Fecal microbiota transplantation: current challenges and future landscapes

Clinical Microbiology Reviews, Journal Year: 2024, Volume and Issue: 37(2)

Published: May 8, 2024

SUMMARYGiven the importance of gut microbial homeostasis in maintaining health, there has been considerable interest developing innovative therapeutic strategies for restoring microbiota. One such approach, fecal microbiota transplantation (FMT), is main "whole microbiome replacement" strategy and integrated into clinical practice guidelines treating recurrent

Language: Английский

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Rigorous Donor Selection for Fecal Microbiota Transplantation in Active Ulcerative Colitis: Key Lessons From a Randomized Controlled Trial Halted for Futility

Clinical Gastroenterology and Hepatology, Journal Year: 2024, Volume and Issue: unknown

Published: May 1, 2024

Rigorous donor preselection on microbiota level, strict anaerobic processing, and repeated fecal transplantation (FMT) administration were hypothesized to improve FMT induction of remission in ulcerative colitis (UC). The RESTORE-UC trial was a multi-centric, double-blind, sham-controlled, randomized trial. Patients with moderate severe UC (defined by total Mayo 4-10) randomly allocated receive 4 anaerobic-prepared allogenic or autologous FMTs. Allogenic material selected after rigorous screening based microbial cell count, enterotype, the abundance specific genera. primary endpoint steroid-free clinical (total ≤2, no sub-score >1) at week 8. A pre-planned futility analysis performed 66% (n = 72) intended inclusions 108). Quantitative microbiome profiling 44) weeks 0 In total, 72 patients included, which 66 received least 1 (allogenic FMT, n 30 36). At 8, respectively, 3 5 reached (P .72), indicating treatment difference 5% favor FMT. Hence, study stopped due futility. Microbiome showed numerically more enterotype transitions upon compared observed when treated different than their own baseline .01). Primary response associated lower scores, bacterial counts, higher Bacteroides 2 prevalence baseline. did not meet its increased Further research should additionally consider patient selection, sterilized sham-control, frequency, density, viability prior administration. gov, Number: NCT03110289.

Language: Английский

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Overcoming donor variability and risks associated with fecal microbiota transplants through bacteriophage-mediated treatments

Microbiome, Journal Year: 2024, Volume and Issue: 12(1)

Published: July 1, 2024

Abstract Background Fecal microbiota transplantation (FMT) and fecal virome (FVT, sterile filtrated donor feces) have been effective in treating recurrent Clostridioides difficile infections, possibly through bacteriophage-mediated modulation of the gut microbiome. However, challenges like variability, costly screening, coupled with concerns over pathogen transfer (incl. eukaryotic viruses) FMT or FVT hinder their wider clinical application less acute diseases. Methods To overcome these challenges, we developed methods to broaden FVT’s while maintaining efficacy increasing safety. Specifically, employed following approaches: (1) chemostat-fermentation reproduce bacteriophage component remove viruses (FVT-ChP), (2) solvent-detergent treatment inactivate enveloped (FVT-SDT), (3) pyronin-Y inhibit RNA virus replication (FVT-PyT). We assessed processed FVTs a C. infection mouse model compared them untreated (FVT-UnT), FMT, saline. Results FVT-SDT, FVT-UnT, FVT-ChP reduced incidence mice reaching humane endpoint (0/8, 2/7, 3/8, respectively) FVT-PyT, saline (5/8, 7/8, 5/7, significantly load colonizing cells associated toxin A/B levels. There was potential elimination colonization, seven out eight treated FVT-SDT testing negative qPCR. In contrast, all other treatments exhibited continued presence . Moreover, results were supported by changes microbiome profiles, cecal cytokine levels, histopathological findings. Assessment viral engraftment FMT/FVT host-phage correlations analysis suggested that phages likely an important contributing factor efficacy. Conclusions This proof-of-concept study shows specific modifications hold promise addressing related variability risks. Two strategies lead limiting colonization mice, solvent/detergent chemostat propagation emerging as promising approaches.

Language: Английский

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Clinical Guidelines for Fecal Microbiota Transplantation in Companion Animals

Advances in Small Animal Care, Journal Year: 2024, Volume and Issue: 5(1), P. 79 - 107

Published: Aug. 17, 2024

Language: Английский

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Current perspectives on fecal microbiota transplantation in inflammatory bowel disease

Indian Journal of Gastroenterology, Journal Year: 2024, Volume and Issue: 43(1), P. 129 - 144

Published: Feb. 1, 2024

Language: Английский

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In vitro validation concept for lyophilized fecal microbiota products with a focus on bacterial viability

World Journal of Microbiology and Biotechnology, Journal Year: 2025, Volume and Issue: 41(3)

Published: Feb. 27, 2025

Abstract Fecal microbiota transplantation (FMT) effectively treats recurrent Clostridioides difficile infection (rCDI), typically administered as a fresh or frozen stool suspension through colonoscopy, nasojejunal tube, oral capsules. Lyophilized fecal (LFM) are an alternative to FM products. We aimed assess whether lyophilization affects bacterial viability and metabolite levels develop LFM capsules for clinical use in Germany. donations from pre-screened volunteers were aliquoted analyzed microbial cell counting, culture, 16S rRNA gene amplicon sequencing, bile acid assays. Results showed higher counts of viable cells cultured anaerobes unprocessed compared freshly processed ( p = 0.012 < 0.001, respectively). No significant difference was found between (day 0), lyophilized 3) 0.15), nor (days 30 90) 30) 0.07). did not significantly impact profiling. Encapsulation powder required fewer (10–14) than (30). products practical, products, potentially improving storage patient acceptance.

