Efficacy Of Fecal Microbiota Transplantation Research Articles

Fecal microbiota transplants modulate the gut microbiome of a two-toed sloth (Choloepus didactylus).

The microbes inhabiting an animal's gastrointestinal tracts, collectively known as the gut microbiome, are vital to animal health and wellbeing. For animals experiencing gut distress or infection, modulation of the gut microbiome, for example, via fecal microbiota transplant (FMT), provides a possible disease prevention and treatment method. The beneficial microbes present in the donor's transplanted feces can help combat pathogens, assist in digestion, and rebalance the recipient's microbiota. Investigating the efficacy of FMTs in animal health is a crucial step toward improving management strategies for species under human care. We present a case study of the use of FMTs in a two-toed sloth experiencing abnormally large, clumped, and frequent stools. We used 16 S rRNA amplicon sequencing of fecal samples to (a) compare the microbiomes of the FMT donor, a healthy, cohoused conspecific, and the FMT recipient and (b) assess the influence of multiple rounds of FMTs on the recipient's microbiome and stool consistency and frequency over time. In response to the FMTs, we found that the recipient's microbiome showed trends toward increased diversity, shifted community composition, and altered membership that more resembled the community of the donor. FMT treatment was also associated with marked, yet temporary, alleviation of the recipient's abnormal bowel movements, suggesting a broader impact on gut health. Our results provide valuable preliminary evidence that FMT treatments can augment the recipient's gut microbiome, with potential implications for animal health and management.

Safety and Efficacy of Fecal Microbiota Transplant in Chronic Pouchitis-A Systematic Review With Meta-Analysis.

Pouchitis is the most common long-term complication after ileal-pouch anal anastomosis in patients with ulcerative colitis. We conducted a systematic review and meta-analysis evaluating the safety and efficacy of fecal microbiota transplant (FMT) in chronic antibiotic dependent and refractory pouchitis. Multiple databases were searched through April 2022 for studies that reported the efficacy and safety of FMT in patients with chronic pouchitis. Meta-analysis using random effects model was performed to calculate pooled rates. Eight studies with a total of 89 patients were included in our review, with 74 patients having received FMT and 15 patients having received placebo. The mean age ranged from 32.6 to 51.5 years. In patients that received FMT, the pooled rates of overall remission was (Pouchitis Disease Activity Index score < 7) 22% (95% CI, 9%-43%; I2, 29%), clinical remission was 20% (95% CI, 6%-49%; I2, 25%), clinical response rate was 42% (95% CI, 30%-54%; I2, 7%), and the relapse rate 60% (95% CI, 40%-77%, I2 16%) over the mean follow up of 4.67 months (range 1-12 months). The pooled proportion of patients with adverse events was 54% (95% CI, 21%-84%; I2, 73%). There were no serious adverse events or deaths. In patients with chronic pouchitis, FMT is safe though there are mixed results in terms of its long-term efficacy. Future Randomized Controlled Trials with larger sample sizes and greater standardization in terms of preparation, delivery, and length of treatment of FMT are needed to determine efficacy.

Efficacy of Faecal Microbiota Transplantation for the Treatment of Autism in Children: Meta-Analysis of Randomised Controlled Trials.

Evidence-based research methods were applied to assess the efficacy of faecal microbiota transplantation (FMT) for the treatment of autism in children. We searched the Chinese Biomedical Literature, CNKI, Wanfang, PubMed, Embase, Web of Science, and the Cochrane Library databases to collect randomised controlled trials on faecal microbiota transplantation for the treatment of autism in children. The search included studies published from the creation of the respective database to 5 April 2022. Literature screening, data extraction, and quality evaluation were implemented by three investigators according to the inclusion and exclusion criteria. The meta-analysis was performed using the RevMan 5.1 software. Nine studies with population-based subjects and four studies with animal-based subjects were included. Five papers were screened for the meta-analysis. The results showed that FMT markedly reduced Autism Behaviour Checklist (ABC) scores in children with autism spectrum disorder (weighted mean difference (WMD) = -14.96; 95% confidence intervals (CI), -21.68 to -8.24; P < 0.001; I 2 = 0%). FMT also reduced Childhood Autism Rating Scale (CARS) scores (WMD = -6.95; 95% CI, -8.76 to -5.14; P < 0.001; I 2 = 28.1%). Our results indicate that FMT can benefit children with autism by reducing ABC and CARS scores, but more high-quality studies are needed to verify these results.

