacterium, Turicibacter, Anaerostipes, and Eisenbergiella significantly increased after FMT treatment, the latter positive correlated with the efficacy of FMT. Encouragingly, FMT also improved the sleep quality of non-insomnia patients.ConclusionEggerthella may potentially serve as a distinctive genus associated with chronic insomnia. FMT maybe a novel treatment option for adults with chronic insomnia and provide an alternative to traditional treatments for insomnia. The effects were positive correlated with the augmentation of probiotics, such as Bifidobacterium, Lactobacillus, Turicibacter, and Fusobacterium.

The gut microbiome dysbiosis and regulation by fecal microbiota transplantation: umbrella review.

Gut microbiome dysbiosis has been implicated in various gastrointestinal and extra-gastrointestinal diseases, but evidence on the efficacy and safety of fecal microbiota transplantation (FMT) for therapeutic indications remains unclear. The gutMDisorder database was used to summarize the associations between gut microbiome dysbiosis and diseases. We performed an umbrella review of published meta-analyses to determine the evidence synthesis on the efficacy and safety of FMT in treating various diseases. Our study was registered in PROSPERO (CRD42022301226). Gut microbiome dysbiosis was associated with 117 gastrointestinal and extra-gastrointestinal. Colorectal cancer was associated with 92 dysbiosis. Dysbiosis involving Firmicutes (phylum) was associated with 34 diseases. We identified 62 published meta-analyses of FMT. FMT was found to be effective for 13 diseases, with a 95.56% cure rate (95% CI: 93.88-97.05%) for recurrent Chloridoids difficile infection (rCDI). Evidence was high quality for rCDI and moderate to high quality for ulcerative colitis and Crohn's disease but low to very low quality for other diseases. Gut microbiome dysbiosis may be implicated in numerous diseases. Substantial evidence suggests FMT improves clinical outcomes for certain indications, but evidence quality varies greatly depending on the specific indication, route of administration, frequency of instillation, fecal preparation, and donor type. This variability should inform clinical, policy, and implementation decisions regarding FMT.

Efficacy and Safety of Fecal Microbiota Transplantation in the Treatment of Chronic Steroid-Refractory Graft-Versus-Host Disease after Hematopoietic Stem Cell Transplantation

Efficacy and safety of fecal microbiota transplantation in the treatment of chronic steroid-refractory graft-versus-host disease after hematopoietic stem cell transplantation Introduction The majority of patients who undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) with acute gut graft-versus-host disease has lost the diversity of gastrointestinal microbiota and associated to adverse clinical outcome. Despite glucocorticoids treatment has been considered as the first-line therapy regardless acute or chronic GVHD, the curative efficiency and durable response remains unsatisfactory. Several studies suggesting that fecal microbiota transplantation (FMT) from healthy donor effectively alleviated gut steroid-refractory acute GVHD (SR-aGVHD) by restoring diversity of gastrointestinal microbiota, resistance to potential pathogens, and transforming essential materials to metabolites for immunomodulating donor T cell which improved clinical outcomes in allo-HSCT. However, it is still unclear whether FMT therapy have similar potential efficacy in treating steroid-refractory chronic GVHD (SR-cGVHD). Here, we report the results of a pilot study from our single center using FMT from unrelated healthy donor to treat patients with SR-cGVHD. Method 12 patients aged 16-60 years with SR-cGVHD after allo-HSCT were enrolled. A total of 31 FMTs were performed via colonoscopy in 12 patients with SR-GvHD over three consecutive months. Adverse events with reasonable suspicion for being associated with FMT were monitored after treatment for 28 days. Partial response was defined as a decrease at least one stage in severity of GVHD or able to taper steroid dose. No response was defined as unable to taper steroid dose or need to increase or add immunosuppressor for controlling GVHD progression. CR was defined as the complete resolution of GVHD manifestations in all organs. To characterize the impact of the FMT on the gut microbiota, stool samples from recipients were collected the day before FMT treatment and 4 weeks after FMT treatment then carried out 16s rRNA sequencing. Result The overall response rate (ORR) in the patients with SR-cGvHD reached 50% (6/12), including CR in 0/0 (0%) cases and PR in 6/12 (50%). Most common adverse events were 3 abdominal bloating (9.68%), 2 diarrhea cases (6.45%) and 1 fever (3.23%). No serious adverse events were observed. The diversity of gastrointestinal microbiota remarkable decreased during SR-GVHD and it recovered after FMT (Figure B). After FMT treatment, similar α diversity of gastrointestinal microbiota in PR and NR patients was observed, whereas β-diversity analysis showed significant differences in the composition and abundance of the bacterial colonization between groups (Figure C and D). Conclusion The present study indicates that FMT as a new potential therapy in the treatment of SR-cGvHD is safe, well tolerated, and effective. Disclosures No relevant conflicts of interest to declare.

