Efficacy Of Fecal Microbiota Transplantation Research Articles

Fecal Microbiota Transplantation: A Systematic Review of Therapeutic Potential, Preparation Techniques, and Delivery Methods Across Medical Conditions

Fecal microbiota transplantation (FMT) is revolutionizing the treatment of gastrointestinal disorders by leveraging the gut microbiome in innovative ways. This systematic review evaluates the clinical effectiveness and safety of FMT across various medical conditions, offering insights into its therapeutic potential and limitations. A comprehensive search of PubMed, Web of Science, Scopus, Embase, and ClinicalTrials.gov from January 2000 to December 2023 identified 97 relevant studies on FMT's efficacy, safety, and microbiome changes after eliminating duplicates. FMT has demonstrated high success rates, particularly in treating recurrent and refractory Clostridium difficile infections (CDI), with up to 90% effectiveness, establishing it as a primary treatment for antibiotic-resistant cases. FMT’s applications are expanding to inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease, as well as metabolic disorders and neuropsychiatric conditions. Remission rates for IBD range from 37-45%, with outcomes influenced by donor characteristics, stool preparation, and disease subtype. with mild, self-limiting side effects such as transient diarrhea and abdominal cramping. However, rare serious adverse events underscore the need for rigorous donor screening and standardized preparation protocols to mitigate risks. FMT’s ability to restore healthy gut flora highlights its promise in both gastrointestinal and systemic disease management. However, further research is essential to establish optimized procedures, standardized guidelines, and long-term safety data to facilitate its integration into mainstream medical practice.

Fecal microbiota transplantation against moderate-to-severe atopic dermatitis: A randomized, double-blind controlled explorer trial.

Fecal microbiota transplantation (FMT) is a novel treatment for inflammatory diseases. Herein, we assess its safety, efficacy, and immunological impact in patients with moderate-to-severe atopic dermatitis (AD). In this randomized, double-blind, placebo-controlled clinical trial, we performed the efficacy and safety assessment of FMT for moderate-to-severe adult patients with AD. All patients received FMT or placebo once a week for 3 weeks, in addition to their standard background treatments. Patients underwent disease severity assessments at weeks 0, 1, 2, 4, 8, 12, and 16, and blood and fecal samples were collected for immunologic analysis and metagenomic shotgun sequencing, respectively. Safety was monitored throughout the trial. Improvements in eczema area and severity index (EASI) scores and percentage of patients achieving EASI 50 (50% reduction in EASI score) were greater in patients treated with FMT than in placebo-treated patients. No serious adverse reactions occurred during the trial. FMT treatment decreased the Th2 and Th17 cell proportions among the peripheral blood mononuclear cells, and the levels of TNF-α, and total IgE in serum. By contrast, the expression levels of IL-12p70 and perforin on NK cells were increased. Moreover, FMT altered the abundance of species and functional pathways of the gut microbiota in the patients, especially the abundance of Megamonas funiformis and the pathway for 1,4-dihydroxy-6-naphthoate biosynthesis II. FMT was a safe and effective therapy in moderate-to-severe adult patients with AD; the treatment changed the gut microbiota compositions and functions.

Efficacy of Fecal Microbial Transplantation for Improving Symptoms of Irritable Bowel Syndrome - A Pilot Study for Voluntary Participants in Korea

Irritable bowel syndrome (IBS) is a chronic, intractable functional disease. It is inferred that fecal microbiota transplantation (FMT) may have favorable efficacy on IBS by gut microbial modification. The aim of this study was to investigate the efficacy of FMT for improving severity in patients with IBS. Patients who voluntarily wanted FMT were consecutively enrolled. The study subjects were classified by subtype of IBS by the ROME IV criteria. The IBS-symptom severity score (IBS-SSS) was used to evaluate the efficacy of FMT. The subjects completed a questionnaire at baseline week 0 and weeks 4, 12, and 24 after FMT. FMT was performed by esophagogastroduodenoscopy using frozen stock stool solution. If the follow-up IBS-SSS achieved less than 75 points, it was defined as remission. Adverse events were also gathered. Twenty-one subjects were included from October 2023 until July 2024. There were 7 patients with IBS-C, 10 patients with IBS-D, 2 patients with IBS-M, and 2 patients with IBS-U type. The mean SSS of the IBS-D group was 244.0±64.2, which was higher than IBS-C group (192.9±85.4). Alleviations in IBS-SSS after FMT were observed in 19 subjects (19/21, 90.5%) at week 4. At week 12, 71.4% (5/7) in the IBS-C group and 20.0% (2/10) in the IBS-D group achieved remission. The remission states were maintained up to week 24 and no serious adverse events were reported. FMT might be an effective treatment option for improving symptoms of mild to moderate IBS, especially IBS-C.