Fecal microbiota transplant for treatment of diarrhea in adult hospitalized horses-111 cases (2013-2018).

Fecal microbiota transplant (FMT) is increasingly administered as part of the treatment of colitis in horses, yet there is little data as to its effectiveness. Retrospective evaluation of the effects of FMT on discharge status, fecal consistency, length of hospitalization, and improvement in clinical signs in horses hospitalized for diarrhea. Retrospective case-control study. Medical records of adult horses (>1 year old) that received at least one transfaunation treatment (2013-2018) in two referral hospitals were identified through a medical records database search. Medical records of contemporary adult horses with diarrhea who did not receive FMT at the same study centers were used as controls. Control horses had statistically significant shorter hospitalization [7 (1-21)] as compared to the transfaunation group [12 (3-31)] ( p = 0.0006). There were no significant differences between groups in the number of days to the improvement of feces (p = 0.38), or in days to normalization of fecal consistency (p = 0.43), respiratory rate (p = 0.42), heart rate (p = 0.27), body temperature (p = 0.12), peripheral white blood cell count (p = 0.37), improvement in appetite (p = 0.81), or attitude (p = 0.06). There was also no significant difference in survival to discharge (transfaunation 28/37, 75.7%; control 56/74, 75.7%, p = 1.0). There were no significant advantages of performing FMTs in horses with diarrhea in this retrospective study. This highlights the need for prospective, randomized studies to evaluate the efficacy of FMT, as well as different formulations, in horses with colitis before this can become standard practice.

2006. Long-term efficacy of lower-gastrointestinal delivery fecal microbiota transplantation for recurrent Clostridioides difficile infection

Abstract Background The rate of recurrent Clostridioides difficile infection (rCDI) is 15-28% for those that initially respond to antibiotics and increases to about 50% in those with more than two recurrences. Fecal microbiota transplantation (FMT) is a treatment option for patients that have failed antibiotics for at least two rCDIs or for those with severe or fulminant CDI refractory to antibiotics. Data assessing the long-term efficacy of FMT beyond 1 year are scarce. The objective of this study is to evaluate the long-term efficacy of lower-gastrointestinal (GI) delivery FMT in addition to standard of care pharmacotherapy (SOCp) for rCDI compared to patients that received SOCp alone. Methods This is a single center, retrospective cohort study that included patients 18-99 years old who received either SOCp or FMT in addition to SOCp for rCDI between January 1, 2018 and December 30, 2020. Exclusion criteria were pregnancy or receipt of upper-GI delivery FMT. The primary endpoint was rCDI within 12 months. Secondary endpoints were all-cause mortality at 6, 12, 18, and 24 months, recurrence at 6, 18, and 24 months, and time to first recurrence of CDI (months). Patients were propensity matched based on age, immunocompromised status, and antibiotic received for index rCDI episode. Results The rCDI rate at 12 months was 8% and 50% in the FMT (n = 24) and SOCp (n = 24) groups, respectively (p = 0.0001). The rCDI rate at 24 months was 8.3% and 50% in the FMT and SOCp groups, respectively (p=0.0015). Mean time to 1st rCDI episode was 15.5 and 1.5 months in the FMT and SOCp groups, respectively (p = 0.0255). All-cause mortality at 24 months was 17% and 21% in the FMT and SOCp groups, respectively (p = 0.81). Conclusion Patients who received FMT in addition to SOCp had a significantly lower rate of recurrence and a significantly longer time to subsequent recurrence compared with the SOCp group. There was no significant difference in all-cause mortality between the groups. Disclosures All Authors: No reported disclosures.

Efficacy and Safety of Fecal Microbiota Transplantation in Treatment of Clostridioides difficile Infection among Pediatric Patients: A Systematic Review and Meta-Analysis.