Long-Term Efficacy and Safety of Fecal Microbiota Transplantation for C. difficile Infections Across Academic and Private Clinical Settings.

Fecal microbiota transplant (FMT) is increasingly performed for Clostridioides difficile infection (CDI), although long-term efficacy and safety data are limited and are focused on results from academic medical centers rather than private settings where most patients receive care. Medical records of 165 patients who received FMTs for CDI were reviewed from an academic medical center and an adjacent, unaffiliated private practice. Of these patients, 68 also completed a survey regarding their long-term disease course and interval health. CDI resolution occurred in 81.3% (100/123) at the academic center and 95.2% (40/42) in the private setting. Private practice patients were more likely to present with recurrent, rather than refractory, CDI (92.9% vs. 66.7% P <0.001). Those from the academic center were more likely to have comorbid IBD, recent hospitalization, recent proton pump inhibitor use, ongoing immunosuppression, and inpatient FMT (all P values <0.05).Among surveyed patients, 29.4% developed interval comorbidities or changes to pre-existing conditions after a median follow-up of 33.7 months (IQR 13.2 to 44.3mo). Of 30 patients requiring subsequent antibiotics, 13.3% suffered CDI relapse. All subjects who had initially responded to FMT but had a subsequent CDI (17.9%, 10/56) responded to another FMT. In a real-world setting, patients who underwent FMT at academic centers differed significantly in clinical characteristics from those treated at a private practice. In both settings, FMT is an effective treatment for CDI not responding to standard therapies, even after subsequent antibiotic use. New diagnoses following FMT, however, are common and merit further exploration.

Assuring safety of fecal microbiota transplantation in the COVID-19 era: A single-center experience.

Fecal microbiota transplantation (FMT) is used to treat recurrent or refractory Clostridioides difficile infection (CDI). In the past, screening of fecal donors required surveillance of personal behavior, medical history, and diseases that could be transmitted by the blood or fecal-oral route. In addition, the exclusion of multidrug-resistant organisms (MDROs) has been recommended since 2018. This task has become more complicated in the era of the coronavirus disease-2019 (COVID-19) pandemic. To prevent fecal transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is crucial to commence screening for SARS-CoV-2, alongside other traditional tests. Our aim was to investigate whether hidden carriers of SARS-CoV-2 were enrolled for stool donation, and the status of the presence or incidence of MDRO during fecal donation in Taiwan. Fecal products collected from March 2019 to December 2022 were tested for MDRO and nucleic acid amplification tests for SARS-CoV-2 using the pooling method. The period of fecal product collection crossed the time before and during the COVID pandemic in Taiwan. A total of 151 fecal samples were collected. The fecal products were tested using polymerase chain reaction (PCR) to detect SARS-CoV-2. The results were negative for all stocks. This was similar to the results of MDRO testing. The safety of FMT products has been guaranteed during the pandemic. Our FMT center produced MDRO-free and COVID-19-free products before and during the COVID-19 outbreak in Taiwan. Our protocol was effective for ensuring the safety of FMT products.