Safety and efficacy of fecal microbiota transplantation for viral diseases: A systematic review of clinical trials.

Gut microbiota play important roles in several diseases like viral infections. In this systematic review, our objective was to assess the efficacy and safety of fecal microbiota transplantation (FMT) in treating various viral diseases. We conducted searches on databases including PubMed, Web of Science, Scopus, and Google Scholar until November 2023. Clinical trials reported outcomes related to safety of FMT or its efficacy in patients with viral diseases were included. We excluded other types of studies that enrolled healthy individuals or patients with other disorders and did not use FMT. The assessment of bias risk was conducted using the National Institutes of Health (NIH) study quality evaluation tool. Eight studies with total 196 participants were included. Viral diseases were human immunodeficiency virus (HIV), hepatitis B, COVID-19 and Clostridioides difficile coinfection, and cytomegalovirus colitis. In hepatitis B cases, HBeAg clearance was significant in those received FMT (p<0.01), while it was not significant in another one (p = 0.19). A clinical response was noted in 37.5% of patients with cytomegalovirus colitis, with an equal percentage achieving clinical remission post-FMT. There was a significant reduction in Clostridioides difficile relapse rate in FMT group than controls in coinfection of Clostridioides difficile and COVID-19 (2.17% vs. 42.5%, p<0.05). In patients with HIV, partial engraftment of the donor microbiome and increases in alpha diversity were observed after FMT. No severe adverse events were reported. Most studies had fair or good qualities. Our findings revealed FMT as a promising, safe treatment for some viral diseases. It improved viral clearance, clinical outcomes, and inflammation. However, the varying responses and small sample sizes call for more trials on FMT in viral diseases.

The impact of small intestinal bacterial overgrowth on the efficacy of fecal microbiota transplantation in patients with chronic constipation.

Existing studies have rarely considered the impact of the small intestine's microbial state on the efficacy of fecal microbiota transplantation (FMT), nor have they extensively explored the effect of the small intestine's microbial state on the recovery of colonic motility. Therefore, this study investigates the influence of small intestinal bacterial overgrowth (SIBO) on the efficacy of FMT in treating constipation, specifically the impact of the microbial state of the small intestine on the restoration of colonic homeostasis, and consequently on the recovery of colonic motility.

Impact of Clinical and Pharmacological Parameters on Faecal Microbiota Transplantation Outcome in Clostridioides difficile Infections: Results of a 5-Year French National Survey.

Detailed comparative assessment of procedure-related factors associated with faecal microbiota transplantation (FMT) efficacy in Clostridioides difficile infection (CDI) is limited. We took advantage of the differences in procedures at the various French FMT centres to determine clinical and procedure-related factors associated with FMT success in CDI. We performed a nationwide retrospective multicentre cohort study. All FMTs performed within The French Faecal Transplant Group for CDI from 2018 to 2022 were included. Clinical data were collected retrospectively from recipient medical files, characteristics of stool transplant preparations were prospectively collected by each Pharmacy involved. Univariate and multivariate analyses were performed using Fisher's test and multiple logistic regression. Six hundred fifty-eight FMTs were performed for 617 patients in 17 centres. The overall efficacy of FMT was 84.3% (520/617), with 0.5% of severe adverse events possibly related to FMT (3/658). Forty-seven patients were treated at the first recurrence of CDI with a similar success rate (85.1%). Severe chronic kidney disease (CKD; OR: 2.18, 95%CI [1.20-3.88]), non-severe refractory CDI (OR: 15.35, [1.94-318.2]), the use of ≥ 80% glycerol (OR: 2.52, [1.11-5.67]), insufficient bowel cleansing (OR: 5.47, [1.57-20.03]) and partial FMT retention (OR: 9.97, [2.62-48.49]) were associated with CDI recurrence within 8 weeks. Conditions of transplant manufacturing, bowel cleansing, and a route of delivery tailored to the patient's characteristics are key factors in optimising FMT efficacy. FMT at first recurrence showed high success in real-life practice, whereas it had lower efficacy in severe CDI and non-severe refractory CDI.