Cases of Clostridioides difficile infection have been rising among the pediatric and adolescent population. Fecal microbiota transplantation (FMT) has emerged as an alternative therapy for recurrent C. difficile infection. We aim to perform the first systematic review and meta-analysis investigating the safety and efficacy of fecal microbiota transplantation for C. difficile infection in children and adolescents. A literature search was performed using variations of the keywords "pediatrics", "C. difficile infection", and "fecal microbiota transplantation" in PubMed, EMBASE, CINAHL, Cochrane, and Google Scholar from inception to 30 June 2022. The resulting 575 articles were independently screened by three authors. Fourteen studies that satisfied the eligibility criteria were included in the meta-analysis. The pooled success rate of FMT in the overall cohort was 86% (95% confidence interval: 77-95%; p &lt; 0.001; I2 = 70%). There were 38 serious adverse events in 36 patients with a pooled rate of 2.0% (95% confidence interval: 0.0-3.0%; p = 0.1; I2 = 0.0%) and 47 adverse events in 45 patients with a pooled rate of 15% (95% confidence interval: 5.0-25.0%; p = 0.02; I2 = 54.0%). There was no death associated with FMT. FMT was concluded to be an effective and safe therapy in pediatric and adolescent patients with C. difficile infection. Underlying comorbidities may impede the efficacy. A rigorous screening process of the donors is recommended prior to embarking on FMT. There is no universal and cost-effective way to monitor the long-term outcomes of FMT. While promising, metagenomic sequencing may not be available in settings with limited resources. Robust data from randomized clinical trials is warranted.

Moxibustion improved the effect of fecal microbiota transplantation donor to dextran sulfate sodium-induced colitis in mice.

Fecal microbiota transplantation (FMT) is beneficial for several gastrointestinal diseases because it alters the intestinal microbiota of recipients. The efficacy of FMT is related to the microbial structure and composition of the donor. Mild moxibustion is a non-invasive and safe traditional Chinese therapy that can regulate the gut microbiota. In this study, we investigated whether moxibustion improved the efficacy of FMT in donors using a dextran sulfate sodium (DSS)-induced colitis mouse model. Normal mice were treated with mild moxibustion at acupoints ST25 and ST36 for 7 days. DSS (2%) was administered for 7 days to induce colitis. FMT was performed on Day 8 and lasted for 7 days. The effect of FMT on mice with DSS was observed on Day 21. Using hematoxylin and eosin staining and immunofluorescence, we analyzed the pathology and cell proliferation after FMT in DSS mice. In addition, using 16 S rDNA sequencing analysis, we investigated the gut microbiota of mice. The results indicated that moxibustion altered the colonic microbial community and increased the relative abundance of specific bacteria without changes in morphology and physiological function in normal mice. FMT using donors with moxibustion reduced body weight loss, inflammation, abnormal microbial community structure, and the relative abundance of some bacteria. These results provide potential strategies for the safe and targeted improvement of FMT donors.

Fecal microbiota transplantation in non-communicable diseases: Recent advances and protocols.

Fecal microbiota transplant (FMT) is a therapeutic method that aims to restore normal gut microbial composition in recipients. Currently, FMT is approved in the USA to treat recurrent and refractory Clostridioides difficile infection and has been shown to have great efficacy. As such, significant research has been directed toward understanding the potential role of FMT in other conditions associated with gut microbiota dysbiosis such as obesity, type 2 diabetes mellitus, metabolic syndrome, neuropsychiatric disorders, inflammatory bowel disease, irritable bowel syndrome, decompensated cirrhosis, cancers and graft-versus-host disease. This review examines current updates and efficacy of FMT in treating conditions other than Clostridioides difficile infection. Further, protocols for administration of FMT are also discussed including storage of fecal samples in stool banks, inclusion/exclusion criteria for donors, fecal sample preparation and methods of treatment administration. Overall, understanding the mechanisms by which FMT can manipulate gut microbiota to provide therapeutic benefit as well as identifying potential adverse effects is an important step in clarifying its long-term safety and efficacy in treating multiple conditions in the future.

S112 Optimal Timing and Donor-Patient Matching of Fecal Microbiota Transplantation for Ulcerative Colitis