Safety and feasibility of faecal microbiota transplantation for patients with Parkinson’s disease: a protocol for a self-controlled interventional donor-FMT pilot study

IntroductionExperimental studies suggest a role of gut microbiota in the pathophysiology of Parkinson’s disease (PD) via the gut–brain axis. The gut microbiota can also influence the metabolism of levodopa, which...

S234 Efficacy and Safety of Fecal Microbiota Transplant for First or Second Clostridioides difficile Infection: A Meta-Analysis of Randomized Controlled Trials

S234 Efficacy and Safety of Fecal Microbiota Transplant for First or Second Clostridioides difficile Infection: A Meta-Analysis of Randomized Controlled Trials

Unveiling the hidden world of gut health: Exploring cutting-edge research through visualizing randomized controlled trials on the gut microbiota.

The gut microbiota plays a crucial role in gastrointestinal and overall health. Randomized clinical trials (RCTs) play a crucial role in advancing our knowledge and evaluating the efficacy of therapeutic interventions targeting the gut microbiota. To conduct a comprehensive bibliometric analysis of the literature on RCTs involving the gut microbiota. Using bibliometric tools, a descriptive cross-sectional investigation was conducted on scholarly publications concentrated on RCTs related to gut microbiota, spanning the years 2003 to 2022. The study used VOSviewer version 1.6.9 to examine collaboration networks between different countries and evaluate the frequently employed terms in the titles and abstracts of the retrieved publications. The primary objective of this analysis was to identify key research areas and focal points associated with RCTs involving the gut microbiota. A total of 1061 relevant articles were identified from the 24758 research articles published between 2003 and 2022. The number of publications showed a notable increase over time, with a positive correlation (R2 = 0.978, P < 0.001). China (n = 276, 26.01%), the United States (n = 254, 23.94%), and the United Kingdom (n = 97, 9.14%) were the leading contributing countries. Københavns Universitet (n = 38, 3.58%) and Dankook University (n = 35, 3.30%) were the top active institutions. The co-occurrence analysis shows current gut microbiota research trends and important topics, such as obesity interventions targeting the gut microbiota, the efficacy and safety of fecal microbiota transplantation, and the effects of dietary interventions on humans. The study highlights the rapid growth and importance of research on RCTs that involve the gut microbiota. This study provides valuable insight into research trends, identifies key players, and outlines potential future directions in this field. Additionally, the co-occurrence analysis identified important topics that play a critical role in the advancement of science and provided insights into future research directions in this field.

Efficacy and safety of fecal microbiota transplantation in the treatment of ulcerative colitis: a systematic review and meta-analysis

To explore the efficacy and safety of fecal microbiota transplantation (FMT) as a treatment approach for ulcerative colitis (UC), a comprehensive systematic review and meta-analysis of randomized controlled trials was conducted. To collect and evaluate randomized controlled trials of high quality on FMT for UC, we searched a number of databases, including PubMed, Web of Science, Cochrane, Embase, and Medline, for studies published between the establishment of the databases and March 2023. We conducted a meta-analysis of the studies using Review Manager software (version 5.4.1) to determine the differences in rates of remission and adverse reactions between the FMT group and the control group, utilizing the risk ratio (RR) and 95% confidence interval (CI) to combine our findings. A total of 13 randomized controlled trials (RCTs) on the efficacy of FMT in patients with UC were included in the study, in which 580 patients participated, including 293 patients treated with FMT and 287 control subjects. Meta-analysis revealed that clinical remission was significantly better in the FMT group than in the control group [RR = 1.73; 95% CI = (1.41, 2.12); P < 0.00001]; endoscopic remission was significantly better in the FMT group than in the control group [RR = 1.74; 95% CI = (1.24, 2.44); P = 0.001]. Additionally, there were no significant differences in the incidence of adverse reactions between the two groups [RR = 1.00; 95% CI = (0.86, 1.15); P = 0.96]. Fecal microbiota transplantation has shown potential as a therapeutic intervention for inducing clinical remission in ulcerative colitis UC; nevertheless, the attainment of endoscopic remission and the maintenance of long-term remission continue to present challenges. Safety concerns persist throughout the treatment process, necessitating the implementation of measures to augment both safety and success rates.