Safety and efficacy assessment of fecal microbiota transplantation as an adjunctive treatment for IgA nephropathy: an exploratory clinical trial

To assess the safety and efficacy of fecal microbiota transplantation (FMT) as an adjunctive therapeutic intervention for IgA nephropathy (IgAN). Fifteen patients with IgA nephropathy were recruited based on inclusion and exclusion criteria and underwent FMT using enteric microbial capsules. Clinical indicators, intestinal microbiota and metabolomic profiles, as well as changes in serum immune cells and cytokines, were monitored before and after FMT. No severe adverse reactions were observed in the subjects. After FMT, there was a reduction in the 24-h urinary protein quantification in subjects. The relative abundances of Phocaeicola_vulgatus, Bacteroides_uniformis, Prevotella_copri, Phocaeicola_dorei, Bacteroides_ovatus, Bacteroides_xylanisolvens, Parabacteroides _distasonis, Bifidobacterium_pseudocatenulatum, Bacteroides_sp._HF-162, and Bifidobacterium_longum changed after FMT. In terms of intestinal metabolites, the levels of acylcarnitine18:0 (ACar.18:0), cotinine, N-arachidonoyl-L-serine, phosphatidylcholine (PC. (18:3e/22:6)), serotonin, and fumagillin showed significant changes. Flow cytometry analysis showed the absolute count of plasma B cells decreased in subjects, and this change correlated with alterations in the intestinal microbiota and metabolites. This study preliminarily evaluates the safety and efficacy of FMT in patients with IgAN. No significant adverse reactions were observed, and the administration of FMT alongside ACEI/ARB therapy was effective in reducing urinary protein levels in patients with IgAN, a process that may be associated with B-cell immunity.

S1183 Efficacy of Fecal Microbiota Transplantation in Chronic Pouchitis - A Systematic Review and Meta-Analysis

S1183 Efficacy of Fecal Microbiota Transplantation in Chronic Pouchitis - A Systematic Review and Meta-Analysis

Therapeutic Potential of Fecal Microbiota Transplantation in Type 2 Diabetes Mellitus: A Systematic Review.

Diabetes mellitus is a chronic metabolic disease characterized by insulin resistance and hyperglycemia. It can cause various complications, which result in significant morbidity and mortality. There are multiple treatment options available to combat this disease; however, despite this, the incidence of type 2 diabetes mellitus is continuously increasing. Some promising results have shown that dysbiosis has a role in the pathogenesis of type 2 diabetes mellitus and fecal microbiota transplantation (FMT) in animals; however, the usage of FMT in humans needs further clarification and review. We explored PubMed, Popline, and Cochrane Library to identify relevant papers. Eight articles were then finalized after screening and applying eligibility criteria. These articles explored the role of the therapeutic efficacy of FMT in insulin resistance and hyperglycemia. The studies showed that the FMT had a positive impact on managing hyperglycemia and insulin resistance, which is evident in the decline of blood glucose and HBA1c levels and the rise of insulin and C-peptides. In addition, FMT also helped to control other risk factors such as hyperlipidemia and blood pressure; however, the impact on weight loss is not convincing. FMT also influenced the levels of some microbiota, which could be involved in controlling hyperglycemia and insulin resistance. Due to limited control trials and study periods and the small sample size of diabetic patients, more research is needed to explore the impact of FMT in controlling type 2 diabetes mellitus.