Background: In recent years, rectifying imbalances of the gut microbiota with fecal microbiota transplantation (FMT) from healthy donors to patients suffering Ulcerative colitis (UC) have gained clinical interest. As several ongoing trials are exploring the possibility of using FMT to treat UC, discerning factors associated the long-term efficacy of FMT treatment becomes important. Our present study explored the factors related to the efficacy of FMT combined with triple-antibiotic therapy [amoxicillin, fosfomycin, and metronidazole (AFM); (A-FMT)] in patients with UC. Methods: Patients aged 16 years or older suffering from active UC with a Lichtiger’s clinical activity index (CAI) score ≥4 or Mayo endoscopic score (MES) ≥1 participated in the clinical study between March 2014 and October 2019. After rigorous screening, we selected relatives aged 20 years or older, or other volunteer donors. After 2 weeks of oral administration of 3 antibacterial agents, about 200ml of fresh or frozen stool solution of donor stool dissolved in saline solution was obtained by colonoscopy. CAI score at 4 weeks after treatment was defined as "response" if the CAI was ≤9 points and improved by ≥3 points, "remission" if the CAI further improved to ≤3 points, and "relapse" if the CAI increased or treatment was intensified at 48 weeks after treatment in the effective group. Results: Ninety-seven patients (68 males, 29 females, age 39.2 ± 12.9 years, disease duration 8.5 ± 8.0 years, CAI 10.7 ± 3.0, Mayo endoscopic subscore (MES) 1.8 ± 0.7) and 62 donors were included. 93 patients completed A-FMT, with an efficacy rate of 63.9% (ITT) at 4 weeks of treatment and a remission induction rate of 36.1%. The short-term efficacy was associated with pre-treatment Mayo endoscopic score (response P = 0.001, remission P < 0.001), history of corticosteroid treatment (response P = 0.04, remission P = 0.01), and history of tacrolimus treatment (response P = 0.04, remission P = 0.14). The cumulative non-relapse rate was significantly higher in the sibling donor group than in the parent-child donor group (P = 0.001). The age difference between patients and donors also affected the cumulative non-relapse rate (P = 0.01). Conclusion: In our study, the optimal timing for patients to receive A-FMT is before corticosteroid and tacrolimus treatments, and early-stage patients receive fecal transplants from siblings with the best clinical outcomes. While the short-term efficacy of A-FMT was related to the patient's own characteristics, the long-term efficacy was related to patient-donor matching.

Fecal Microbiota Transplantation in Liver Diseases and Recent Developments

Introduction: The intestine, as an important part of the human gastrointestinal tract, provides a favorable milieu for the growth and development of a diverse and large population (approximately 1000 species) of bacteria. Currently, the presence of a cohesive relationship between intestinal bacteria and the host is being well studied and identified. According to the available scientific evidence, the establishment of conditions of imbalance (dysbiosis) in the number and diversity of intestinal microbiome causes the onset/progression of acute and chronic liver disorders (fatty liver, cirrhosis, and liver autoimmune disease). Therefore, modifying the balance and creating conditions of microbial eubiosis by fecal microbiota transplantation can be considered as a novel and host-compatible biological approach in the supportive treatment of liver diseases. Consequently, in the present study, while referring to investigations related to the focus of intestinal microbiome and their relation to liver diseases, the existing scientific evidence on the clinical efficacy of fecal microbiota transplantation in the treatment of some liver diseases and recent advances are discussed.&#x0D; Conclusion: Both basic science research and clinical studies have proven that the fecal microbiota transplantation method can effectively strengthen and improve the gut microbiota during acute and chronic liver diseases, rebuild and restore the balance of the gut microbiome, and accelerate the patient's recovery.&#x0D;

New Baitouweng decoction combined with fecal microbiota transplantation alleviates DSS-induced colitis in rats by regulating gut microbiota metabolic homeostasis and the STAT3/NF-κB signaling pathway

Aim of the studyWe aimed to elucidate the synergistic effect and potential mechanism of New Baitouweng Decoction (NBD) combined with fecal microbiota transplantation (FMT) in rats with DSS-induced ulcerative colitis (UC).Materials and methodsColitis was induced by 5% (w/v) dextran sulfate sodium (DSS) in drinking water for 7 days. NBD or NBD combined with FMT were administered to the colitis rats. Body weight and disease activity index were measured, and the colon histological change was imaged to further examine the efficacy of NBD and FMT. The specific effects of NBD on STAT3/NF-κB signaling pathway and gut microbiota in rats with UC were also investigated.ResultsThe efficacy of NBD in combination with FMT was demonstrated by the lower disease activity index scores; increased tight junction proteins expression; and a lower expression of macrophage marker (F4/80) in colon tissues. NBD combined with FMT elevated the concentrations of short-chain fatty acids and inhibited activation of the JAK2/STAT3/NF-κB related proteins. Furthermore, 16SrDNA sequencing indicated that the gut microbiota in rats with UC was perturbed, in contrast to that in healthy rats. After treatment with NBD and FMT, the diversity and abundance of intestinal flora showed clear improvements. Spearman correlation analysis indicated a strong correlation between specific microbiota and fecal concentrations of acetate, propionate and butyrate.ConclusionsThe protective mechanism of NBD combined with FMT may be linked to regulation NF-κB/STAT3 and restoration of the intestinal flora.