High carriage rate of extended-spectrum β-lactamase Enterobacterales and diarrheagenic Escherichia coli in healthy donor screening for fecal microbiota transplantation.

The safety of fecal microbiota transplantation (FMT) has been highlighted by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli bacteremia transmitted from donors and acquisition of diarrheagenic E. coli (Shiga toxin-producing E. coli (STEC) and enteropathogenic E. coli (EPEC)) via FMT. The use of donor screening criteria to lower the risk of pathogen transmission via FMT is essential. This study aimed to demonstrate the outcomes of our strict donor screening program. This study was conducted at our FMT center between January 2019 and June 2022. Our donor screening program included an initial questionnaire and subsequent blood and stool testing. We further used selective culture for third-generation cephalosporin-resistant (3GCR) Enterobacterales and multiplex PCR to detect diarrheagenic E. coli in stools. The resistance mechanisms and sequence type of 3GCR Enterobacterales were determined. A total of 742 individuals were assessed, and 583 participants (78.6%) were excluded after questionnaire. Of the remaining 159 participants undergoing stool and blood tests, 37 participants were finally qualified (5.0%, 37/742). A high fecal carriage rate of ESBL-producing Enterobacterales (35.2%, 56/159), including E. coli (n=53) and Klebsiella pneumoniae (n=5), and diarrheagenic E. coli (31.4%, 50/159), including EPEC (n=41), enteroaggregative E. coli (n=11), enterotoxigenic E. coli (n=4), and STEC (n=1), was noted. CTX-M-79 and CTX-M-15 were dominant in E. coli and K. pneumoniae, respectively. The sequence types of the ESBL-producing strains were diverse. The screening for 3GCR Enterobacterales and diarrheagenic E. coli in stool is necessary. Our findings also support the effectiveness of multiplex PCR panels in FMT donor screening programs.

Faecal Microbiota Transplantation [FMT] in the Treatment of Chronic Refractory Pouchitis: A Systematic Review and Meta-analysis.

The aim of this systematic review and meta-analysis is to assess the efficacy and safety of faecal microbiota transplantation [FMT] in the treatment of chronic pouchitis. A PRISMA-compliant systematic review and meta-analysis was conducted using the following databases and clinical trial registers: Medline, Embase, Scopus, Cochrane Database of Systematic Reviews [CENTRAL], clinical trials.gov, ScienceDirect, and VHL [virtual health library]. The primary outcome was clinical response/remission in patients treated with FMT. Secondary outcomes included safety profile, quality of life, and changes in the gut microbiome. Seven observational cohort studies/case series and two randomised, controlled trials with a total of 103 patients were included. The route, preparation, and quantity of FMT administered varied among the included studies. Clinical response rate of 42.6% with a remission rate of 29.8% was estimated in our cohort following FMT therapy. Minor, self-limiting, adverse events were reported, and the treatment was well tolerated with good short- and long-term safety profiles. Successful FMT engraftment in recipients varied and, on average, microbial richness and diversity was lower in patients with pouchitis. In some instances, shifts with specific changes towards abundance of species, suggestive of a 'healthier' pouch microbiota, were observed following treatment with FMT. The evidence for FMT in the treatment of chronic pouchitis is sparse, which limits any recommendations being made for its use in clinical practice. Current evidence from low-quality studies suggests a variable clinical response and remission rate, but the treatment is well tolerated, with a good safety profile. This review emphasises the need for rationally designed, well-powered, randomised, placebo-controlled trials to understand the efficacy of FMT for the treatment of pouchitis.