Language: Английский

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Microbiota transplant therapy in inflammatory bowel disease: advances and mechanistic insights

Gut Microbes, Journal Year: 2025, Volume and Issue: 17(1)

Published: March 10, 2025

Microbiota transplant therapy is an emerging for inflammatory bowel disease, but factors influencing its efficacy and mechanism remain poorly understood. In this narrative review, we outline key elements affecting therapeutic outcomes, including donor (such as age patient relationship), recipient factors, control selection, impacting engraftment correlation with clinical response. We also examine potential mechanisms through disease trials, focusing on the interplay between microbiota, host, immune system. Finally, briefly explore future directions microbiota promising treatments.

Language: Английский

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Faecal microbiota transplantation in Crohn’s disease: an Australian randomised placebo-controlled trial protocol

BMJ Open, Journal Year: 2025, Volume and Issue: 15(4), P. e094714 - e094714

Published: April 1, 2025

Introduction The enteric microbiota drives inflammation in Crohn’s disease. Yet, there are no placebo controlled trials evaluating the efficacy and safety of faecal transplantation (FMT) inducing maintaining remission patients with active Microbial Restoration (MIRO) study aims to establish this evidence. Methods analysis At two specialist inflammatory bowel disease centres, 120 enrolled will have a 3-week period diet optimisation (removal ultra-processed foods) together 7-day course antibiotics (to facilitate subsequent FMT engraftment). Patients then be stratified upper gut (for proximal splenic flexure) or lower (distal randomised 2:1 ratio receive anaerobically prepared stool for 8 weeks either by gastroscopy, colonoscopy enemas. Clinical response at (Crohn’s Disease Activity Index (CDAI) reduction ≥100 points <150 points) is primary outcome measure. Non-responders partial responders (CDAI decrease <100 but >70) 8–16. achieving clinical from after 16 1:1 44-week maintenance phase placebo. one donor throughout study. MIRO whether an effective safe therapy induce maintain Ethics dissemination Ethical approval has been received St Vincent’s Hospital Melbourne Human Research Committee (HREC-A 084/21). results disseminated peer-reviewed journals presented international conferences. Trial registration number ClinicalTrials.gov: NCT04970446 ; Registered on 20 July 2021.

Language: Английский

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Impact of Fecal Microbiota Transplant Formulations, Storage Conditions, and Duration on Bacterial Viability, Functionality, and Clinical Outcomes in Patients with Recurrent Clostridioides difficile Infection

Microorganisms, Journal Year: 2025, Volume and Issue: 13(3), P. 587 - 587

Published: March 4, 2025

Fecal microbiota transplantation (FMT) is the most effective therapy for preventing recurrent Clostridioides difficile infection (rCDI). However, impact of FMT formulations and storage conditions on bacterial viability, community structure, functionality, clinical efficacy remains under-investigated. We studied effect different viability (live/dead staining cell sorting), structure (16S rDNA analysis), metabolic functionality (fermentation) frozen lyophilized formulations. The success rates rCDI patients were correlated retrospectively with formulations, durations, host factors using Edmonton program database. Bacterial remained at 10–20% across various was comparable to that fresh FMT. Live dead fractions in both preparations exhibited distinct structures. Storage but not temperatures, negatively affected diversity. More short-chain fatty acids found metabolomic profiling vitro fermentation products than Clinical 537 receiving a single dose significantly among three longer durations advanced recipient age impacted efficacy. Together, our findings suggest should be considered when establishing guidelines product shelf life optimal treatment outcomes.

Language: Английский

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Evaluating Bacterial Viability in Faecal Microbiota Transplantation: A Comparative Analysis of In Vitro Cultivation and Membrane Integrity Methods

Journal of Clinical Laboratory Analysis, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 3, 2024

ABSTRACT Background Faecal microbiota transplantation (FMT) is a developing therapy for disorders related to gut dysbiosis. Despite its growing application, standardised protocols FMT filtrate preparation and quality assessment remain undeveloped. The viability of bacteria in the crucial FMT's efficacy validating protocol execution. We compared two methods—in vitro cultivation membrane integrity assessment—for their accuracy, reproducibility clinical applicability measuring bacterial frozen stool filtrate. Methods Bacterial was evaluated using (i) through fluorescent DNA staining with SYTO9 propidium iodide, followed by flow cytometry (ii) culturable counts (colony‐forming units, CFU) under aerobic or anaerobic conditions. Results Using different types samples (pure culture, germ‐free conventionally bred mice, native heat‐treated human stool), we refined integrated samples. Both integrity‐based cultivation‐based methods exhibited significant variability across filtrates, without correlation. method showed mean coefficient variance 30.3%, ranging from 7.4% 60.1%. Conversely, approach yielded more reproducible results, viable cells 6.4% 0.2% 18.2%. Conclusion offers robust precise data, making it suitable option faecal material evaluation FMT. In contrast, cultivation‐dependent produce inconsistent outcomes.

Language: Английский

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