Fecal Microbiota Transplantation Could Improve Chronic Diarrhea in Cynomolgus Monkey by Alleviating Inflammation and Modulating Gut Microbiota.

Chronic diarrhea is associated with enteric dysbiosis and provokes the overuse of antibiotics. Fecal microbiota transplantation (FMT) is a promising therapy, but it shows discrepant clinical efficacy. Bacterial colonization in recipients has been studied, although little is known about the role of gut fungi and Archaea after FMT. In this study, we evaluated the efficacy of human-derived FMT on spontaneous chronic diarrhea cynomolgus monkeys and revealed the effector mechanisms. We demonstrated that FMT can mitigate the appearance of diarrheal symptoms and inhibit the increase in interleukin-6, interleukin-8, interleukin-1β, and interferon-γ and the decrease in interleukin-10 in serum. We confirmed that FMT restored the disturbance of gut bacteria by reducing the relative abundances of potential pathogens, including Cloacibacillus porcorum, Desulfovibrio desulfuricans, Erysipelotrichaceae bacterium 5_2_54FAA, and Erysipelotrichaceae bacterium 21_3, and increasing the levels of Lactobacillus fermentum and Lactobacillus ruminis CAG_367 in diarrheal monkeys. The metabolic pathways of healthy and FMT monkeys' gut bacteria were enriched in amino acid metabolism, carbohydrate metabolism, and lipid metabolism, while the metabolic pathways of pre-FMT monkeys' gut bacteria were enriched in antibiotic production. Moreover, a higher Ascomycota/Basidiomycota ratio, higher Aspergillus levels, and lower Trichosporon asahii abundance were present in intestinal fungi after FMT. Although the abundance of the Archaea Methanosphaera stastmanae did not change significantly, it was inversely correlated with the anti-inflammatory factor IL-4 after FMT. These results support the further development and application of FMT for chronic diarrhea.

Systematic Review: Efficacy and Safety of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection in Children

Background: Recurrent Clostridium difficile infection (RCDI) continues to increase in incidence and severity around the world. Fecal microbiota transplantation (FMT) is commonly used to treat RCDI in adults, but its efficacy and safety in the pediatric population are infrequently studied. Here, we performed a systematic review to evaluate the efficacy and safety of FMT for RCDI in children.Methods: Systematic literature search was performed using PubMed, Science Direct, Nature, Cochrane Library, and Springer to identify original studies in English language published from 2010-2020. The clinical resolution, bacterial resolution, and failure of therapy were calculated as indicators of efficacy of FMT. Adverse events were also calculated as indicators of FMT safety.Results: A total of 21 studies, with 498 pediatric patients were included in this review. There were 418/498 (84%) patients reported clinical and bacterial resolution. There were 67/498 (13%) patients who experienced FMT-related adverse events, with 97% of them had mild adverse event. There was one patient who reported FMT-related serious adverse events which were aspiration pneumonia and dehydration.Conclusion: We found evidence that supports the efficacy and safety of the use of FMT for treatment of recurrent C. difficile infection in children.

Research trends on clinical fecal microbiota transplantation: A biliometric analysis from 2001 to 2021.

Numerous studies on fecal microbiota transplantation (FMT) have been conducted in the past two decades. We aimed to assess the research trends and hotspots in the field of FMT through a quantitative method. The clinical studies of FMT published from 2001 to 2021 were extracted from the Web of Science database. We analyzed the countries, institutions, authors, and keywords of these articles and visually illustrated using VOSviewer and CiteSpace software. The current application of FMT in clinical practice, including indications, efficacy, adverse events, as well as its methodology, such as donor, delivery route, were also evaluated. A total of 227 records were finally identified. The number and rate of annual publications increased gradually. The USA ranked highest in the number of publications. Harvard University was the most influential institution, and Digestive Diseases and Sciences was the most productive journal. Kassam Zain published the most papers, and the high-frequency keywords were mainly related to diseases and techniques. Healthy donors were the most widely used donors, and frozen stool had the highest frequency of use. The predominant delivery route was endoscopy followed by oral capsules and enema. FMT was most frequently performed for the treatment of recurrent Clostridium Difficile Infection. The overall efficacy of FMT was 76.88%, and the incidence of minor and severe adverse events were 11.63% and 1.59%, respectively. This study delineated a comprehensive landscape of the advancement in FMT field. Although in its infancy, FMT is a burgeoning option for the treatment of a variety of diseases associated with gut dysbiosis. To improve the efficacy and reduce adverse events, future studies are warranted to optimize the methodology of FMT.