First-line treatment of fecal microbiota transplantation for immune-mediated colitis.

2510 Background: The management of moderate to severe immune-mediated colitis (IMC) includes immunosuppression with steroids and/or biologic agents. Long-term immunosuppression increases the risk for infections and steroid side-effects. Fecal microbiota transplantation (FMT) is increasingly used for the treatment of refractory IMC but has not been studied in the front-line setting. Here we aim to test the hypothesis that front-line FMT can alleviate IMC symptoms while reducing unnecessary exposure to steroids and their complications. Methods: We will report interim data from a prospective clinical trial exploring the efficacy and safety of FMT as a first-line treatment for IMC. To be included, patients had to 1) have symptoms of immune-mediated diarrhea or colitis grade ≥ 2 within 45 days of FMT and 2) not have received any immunosuppressive treatment for IMC or any other indication around the time of FMT. Results: Seven patients have been enrolled in the trial thus far. Patients received front-line FMT within a median of 35 days (IQR: 18-57 days) from IMC onset. Five (71.4%) patients had symptom improvement within a median of 1 day (IQR: 1-5 days) after FMT. The only FMT-related adverse events reported were transient fever and self-resolving abdominal cramping in three patients (42.8%) within the first week of FMT. All patients stopped immunotherapy due to IMC. Six (85.7%) were able to resume cancer treatment after FMT with 4 patients (57.1%) resuming immunotherapy. Four patients (57.1%) had colitis remission by the end of the study period, with one additional patient showing signs of symptom improvement but passing away before IMC outcome could be assessed. Conclusions: This study is the first to evaluate the safety and efficacy of front-line FMT for the treatment of IMC. While more patients are needed before final conclusions can be drawn, our initial results suggest that FMT can be an effective first-line treatment for IMC that can be delivered in a timely manner and quickly provide symptom relief in a majority of patients while avoiding the use of steroids and allowing the safe resumption of immunotherapy. Therefore, first-line FMT may be a safe and effective steroid sparing alternative to the current standard of care treatment for IMC. Clinical trial information: NCT04038619 . [Table: see text]

Fecal Microbiota Transplant in Pediatric Solid Organ Transplant Recipients.

Fecal microbiota transplant (FMT) is an effective treatment for recurrent Clostridioides difficile infection (CDI). Safety concerns around FMT are increased in immunocompromised populations, such as solid organ transplant (SOT) recipients. Outcomes among adult SOT recipients suggest FMT is efficacious and safe; however, pediatric SOT data are lacking. We describe the efficacy and safety of FMT among pediatric SOT recipients in a single-center retrospective study from March 2016 to December 2019. Successful FMT was defined as no recurrence of CDI within 2 mo of FMT. We identified 6 SOT recipients ages 4-18 y who received FMT a median of 5.3 y post-SOT. Success after a single FMT was 83.3%. One liver recipient did not achieve cure after 3 FMTs and remains on low-dose vancomycin. One serious adverse event (SAE) occurred; cecal perforation and bacterial peritonitis occurred following colonoscopic FMT coordinated with intestinal biopsy in a kidney transplant recipient. He achieved full recovery and CDI cure. There were no other SAEs. There were no adverse events related to immunosuppression or transplantation status including: bacteremia, cytomegalovirus activation or reactivation, allograft rejection, or allograft loss. In this limited series, efficacy of FMT in pediatric SOT is comparable to efficacy in the general pediatric recurrent CDI population. There may be an increased risk of procedure-related SAE in SOT patients and larger cohort studies are needed.

