Efficacy Of Fecal Microbiota Transplantation In Patients Research Articles

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.

Fecal Microbiota Transplantation in Human Immunodeficiency Virus-Infected Patient Population: A Systematic Review and Meta-Analysis.

Patients with human immunodeficiency virus (HIV) infection suffer from alterations in gut microbiota due to recurrent gastrointestinal infections and systemic inflammation. Fecal microbiota transplantation (FMT) appears to be a potential therapy; however, there are concerns about its safety. Likewise, no previous meta-analysis evaluated FMT efficacy in HIV-infected patients. We conducted a thorough electronic search on PubMed, Scopus, OVID, Web of Science, and Cochrane CENTRAL for clinical studies assessing the safety and efficacy of FMT in patients with HIV and gastrointestinal dysbiosis, where FMT was indicated to restore the disrupted microbiota. FMT significantly restored the typical microbiome in patients with Clostridium difficile (C. difficile) and non-C. difficile and reduced the risk of gastrointestinal infections in HIV patients receiving antiretroviral therapy (odds ratio (OR) = 0.774, 95% confidence interval (CI): (0.62, 0.966)). Furthermore, adverse events, such as distention and bloating, associated with FMT were comparable between HIV and health controls (OR = 0.60, 95% CI: (0.07, 4.6)), with no statistical difference. Current evidence demonstrated that FMT is safe and effective in HIV patients suffering from alterations in gut microbiota. We recommend further multi-centric clinical studies to address the optimal transplant amount and source for FMT. To the best of our knowledge, this is the first meta-analysis to assess the safety and efficacy of FMT in patients with HIV.

Safety and efficacy of fecal microbiota transplantation for treatment of systemic lupus erythematosus: An EXPLORER trial

Gut microbiota dysbiosis is involved in the development of systemic lupus erythematosus (SLE). The safety and efficacy of fecal microbiota transplantation (FMT) for the treatment of SLE patients has not been explored. In this 12-week, single-arm pilot clinical trial of oral encapsulated fecal microbiome from healthy donors to patients with active SLE, we aimed to evaluate the safety and efficacy of FMT in patients with SLE (ChiCTR2000036352). 20 SLE patients with SLEDAI ≥6 were recruited. FMT was administered once a week for three consecutive weeks along with standard treatment and the patients were followed for 12 weeks. Safety was evaluated throughout the trial. The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 12. Microbiome composition, levels of short chain fatty acids (SCFAs) in the gut and of cytokines in the sera were measured along with lymphocyte phenotyping. No serious adverse events were observed after FMT. At week 12, the SRI-4 response rate was 42.12%, and significant reductions in the SLEDAI-2K scores and the level of serum anti-dsDNA antibody were observed compared to baseline. Significant enrichment of SCFAs-producing bacterial taxa and reduction of inflammation-related bacterial taxa were observed, along with increased production of SCFAs in the gut and reduced levels of IL-6 and CD4+ memory/naïve ratio in the peripheral blood. Furthermore, SRI-4 responding patients displayed specific microbiota signatures both before and after FMT. The first clinical trial of FMT in active SLE patients provide supportive evidence that FMT might be a feasible, safe, and potentially effective therapy in SLE patients by modifying the gut microbiome and its metabolic profile.

Fecal Microbiota Transplantation for Clostridioides Difficile Infection in Patients with Chronic Liver Disease.

Background Fecal microbiota transplantation (FMT) is a well-established therapeutic option for patients with antibiotic resistant Clostridioides difficile infection (CDI). However, the efficacy of FMT in patients with chronic liver disease remains elusive. Aims We studied the effect of FMT on chronic liver disease (CLD) patients with CDI at our tertiary medical center. Methods A cohort of all patients who received FMT from December 2012 to May 2014 for refractory or recurrent CDI was identified. Patients were monitored for a year after FMT. Descriptive analysis was conducted to compare the effect of FMT in patients with and without CLD. Results A total of 201 patients with CDI received FMT, 14 of which had a history of CLD. Nine of these patients exhibited cirrhosis of the liver with a mean Child-Turcotte-Pugh score of 8. CDI development in these patients was associated with recent exposure to antibiotics and was observed to be significantly different between both groups (17% of CLD patients vs. 58% in the general cohort, p = 0.01). Four patients with CLD received >1 FMT, of which 2 did not respond to treatment. There was no significant difference between patients with liver disease and the rest of the cohort with regard to FMT response (12/14 (87%) vs. 164/187 (88%), p = 0.01). Four patients with CLD received >1 FMT, of which 2 did not respond to treatment. There was no significant difference between patients with liver disease and the rest of the cohort with regard to FMT response (12/14 (87%) vs. 164/187 (88%), Conclusion FMT is a safe and effective therapy against CDI for patients with CLD and cirrhosis.