Challenges and costs of donor screening for fecal microbiota transplantations.

The increasing interest to perform and investigate the efficacy of fecal microbiota transplantation (FMT) has generated an urge for feasible donor screening. We report our experience with stool donor recruitment, screening, follow-up, and associated costs in the context of clinical FMT trials. Potential stool donors, aged between 18-65 years, underwent a stepwise screening process starting with an extensive questionnaire followed by feces and blood investigations. When eligible, donors were rescreened for MDROs and SARS-CoV-2 every 60-days, and full rescreening every 4-6 months. The costs to find and retain a stool donor were calculated. From January 2018 to August 2021, 393 potential donors underwent prescreening, of which 202 (51.4%) did not proceed primarily due to loss to follow-up, medication use, or logistic reasons (e.g. COVID-19 measures). 191 potential donors filled in the questionnaire, of which 43 (22.5%) were excluded. The remaining 148 candidates underwent parasitology screening: 91 (61.5%) were excluded, mostly due to Dientamoeba fragilis and/or high amounts of Blastocystis spp. After additional feces investigations 18/57 (31.6%) potential donors were excluded (mainly for presence of Helicobacter Pylori and ESBL-producing organisms). One donor failed serum testing. Overall, 38 out of 393 (10%) potential donors were enrolled. The median participation time of active stool donors was 13 months. To recruit 38 stool donors, €64.112 was spent. Recruitment of stool donors for FMT is challenging. In our Dutch cohort, failed eligibility of potential donors was often caused by the presence of the protozoa Dientamoeba fragilis and Blastocystis spp.. The exclusion of potential donors that carry these protozoa, especially Blastocystis spp., is questionable and deserves reconsideration. High-quality donor screening is associated with substantial costs.

The Efficacy of Faecal Microbiota Transplant and Rectal Bacteriotherapy in Patients with Recurrent Clostridioides difficile Infection: A Retrospective Cohort Study.

The most effective treatment for recurrent Clostridioides difficile infection (CDI) is faecal microbiota transplantation (FMT); however, the optimal route of administration is thus far unknown. This retrospective cohort study of 343 patients sought to evaluate the efficacy of treatment with FMT capsules, FMT enema, and rectal bacteriotherapy (RBT) during a five-year period. The primary endpoint was clinical resolution from CDI after eight weeks, and secondary endpoints were time to recurrence and death during the follow-up period. The proportion of patients with clinical resolution was 79.9% in the FMT capsule group, 53.3% in the FMT enema group, and 61.8% in the RBT group, corresponding to an adjusted odds ratio of 3.79 (CI: 1.82 to 8.26) in the FMT capsule group compared with FMT enema, and 2.92 (CI: 1.49 to 6.03) compared with RBT. The hazards ratio for recurrence within the first 12 months of follow-up was 0.24 (CI: 0.06 to 0.89) in the FMT capsule group compared with FMT enema, and 0.26 (CI: 0.08 to 0.91) compared with RBT. There was no difference in mortality. In conclusion, FMT capsules were more effective than both FMT enema and RBT as treatment of recurrent CDI and reduced the risk of further recurrences.

Pre-Antibiotic Treatment Followed by Prolonged Repeated Faecal Microbiota Transplantation Improves Symptoms and Quality of Life in Patients with Irritable Bowel Syndrome: An Observational Australian Clinical Experience.