Clinical study of 19 cases of steroid-refractory gastrointestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation with fecal microbiota transplantation

Objective: To investigate the clinical efficacy of fecal microbiota transplantation (FMT) for treating steroid-refractory gastrointestinal acute graft-versus-host disease (GI-aGVHD) . Methods: This analysis included 29 patients with hematology who developed steroid-refractory GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Huaian Hospital Affiliated to Xuzhou Medical University from March 2017 to March 2022. Among them, 19 patients underwent FMT treatment (the FMT group) and 10 patients did not (the control group). The efficacy and safety of FMT were assessed, as well as the changes in intestinal microbiota abundance, lymphocyte subpopulation ratio, peripheral blood inflammatory cytokines, and GVHD biomarkers before and after FMT treatment. Results: ① Complete remission of clinical symptoms after FMT was achieved by 13 (68.4%) patients and 2 (20.0%) controls, with a statistically significant difference (P<0.05). Intestinal microbiota diversity increased and gradually recovered to normal levels after FMT and FMT-related infections did not occur. ②The proportion of CD3(+) and CD8(+) cells in the FMT group after treatment decreased compared with the control group, and the ratio of CD4(+), regulatory T cells (Treg), and CD4(+)/CD8(+) cells increased (all P< 0.05). The interleukin (IL) -6 concentration in the FMT group was lower than that in the control group [4.15 (1.91-5.71) ng/L vs 6.82 (2.40-8.91) ng/L, P=0.040], and the IL-10 concentration in the FMT group was higher than that in the control group [12.11 (5.69-20.36) ng/L vs 7.51 (4.10-9.58) ng/L, P=0.024]. Islet-derived protein 3α (REG3α) was significantly increased in patients with GI-aGVHD, and the REG3α level in the FMT group was lower than that in the control group after treatment [30.70 (10.50-105.00) μg/L vs 74.35 (33.50-139.50) μg/L, P=0.021]. Conclusion: FMT is a safe and effective method for the treatment of steroid-refractory GI-aGVHD by restoring intestinal microbiota diversity, regulating inflammatory cytokines, and upregulating Treg cells.

Faecal microbiota transplantation to prevent complications after allogeneic stem cell transplantation for haematological malignancies: a study protocol for a randomised controlled phase-II trial (the FMT-allo study)

IntroductionAllogeneic haematopoietic stem-cell transplantation (allo-HSCT) is a major treatment for many haematological malignancies. The procedure has a good success rate but high transplant-related toxicity (TRM). TRM is mostly related to...

Fecal microbiota transplantation for induction of remission in Crohn's disease: a systematic review and meta-analysis.

Fecal microbiota transplantation (FMT) has been found to be a potential treatment for Crohn's disease (CD). We sought to perform a systematic review and meta-analysis to evaluate the efficacy and safety of FMT in CD. Electronic databases were searched for studies until January 2023. Clinical remission was established as the primary outcome. The secondary outcome was clinical response, endoscopic remission, minor adverse events, serious adverse events, and changes in disease activity indices, biochemical indicators, and microbial diversities. Pooled effect sizes and 95% confidence intervals (CIs) were calculated under the random effects model. Eleven cohort studies and one randomized controlled trial involving 228 patients were included. In a meta-analysis, the pooled proportion of adult patients with active CD that achieved clinical remission 2 to 4weeks after FMT was 57% (95% CI = 49-64%) with a low risk of heterogeneity (I2 = 37%). Furthermore, our results showed that FMT significantly (standardized mean difference = -0.66; 95% CI = -1.12 to -0.20; I2 = 0) reduced Crohn's disease activity index scores 4 to 8weeks after FMT. Subgroup analyses showed no difference between FMT methodologies, except for pre-FMT treatment with antibiotics (P = 0.02). Most adverse events were self-limiting and disappeared spontaneously within hours or days after FMT. Microbiota analysis showed an increased Shannon diversity and a shift toward donor-like microbiome after FMT. FMT could be a promising therapy in the short-term treatment of active CD. More placebo-controlled randomized trials with a long-term follow-up treatment are necessary. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022322694 No. CRD42022322694.

Fecal microbiota transplantation in Parkinson's disease-A randomized repeat-dose, placebo-controlled clinical pilot study.