Efficacy of Fecal Microbiota Transplant in Hematological Cancers Patients with Recurrent Clostridioides Difficile Infection: A Systemic Review and Meta-Analysis

Introduction: Fecal microbiota transplant (FMT) has been shown to be an effective treatment for recurrent Clostridioides difficile infection (CDI). Immunosuppression is one of the risk factors for CDI. However, most of the trials evaluating efficacy of FMT have excluded immunocompromised patients. Patients with hematological cancers represent a major class of immunocompromised patients. Hence, we performed a meta-analysis to evaluate the efficacy of FMT in patients with hematological cancer for the treatment of recurrent CDI. Methods: A systematic search of Medline, Embase, and Web of Science was performed from January 2000 up to December 2018. Articles included for meta-analysis were case series and case reports that assessed efficacy of FMT in hematological cancer patients were included. Study quality was assessed using the Newcastle-Ottawa scale. The main outcomes were pooled proportions of patients achieving cure after first FMT. The cure rate was defined as resolution of diarrhea without any recurrence. Results: 10 studies (5 case series and 5 case reports) were included in the analysis, making up 29 patients who underwent 38 total FMT procedures. The follow up period ranged from 1- 14 months. Of the included patients, 17 had leukemia, 10 had lymphoma and 2 patients had multiple myeloma and myelodysplastic syndrome each. 7 of these patients had undergone hematopoietic stem cell transplant. The pooled cure rate was 82% [confidence interval (CI) 67-94%] after 1 FMT with no heterogeneity (I2=0%). Minor publication bias was seen on visual inspection of funnel plot. FMT was generally well tolerated by these patients. No serious side effects were reported in any study. One of the studies reported death due to cardiac arrest 5 days after FMT which was thought to be unrelated to the procedure. Mild side effects including mild abdominal pain, transient diarrhea, fecal urgency, constipation and nausea were reported in 5 patients. Conclusion: Based on limited observational data, FMT seems to be an effective and safe modality for management of recurrent CDI in patients with hematological cancers. However, further prospective clinical trials are needed to establish its safety as a first line therapy for recurrent CDI in this population. Figure Disclosures Jamshed: Takeda Pharmaceutical: Honoraria. Khanna:Rebiotix, Inc: Research Funding; Probio Tech, LLC: Consultancy; Facile Therapeutics: Consultancy; Shire, Plc: Consultancy.

Combined Endoscopic and Oral Fecal Microbiota Transplantation in Patients with Antibiotic-Dependent Pouchitis: Low Clinical Efficacy due to Low Donor Microbial Engraftment

Background and Objective: A significant number of pouch patients develop antibiotic-dependent pouchitis (ADP). Microbial dysbiosis is thought to be a major driver of clinical symptoms in ADP. The objective of this proof of concept study was to evaluate safety, efficacy, and donor microbial engraftment of an intensified fecal microbiota transplant (FMT) consisting of a single endoscopic FMT followed by daily oral FMT for 2 weeks in patients with ADP. Methods: We performed a prospective placebo-controlled double-blind FMT trial in patents with established ADP and planned to enroll 20 patients in this proof of concept study. In case of non-response, patients were offered an optional open label active FMT treatment. The endpoints were safety, clinical remission without need for antibiotics during 16 weeks of follow-up, quantitative changes of fecal calprotectin (FCP), and engraftment of donor FMT as determined by metagenomic sequencing of the V4 region of the 16S rRNA gene. Results: Due to a lower than expected clinical remission rate and low FMT engraftment, enrollment in the study was stopped prematurely after 6 patients were included. All 6 patients enrolled in the placebo-controlled portion failed to respond and needed antibiotic rescue therapy shortly after FMT. FCP increased in the majority of patients in the setting of relapse after FMT. In the active open label FMT extension study 1 out of 5 patients achieved antibiotic-free clinical remission. FMT engraftment after active FMT was observed only in this single patient, whereas engraftment of donor FMT occurred in none of the other patients receiving active FMT, paralleling the lack of clinical response. Conclusions: Low donor FMT engraftment resulted in low clinical efficacy of FMT in patients with ADP. Before embarking on larger clinical trials with FMT in patients with ADP or other forms of pouchitis, it is mandatory to explore approaches for superior FMT engraftment.

Fecal microbiota transplantation for the treatment of Clostridium difficile infection

Clostridium difficile, a major cause of healthcare-associated diarrhea due to perturbation of the normal gastrointestinal microbiome, is responsible for significant morbidity, mortality, and healthcare expenditures. The incidence and severity of C difficile infection (CDI) is increasing, and recurrent disease is common. Recurrent infection can be difficult to manage with conventional antibiotic therapy. Fecal microbiota transplantation (FMT), which involves instillation of stool from a healthy donor into the gastrointestinal tract of the patient, restores the gut microbiome to a healthy state. FMT has emerged as a promising new treatment for CDI. There are limited data on FMT for treatment of primary CDI, but FMT appears safe and effective for recurrent CDI. The safety and efficacy of FMT in patients with severe primary or severe recurrent CDI has not been established. Patients with inflammatory bowel disease (IBD) who undergo FMT for CDI may be at increased risk of IBD flare, and caution should be exercised with use of FMT in that population. The long-term safety of FMT is unknown; thus, rigorously conducted prospective studies are needed.