Background The use of faecal microbiota transplantation (FMT) in irritable bowel syndrome (IBS) has frequently failed to induce long-term symptomatic improvement. The use of multiple FMT infusions is one proposed mechanism through which the efficacy of FMT can be amplified. Aims To evaluate the safety and efficacy of a novel six-month FMT treatment protocol in IBS. Methods Patients diagnosed with IBS confirmed by Rome IV Criteria were recruited for single-centre, single-arm, prospective clinical observational study. Participants received one colonoscopically delivered FMT followed by 36 rectal enemas across a six-month period. Validated abdominal symptoms and Short-Form (SF-36) Quality of Life (QOL) questionnaires were collected at baseline, week-12, week-24, and week-56, respectively. Wilcoxon matched-pairs signed-rank tests were conducted to compare differences in abdominal symptom and SF-36 QOL scores over the follow-up timepoints. Statistical significance was set at 5%. Results Sixty participants diagnosed with IBS [IBS-constipation (n = 27), IBS-diarrhoea (n = 18), and IBS-mixed (n = 15)] received the six-month FMT treatment. IBS symptom severity reduction was achieved in up to 61% of respondents at week-12, 64% of respondents at week-24, and maintained in up to 75% of respondents at week-52. Long-term reduction in symptom severity was associated with an increase in QOL, achieved in up to 64% of respondents at week-52 when compared to baseline. Adverse events were experienced in 28% of participants, though they were both transient and mild in nature. Conclusions Six-month sustained FMT appears to be both safe and effective in the short- and long-term alleviation of IBS associated symptoms as well as improving participant QOL.

Long-term safety and efficacy of fecal microbiota transplantation in 74 children: A single-center retrospective study.

BackgroundFecal microbiota transplantation (FMT) is an effective treatment for intestinal and extra-intestinal disorders. Nonetheless, long-term safety and efficacy remain major challenges for FMT applications. To date, few long-term follow-up studies have been published on FMT in children.MethodsRetrospective reviewed the medical charts of 74 patients who underwent 508 FMT courses between August 2014 and July 2019 at our medical center. All the FMT procedures followed uniform standards. Baseline characteristics pre-FMT and follow-up data were collected at 1, 3, 6, 12, 36, 60, and 84 months after FMT. All potential influencing factors for adverse events (AEs) were analyzed and assessed using regression analyses.ResultsA total of 70 (13.7%) short-term AEs occurred in twenty-six patients (35.1%). Most AEs (88.5%) occurred within 2 days post-FMT. A total of 91.4% of the AEs were self-limiting. Ulcerative colitis (UC) and within four times of FMT were associated with a higher rate of AEs (p = 0.028 and p = 0.021, respectively). The primary clinical remission rate after FMT was as high as 72.9%. Twenty-five children were followed for more than 5 years after FMT. The clinical remission rates gradually decreased over time after FMT. During follow-up, none of the patients developed autoimmune, metabolic, or rheumatologic disorders or tumor-related diseases. However, nine children developed rhinitis, five developed rhinitis, were underweight, and six developed constipation.ConclusionsFMT is a safe and effective treatment for dysbiosis in children. The long-term efficacy of FMT for each disease decreased over time. Moreover, multiple FMTs are recommended 3 months post-FMT for recurrent diseases.

S843 Efficacy and Safety of Fecal Microbiota Transplantation in the Treatment of Active Inflammatory Bowel Disease - An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

Introduction: In active inflammatory bowel disease (IBD) patients refractory to standard medical therapy, fecal microbiota transplantation (FMT) has shown to be efficacious. The current literature presents compelling evidence for its use. Herein we performed an updated systematic review and meta-analysis to provide a more robust understanding of the effectiveness and safety of FMT on active IBD patients versus placebo. Methods: We performed a comprehensive literature search on multiple databases in May 2022. Only randomized controlled trials (RCTs) concerning active IBD patients treated with FMT versus placebo were included. Analysis was done using CMA software to compute Odds Ratio, 95% confidence interval. I2 was used to define heterogeneity. (Figure) Results: Ten RCTs with the desired study outcomes were included. We had a total of 437 patients in our study in which each patient met a baseline severity of their ulcerative colitis (UC) or Crohn’s Disease (CD) based on Mayo Score and Harvey Bradshaw Index respectively. Moreover improvement was standardized by the same scales. Our results are consistent with previous meta-analyses demonstrating reassuring efficacy of FMT in IBD patients when compared to placebo. Clinical (OR 1.506, (95% CI 1.259-1.803), P < 0.0001), endoscopic (OR 2.335, (95% CI 1.577-3.457), P < 0.0001), and histologic (OR 3.764, (95% CI 1.986-7.136), P < 0.001) remission were consistent with the aforementioned. Adverse events (OR 0.745, (95% CI 0.537-1.033), P = 0.077) in FMT patients were also as expected. (Table) Conclusion: FMT continues to demonstrates superior efficacy when compared to placebo in terms of active IBD treatment. Likewise, its adverse events compared to placebo display no statistical significance; equating to an analogous safety profile. Larger RCTs with longer follow up and more CD patients are necessary to strengthen the validity of FMT as an IBD therapeutic modality.Figure 1.: The clinical remission among active IBD patients treated with FMT versus placebo. Table 1. - Various outcomes of meta-analysis Outcomes Number of Studies OR & 95% CI P Value (I2) Clinical Remission 10 1.506 & 1.259-1.803 P < 0.001 Endoscopic Remission 6 2.335 & 1.577-3.457 P < 0.001 Histologic Remission 5 3.764 & 1.986-7.136 P < 0.001 Adverse Events 9 0.745 & 0.537-1.033 P = 0.077