Oral Fecal Microbiota Transplantation in Dogs with Tylosin-Responsive Enteropathy-A Proof-of-Concept Study.

A clinical trial was conducted to evaluate the effect of fecal microbiota transplantation (FMT) on the canine chronic enteropathy clinical activity index (CCECAI), fecal consistency, and microbiome of dogs with tylosin-responsive enteropathy (TRE). The trial consisted of four phases: (1) screening with discontinuation of tylosin for 4 weeks, (2) inclusion with re-introduction of tylosin for 3-7 days, (3) treatment with FMT/placebo for 4 weeks, and (4) post-treatment with follow-up for 4 weeks after treatment cessation. The study found that the treatment efficacy of FMT (71.4%) was slightly higher than that of placebo (50%), but this difference was not statistically significant due to underpowering. The most abundant bacterial species detected in the fecal microbiomes of dogs with TRE before FMT or placebo treatment were Blautia hansenii, Ruminococcus gnavus, Escherichia coli, Clostridium dakarense, Clostridium perfringens, Bacteroides vulgatus, and Faecalimonas umbilicata. After FMT, the microbiomes exhibited increases in Clostridium dakarense, Clostridium paraputrificum, and Butyricicoccus pullicaecorum. The microbiome alpha diversity of TRE dogs was lower when on tylosin treatment compared to healthy dogs, but it increased after treatment in both the FMT and placebo groups. Comparisons with the stool donor showed that, on average, 30.4% of donor strains were engrafted in FMT recipients, with the most common strains being several Blautia sp., Ruminococcus gnavus, unclassified Lachnoclostridium, Collinsella intestinalis, and Fournierella massiliensis.

Ulva lactuca polysaccharides combined with fecal microbiota transplantation ameliorated dextran sodium sulfate-induced colitis in C57BL/6J mice.

Fecal microbiota transplantation (FMT) of healthy donors improves ulcerative colitis (UC) patients by restoring the balance of the gut microbiota. However, donors vary in microbial diversity and composition, often resulting in weak or even ineffective FMT. Improving the efficacy of FMT through combination treatment has become a promising strategy. Ulva lactuca polysaccharides (ULP) have been found to benefit host health by regulating gut microbiota. The effect of the combination of ULP and FMT in ameliorating UC has not yet been evaluated. The present study found that supplementation with ULP combined with FMT showed better effects in ameliorating UC than supplementation with FMT alone. Results suggested that FMT or ULP combined with FMT alleviated the symptoms of UC in mice, as evidenced by prevention of body weight loss, improvement of disease activity index and protection of the intestinal mucus. Notably, ULP in combination with FMT was more effective than FMT in reducing levels of cytokines and related inflammatory enzymes. In addition, ULP combined with FMT effectively restored the dysbiosis induced by dextran sulfate sodium (DSS) and further enriched probiotics (such as Bifidobacterium). The production of short-chain fatty acids, especially acetic acid, was also significantly enriched by ULP combined with FMT. Supplementation of ULP combined with FMT could significantly ameliorate DSS-induced colitis in mice by inhibiting inflammation and restoring dysbiosis of gut microbiota. These results suggested that ULP combined with FMT has potential application in ameliorating UC. © 2024 Society of Chemical Industry.

Disentangle beneficial effects of strain engraftment after fecal microbiota transplantation in subjects with MetSyn.

Fecal Microbiota Transplantation (FMT) has emerged as a potential modality for mitigating microbiome-associated diseases. Despite this potential, the precise causal pathways by which specific gut microbiota strains induce remission remain inadequately elucidated. In this study, we aimed to discern the impact of engraftment of donor-infused strains on alterations in plasma metabolites, subsequently contributing to the amelioration of clinical parameters involved in subjects with metabolic syndrome (MetSyn) receiving an FMT. We observed that a higher fraction of donor strains engrafted in the recipient is correlated to a reduction in diastolic blood pressure and found specific strain associations through canonical correlation analysis. Integrating the metabolomics profile shows that engraftment of Collinsella aerofaciens and Fusocatenibacter saccharovorans was related to a reduction in 2-oxoarginine in plasma, which was subsequently correlated to a reduction in diastolic blood pressure. In conclusion, we applied a novel framework to elucidate on the complex and heterogenous FMT intervention, establishing a connection between engrafted microbiota and clinical outcome parameters. Our findings underscore the potential therapeutic efficacy of FMT in ameliorating MetSyn, demonstrating a potential contribution of microbial strain engraftment to the improvement of MetSyn via modulation of circulating metabolites.