Mo1818 Effect of Aging on the Fecal Microbiome in Healthy Donors for Fecal Microbiota Transplant

Background: Fecal microbiota transplant (FMT) is fast emerging as a promising therapy for recurrent clostridium difficile colitis in patients not responding to antibiotic therapy. However all patients for FMT need a fecal sample from a healthy donor. However the effect of age on the fecal microbiome of the healthy donor and its clinical efficacy, has not been examined previously. Aim: To examine fecal samples of healthy human subjects of various ages, volunteering to donate their samples for FMT by genomic analysis and clinical outcom. Methods: All healthy subjects who were rigorously screened for infectious disease and selected as donors for FMT were included in the study. Fecal samples were processed and analyzed using 16S rRNA gene amplicon sequencing. Microbiota compositions were studied using standard 16S rRNA analysis tools (CloVR-16S). Differences in bacterial phylum abundance and diversity (Shannon index) of the donor fecal microbiota were analyzed using three different cutoff for age of 50 years, 60 years and 70 years. Effect of fecal microbiota from donors of different age groups on efficacy of FMT in patients with RCDI was monitored in the GI clinic. Results: Fecal microbiota of 30 healthy donors was analyzed. The mean age of the donors was 50±15.3 years and ranged between 20 years to 82 years. Of these 30 donors, 18 (60%) were males and 26 (87%) were related to the recipients. The Shannon index did demonstrate significant increase in the fecal microbiome diversity in 70+ year old donors, as demonstrated in Figure 1. Althoughmicrobiome dissimilarity between the younger donors groups was relatively larger than the older donors groups on weighted UniFrac metric analysis, the association was not statistically significant. At phylum level, while the relative abundance of Firmicutes was higher in older groups (p<0.05), Actinobacteria was higher in younger groups (p<0.05). At family and genus level, the relative abundance of bifidobactericeae members were higher in younger group of donors than older group (p<0.05). However, despite these genomic differences in the fecal microbiota with ageing, all of our patients recovered completely from the recurrent clostridium difficile infection. Conclusion: This data suggests that there is a trend towards increase in relative abundance of Firmicutes with ageing. Furthermore the younger subjects were more dissimilar by measuring phylogenetic distances than the older donors. These observations indicate that human fecal microbiome evolves with ageing process and associated factors.

Mo1820 Activation of the GCN2/eIF2alpha/ATF4 Signaling Pathway Triggers Autophagy Response to Infection With Crohn's Disease-Associated Adherent-Invasive Escherichia coli

Background: Fecal microbiota transplant (FMT) is fast emerging as a promising therapy for recurrent clostridium difficile colitis in patients not responding to antibiotic therapy. However all patients for FMT need a fecal sample from a healthy donor. However the effect of age on the fecal microbiome of the healthy donor and its clinical efficacy, has not been examined previously. Aim: To examine fecal samples of healthy human subjects of various ages, volunteering to donate their samples for FMT by genomic analysis and clinical outcom. Methods: All healthy subjects who were rigorously screened for infectious disease and selected as donors for FMT were included in the study. Fecal samples were processed and analyzed using 16S rRNA gene amplicon sequencing. Microbiota compositions were studied using standard 16S rRNA analysis tools (CloVR-16S). Differences in bacterial phylum abundance and diversity (Shannon index) of the donor fecal microbiota were analyzed using three different cutoff for age of 50 years, 60 years and 70 years. Effect of fecal microbiota from donors of different age groups on efficacy of FMT in patients with RCDI was monitored in the GI clinic. Results: Fecal microbiota of 30 healthy donors was analyzed. The mean age of the donors was 50±15.3 years and ranged between 20 years to 82 years. Of these 30 donors, 18 (60%) were males and 26 (87%) were related to the recipients. The Shannon index did demonstrate significant increase in the fecal microbiome diversity in 70+ year old donors, as demonstrated in Figure 1. Althoughmicrobiome dissimilarity between the younger donors groups was relatively larger than the older donors groups on weighted UniFrac metric analysis, the association was not statistically significant. At phylum level, while the relative abundance of Firmicutes was higher in older groups (p<0.05), Actinobacteria was higher in younger groups (p<0.05). At family and genus level, the relative abundance of bifidobactericeae members were higher in younger group of donors than older group (p<0.05). However, despite these genomic differences in the fecal microbiota with ageing, all of our patients recovered completely from the recurrent clostridium difficile infection. Conclusion: This data suggests that there is a trend towards increase in relative abundance of Firmicutes with ageing. Furthermore the younger subjects were more dissimilar by measuring phylogenetic distances than the older donors. These observations indicate that human fecal microbiome evolves with ageing process and associated factors.