S726 Fecal Transplantation Improved Patients’ Reported Outcome After Immune Checkpoint Inhibitor Colitis

Introduction: Immune checkpoint inhibitors (ICIs) have become standard treatment for cancers poorly responsive to traditional chemotherapy. The most common GI toxicity of this class of drugs is ICIs colitis (IMC) associated with difficulty to treat chronic diarrhea and risk of fatality. We have previously demonstrated that fecal microbiota transplantation (FMT) was effective in the treatment of a small number of refractory cases suggesting the gut microbiome is involved in the pathogenesis of ICIs colitis. Further large studies are needed to determine its efficacy. Methods: The present study summarizes our experience with FMT treatment of 37 patients with refractory ICIs colitis. We measured the efficacy of FMT and patients’ reported outcome (PRO) via established MD Anderson Symptom Inventory (MDASI). Among them, 9 patients had concurrent CDI as well at the time of diagnosis. (Table) Results: Thirty-seven patients included in our study, with a median age of 59 years and mostly had genitourinary cancers (35.1%) followed by melanoma (27.0%). Most patients had a peak CTCAE diarrhea grade ≥ 3 (91.9%) and colitis grade ≥ 2 (89.1%). Ulcerous (18, 48.6%) and non-ulcerous (12, 32.4%) inflammation was predominant endoscopic findings. 36 (97.3%) patients received corticosteroids, and 33 (89.1%) received add-on infliximab or vedolizumab. IMC symptom response was 83.7% after FMT with median time to response of 5 days. The rate of complications is 16.2% at 7 days and 5.4% at 30 days, and mostly were transient and mild. Response rate among 28 patients without concurrent CDI was 85.7%. Thirty-five (94.6%) patients demonstrated colitis remission at the last follow up. On the PRO analysis, we observed a favorable trend of significant patient-reported symptom reduction on diarrhea during 12 weeks after FMT, along with improved daily physical functioning on working. (Figure) Conclusion: Evidence is accumulating to suggest that efficacy and prevention of ICI related toxicities is dependent upon a healthy diverse microbiome. In the present study, we have shown that FMT achieved 83.7% success rate in patients with IMC with a favorable safety profile. FMT could become a preferred treatment option for the IMC in the future practice.Figure 1.: Patients Reported Outcome Summary Table 1. - Characteristic before FMT No. (%) (n=37) Concurrent CDI# 9 (24.3%) Highest grade of diarrhea of initial IMC onset – no. (%) 1 or 2 3 (8.1%) 3 or 4 34 (91.9%) Highest grade of colitis of initial IMC onset – no. (%) 1 4 (10.8%) 2- 4 33 (89.2%) Initial endoscopic findings – no (%), n=36 Ulcers 18 (48.6%) Non-ulcer inflammation 12 (32.4%) Normal 6 (16.2%) Hospitalizations – no. (%) 29 (78.3%) Median duration of hospitalization – days (IQR) 8 (5-13) Treatment of GI adverse events – no. (%) Steroid 36 (97.3%) Infliximab/vedolizumab added 33 (89.1%) FMT characteristic and outcome Symptom improvement after FMT, all patients – no (%) 31 (83.7%) Symptom improvement after FMT (no concurrent CDI, n=28) – no (%) 24 (85.7%) Median time from FMT to symptom improvement– days (IQR), n=37 5 (2-10) FMT-related complications within 7 days –no (%) 6 (16.2%) FMT-related complications within 30 days –no (%) 2 (5.4%) Colitis status at the end of the study period Clinical remission – no (%) 35 (94.6%) Persistent symptoms – no (%) 2 (5.4%)