Colonization of microbiota derived from Macaca fascicularis, Bama miniature pigs, beagle dogs, and C57BL/6J mice alleviates DSS-induced colitis in germ-free mice.

Fecal microbiota transplantation (FMT) is an innovative and promising treatment for inflammatory bowel disease (IBD), which is related to the capability of FMT to supply functional microorganisms to improve recipient gut health. Numerous studies have highlighted considerable variability in the efficacy of FMT interventions for IBD. Several factors, including the composition of the donor microorganisms, significantly affect the efficacy of FMT in the treatment of IBD. Consequently, identifying the functional microorganisms in the donor is crucial for enhancing the efficacy of FMT. To explore potential common anti-inflammatory bacteria with therapeutic implications for IBD, germ-free (GF) BALB/c mice were pre-colonized with fecal microbiota obtained from diverse donors, including Macaca fascicularis (MCC_FMT), Bama miniature pigs (BP_FMT), beagle dogs (BD_FMT), and C57BL/6 J mice (Mice_FMT). Subsequently, mice were treated with dextran sodium sulfate (DSS). As expected, the symptoms of colitis were alleviated by MCC_FMT, BP_FMT, BD_FMT, and Mice_FMT, as demonstrated by the prevention of an elevated disease activity index in mice. Additionally, the utilization of distinct donors protected the intestinal barrier and contributed to the regulation of cytokine homeostasis. Metagenomic sequencing data showed that the microbial community structure and dominant species were significantly different among the four groups, which may be linked to variations in the anti-inflammatory efficacy observed in the respective groups. Notably, Lactobacillus reuteri and Flavonifractor plautii were consistently present in all four groups. L. reuteri exhibited a significant negative correlation with IL-1β, and animal studies further confirmed its efficacy in alleviating IBD, suggesting the presence of common functional bacteria across different donors that exert anti-inflammatory effects. This study provides essential foundational data for the potential clinical applications of FMT.IMPORTANCEDespite variations in efficacy observed among donors, numerous studies have underscored the potential of fecal microbiota transplantation (FMT) for managing inflammatory bowel disease (IBD), indicating the presence of shared anti-IBD bacterial species. In the present study, the collective anti-inflammatory efficacy observed across all four donor groups prompted the identification of two common bacterial species using metagenomics. A significant negative correlation between Lactobacillus reuteri and IL-1β was revealed. Furthermore, mice gavaged with L. reuteri successfully managed the colitis challenge induced by dextran sodium sulfate (DSS), suggesting that L. reuteri may act as an efficacious bacterium mediating shared anti-inflammatory effects among variable donors. This finding highlights the utilization of variable donors to screen FMT core bacteria, which may be a novel strategy for developing FMT applications.

Impact of fecal microbiota transplantation in severe alcoholic hepatitis: A systematic review and meta-analysis.

Severe alcoholic hepatitis (SAH) is a serious condition with few treatments. By modifying the gut-liver axis, fecal microbiota transplantation (FMT) was proposed as a treatment for SAH. The purpose of this meta-analysis was to evaluate the efficacy of FMT versus the standard of care (SOC) in improving SAH patient survival rates. A thorough search of electronic databases was conducted till September 2023. The survival rates of SAH patients undergoing FMT versus SOC were compared. Using Review Manager 5.4, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The meta-analysis consisted of six studies with a total of 371 patients with SAH. Patients who received FMT had significantly higher survival rates at 1 and 3 months compared to those who received SOC, with pooled OR of 2.91 (95% CI: 1.56-5.42, P = 0.0008) and 3.07 (95% CI: 1.81-5.20, P < 0.0001), respectively. However, the survival advantage disappeared after 6 months (OR: 2.96, 95% CI: 0.99-8.85, P = 0.05) and 1 year of follow-up (OR: 1.81, 95% CI: 0.44-7.46, P = 0.41). This meta-analysis highlights the potential of FMT to significantly improve short-term survival rates in SAH patients. However, the survival benefit did not last 6-12 months. These findings call for additional research into the effectiveness of FMT over the long term, along with strategies for extending the survival benefit.