The intestinal microbiome plays a primary role in the pathogenesis of neurodegenerative disorders and may provide an opportunity for disease modification. We performed a pilot clinical study looking at the safety of fecal microbiota transplantation (FMT), its effect on the microbiome, and improvement of symptoms in Parkinson's disease. This was a randomized, double-blind placebo-controlled pilot study, wherein orally administered lyophilized FMT product or matching placebo was given to 12 subjects with mild to moderate Parkinson's disease with constipation twice weekly for 12 weeks. Subjects were followed for safety and clinical improvement for 9 additional months (total study duration 12 months). Fecal microbiota transplantation caused non-severe transient upper gastrointestinal symptoms. One subject receiving FMT was diagnosed with unrelated metastatic cancer and was removed from the trial. Beta diversity (taxa) of the microbiome, was similar comparing placebo and FMT groups at baseline, however, for subjects randomized to FMT, it increased significantly at 6 weeks (p = 0.008) and 13 weeks (p = 0.0008). After treatment with FMT, proportions of selective families within the phylum Firmicutes increased significantly, while proportion of microbiota belonging to Proteobacteria were significantly reduced. Objective motor findings showed only temporary improvement while subjective symptom improvements were reported compared to baseline in the group receiving FMT. Constipation, gut transient times (NS), and gut motility index (p = 0.0374) were improved in the FMT group. Subjects with Parkinson's disease tolerated multi-dose-FMT, and experienced increased diversity of the intestinal microbiome that was associated with reduction in constipation and improved gut transit and intestinal motility. Fecal microbiota transplantation administration improved subjective motor and non-motor symptoms. ClinicalTrial.gov, identifier: NCT03671785.

Efficacy and safety of fecal microbiota transplantation via colonoscopy as add-on therapy in patients with mild-to-moderate ulcerative colitis: A randomized clinical trial.

Growing evidence supports the effectiveness of fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), although its effects seem to depend on the method of introduction, the number of procedures, the donor material, and the severity of UC. This study aimed to assess FMT's clinical and microbiological efficacy, tolerability, and safety in patients with mild-to-moderate UC. Patients with mild-to-moderate UC were randomized into two groups. The first group (standard-care, n = 27) was treated with basic therapy-mesalazine-at a daily dose of 3 g (2 g orally + 1 g rectally). In the second group (FMT group, n = 26), while taking mesalazine at the indicated dose, each patient with UC as add-on therapy underwent a single FMT procedure with fresh material delivered by colonoscopy from a healthy donor. The clinical efficacy of treatment in both groups was evaluated after 4 and 8 weeks. The primary outcome was remission of UC, defined as a partial Mayo score ≤2, and decreased fecal calprotectin. All patients underwent bacteriological examination of feces for quantitative microbiota composition changes. Clinical response in the form of a significant decrease in stool frequency and a tendency to normalize its consistency after 4 weeks was detected in 14 (51.9%) patients of the standard care group and 16 patients (61.5%) of the FMT group (p = 0.583). The Mayo score in the standard care group was 3.59 ± 1.21 and in the FMT group-3.15±1.04 (p=0.166). After 8 weeks, the main primary endpoint was achieved in 70.4% of the standard-care group patients as compared to 84.6% of participants who received FMT as add-on therapy (p = 0.215). A more pronounced decrease in Mayo score was observed in the FMT group compared to the standard-care group (1.34 ± 1.44 vs. 2.14 ± 1.4; p = 0.045). All patients also showed a significant decrease in fecal calprotectin levels, which correlated with clinical data, stool frequency, and clinical remission. An improvement in gut microbiota composition was noted in both groups, albeit it was significantly more pronounced in the FMT group. FTM in patients with mild-to-moderate UC is a well-tolerated, effective, and safe method of treatment in comparison to basic therapy. https://clinicaltrials.gov/ct2/show/NCT05538026?term=kobyliak&draw=2&rank=4, identifier: NCT05538026.