Efficacy and safety of fecal microbiota transplantation for treatment of ulcerative colitis: A post-consensus systematic review and meta-analysis.

Numerous studies have assessed the efficacy and safety of fecal microbiota transplantation (FMT) as a therapy for ulcerative colitis (UC). However, the treatment processes and outcomes of these studies vary. To evaluate the efficacy and safety of FMT for treating UC by conducting a systematic meta-analysis. The inclusion criteria involved reports of adult patients with UC treated with FMT, while studies that did not report clinical outcomes or that included patients with infection were excluded. Clinical remission (CR) and endoscopic remission (ER) were the primary and secondary outcomes, respectively. We included nine studies retrieved from five electronic databases. The FMT group had better CR than the control group [relative risk (RR) = 1.53; 95% confidence interval (CI): 1.19-1.94; P < 0.0008]. ER was statistically significantly different between the two groups (RR = 2.80; 95%CI: 1.93-4.05; P < 0.00001). Adverse events did not differ significantly between the two groups. FMT demonstrates favorable performance and safety; however, well-designed randomized clinical trials are still needed before the widespread use of FMT can be recommended. Furthermore, standardizing the FMT process is urgently needed for improved safety and efficacy.

Effects of Retrograde Colonic Enema-Based Fecal Microbiota Transplantation in the Treatment of Childhood Constipation: A Randomized, Double-Blind, Controlled Trial.

Management of intractable childhood constipation is still challenging. The efficacy of retrograde colonic enema (RCE) with fecal microbiota transplantation (FMT) in intractable childhood constipation has not been established, although both have demonstrated potential in gastrointestinal diseases. The aim of this study was to determine the safety and efficacy of RCE-based FMT in the treatment of intractable constipation in children. A randomized, double-blind, controlled trial with 110 children was conducted. The patients were randomly assigned to the FMT with RCE group or the placebo with RCE group. All participants received a daily RCE, followed by a 4-week FMT treatment (twice a week) and a 12-week follow-up period. Spontaneous bowel movements ≥ 3 per week were the main outcomes, and the risk ratio with 95% confidence interval (CI) was calculated. Changes in intestinal bacterial profile were analyzed by BOX-PCR-based DNA fingerprinting and sequencing. The adverse effects were assessed based on symptoms. At the end of the follow-up period, 22 patients (40.0%) in the FMT with RCE group and 10 patients (18.2%) in the placebo with RCE group had ≥ 3 spontaneous bowel movements per week (net difference = 21.8%, 95% CI: 13.2%-30.4%; risk ratio: 1.364, 95% CI: 1.063-1.749; P < 0.05). Both RCE and FMT enriched the intestinal bacterial diversity of patients with constipation. The adverse events were all mild self-limiting gastrointestinal symptoms. FMT enhances the efficacy of RCE, and the use of RCE-based FMT is a safe and effective method in the treatment of intractable constipation in children.

Current landscape of fecal microbiota transplantation in treating depression.

Depression, projected to be the predominant contributor to the global disease burden, is a complex condition with diverse symptoms including mood disturbances and cognitive impairments. Traditional treatments such as medication and psychotherapy often fall short, prompting the pursuit of alternative interventions. Recent research has highlighted the significant role of gut microbiota in mental health, influencing emotional and neural regulation. Fecal microbiota transplantation (FMT), the infusion of fecal matter from a healthy donor into the gut of a patient, emerges as a promising strategy to ameliorate depressive symptoms by restoring gut microbial balance. The microbial-gut-brain (MGB) axis represents a critical pathway through which to potentially rectify dysbiosis and modulate neuropsychiatric outcomes. Preclinical studies reveal that FMT can enhance neurochemicals and reduce inflammatory markers, thereby alleviating depressive behaviors. Moreover, FMT has shown promise in clinical settings, improving gastrointestinal symptoms and overall quality of life in patients with depression. The review highlights the role of the gut-brain axis in depression and the need for further research to validate the long-term safety and efficacy of FMT, identify specific therapeutic microbial strains, and develop targeted microbial modulation strategies. Advancing our understanding of FMT could revolutionize depression treatment, shifting the paradigm toward microbiome-targeting therapies.

Comparative Efficacy of Fecal Microbiota Transplantation in Treating Refractory or Recurrent Clostridioides difficile Infection among Patients with and without Inflammatory Bowel Disease: A Retrospective Cohort Study.

Clostridioides difficile infection (CDI) worsens inflammatory bowel disease (IBD) prognosis. While fecal microbiota transplantation (FMT) is effective for refractory or recurrent CDI (rrCDI), comparative success rates between IBD and non-IBD patients are scarce. This study addresses this gap. A retrospective cohort study was conducted at Chang Gung Memorial Hospital from April 2019 to October 2023. Patients receiving FMT for rrCDI were categorized into IBD and non-IBD groups. Baseline characteristics and outcomes were compared at one month and one year, with successful FMT defined as the resolution of diarrhea without CDI recurrence. The study included 88 patients: 30 with IBD and 58 without IBD. The IBD group was younger, with fewer comorbidities. Success rates at one month were similar between groups (IBD: 80.0% vs. non-IBD: 78.9%, p = 0.908), as were negative toxin tests (IBD: 83.3% vs. non-IBD: 63.8%, p = 0.174). One-year success rates (IBD: 70.0% vs. non-IBD: 67.6%, p = 0.857) and eradication rates (IBD: 94.4% vs. non-IBD: 73.9%, p = 0.112) were also similar. Poor bowel preparation predicted FMT failure at one month (OR = 0.23, p = 0.019). No safety issues were reported. FMT is a safe, effective treatment for rrCDI, demonstrating similar success rates in patients with and without IBD.

Fecal Microbiota Transplantation for Sleep Disturbance in Post-acute COVID-19 Syndrome

Background & AimsPost-acute COVID-19 syndrome (PACS) is associated with sleep disturbance but treatment options are limited. The aetiology of PACS may be secondary to alterations in the gut microbiome. Here, we report the efficacy of faecal microbiota transplantation (FMT) in alleviating post-COVID insomnia symptoms in a non-randomised, open-label prospective interventional study. MethodsBetween September 22, 2022 and May 22, 2023, we recruited 60 PACS patients with insomnia defined as Insomnia Severity Index (ISI) ≥ 8 and assigned them to the FMT group (FMT at weeks 0, 2, 4 and 8; n=30) or the control group (n=30). The primary outcome was clinical remission defined by an ISI of less than eight at 12 weeks. Secondary outcomes included changes in the Pittsburgh Sleep Quality Index (PSQI), Generalised Anxiety Disorder-7 scale (GAD-7), Epworth Sleepiness Scale (ESS), Multidimensional Fatigue Inventory (MFI), blood cortisol and melatonin, and gut microbiome analysis on metagenomic sequencing. ResultsAt week 12, more patients in the FMT than the control group had insomnia remission (37.9% vs 10.0%; p=0.018). The FMT group showed a decrease in ISI score (p<0.0001), PSQI (p<0.0001), GAD-7 (p=0.0019), ESS (p=0.0057) and blood cortisol concentration (p=0.035) from baseline to week 12, but there was no significant change in the control group. There was enrichment of bacteria such as Gemmiger formicilis and depletion of microbial pathways producing menaquinol derivatives after FMT. Gut microbiome profile resembled that of the donor in FMT responders but not in non-responders at week 12. There was no serious adverse event. ConclusionThis pilot study showed that FMT could be effective and safe in alleviating post-COVID insomnia and further clinical trials are warranted. ClinicalTrials.gov identifier: NCT05556733.

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 .