Multi-omics Dissection of Gut Microbiome Engraftment During FMT
Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorCatholic University of the Sacred Heart
About this trial
The gut microbiota plays a key role in immunity and metabolism and contributes to diseases such as recurrent C. difficile infection (rCDI), ulcerative colitis (UC), and metabolic syndrome (MetS). Microbiota therapeutics, particularly fecal microbiota transplantation (FMT), show promise-achieving \~90% cure rates in rCDI-but demonstrate variable efficacy in chronic conditions. Microbiome engraftment appears critical for FMT success, yet consistent predictors remain lacking. A meta-analysis of 20 FMT studies by our group and the Segata Lab linked engraftment to clinical response across diseases, with taxon-specific patterns and ML-based predictability. While viral, fungal, host immune, genetic, and metabolic factors may affect engraftment, their roles are not well-defined. Key unresolved questions include the interplay among host factors, microbial strains, and metabolites, their influence on engraftment, and impact on clinical outcomes. This study aims to unravel microbiome engraftment dynamics and link them to therapeutic response.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥18 years.
UC with mild-to-moderate activity (total Mayo score 3-10 + endoscopic subscore≥1) (23)
UC during stable maintenance therapy (> 8 weeks with salicylates, immunosuppressants);
Ability to give informed consent.
Disqualifiers
Pregnancy, breastfeeding, and the refusal to follow an effective contraception method for all the study duration (for women).
Known active gastrointestinal disorders (e.g. infectious gastroenteritis except CDI, coeliac disease, irritable bowel syndrome, chronic pancreatitis, biliary salt diarrhoea) apart from UC, with clinical characteristics reports in inclusion criteria.
Antimicrobial treatment up to 4 weeks prior to screening visit (apart for patients with rCDI)
Previous colorectal surgery or cutaneous stoma
Trial design
Design model
Parallel
Treatments tested in this trial
Fecal microbiota transplantation (FMT)
Other interventionPatients will receive a first donor FMT by colonoscopy, after a pre-conditioning with vancomycin and neomycin + bacitracin for 3 days, because data from our group show that pre-FMT antibiotics are associated with higher rates of microbial engraftment. Then they will receive two cycles, respectively after 3 and 7 days after colonoscopy - FMT, of frozen donor FMT capsules (15 capsules b.i.d. per 3 days). Patients will always receive feces from the same donor.
Treatment groups
90 Participants
are divided into 3 treatment groupsGroup A: Recurrent C. difficile infection (rCDI) CohortExperimental treatment 1 intervention
Group B: Ulcerative Colitis (UC) CohortExperimental treatment 1 intervention
Group C: Metabolic syndrome (MetS) CohortExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Longitudinal Analysis of Host-Microbiome Interactions Driving Microbial Engraftment
To assess the longitudinal multidomain interactions of host and microbiome variables and their influence on microbial engraftment. Microbiome taxonomic profiling will be performed following the general guidelines and relying on the bioBakery computational environment. The taxonomic profiling and quantification of organisms' relative abundances of all metagenomic samples will be quantified using MetaPhlAn 3.0 (species-level profiling) and StrainPhlAn 3 (strain-level profiling). Metatranscriptomics (MTR), metabolomics (MTB) and metaproteomics (MTP) will be performed in stool samples. Through Multiplex Bead analysis for the assessment of specific cytokine in biopsy samples will be perform, following manufacturer's instructions. Flow cytometry will be also performed in colonic biopsies to identify the specific phenotype of immune cells localized in the mucosal samples.
Time frame
60 monthsSecondary outcomes
1
Longitudinal Analysis of Host-Microbiome Interactions and Their Impact on Clinical Outcomes
A longitudinal multidomain analysis will investigate host-microbiome interactions using taxonomic profiling, metatranscriptomics, metabolomics, and metaproteomics in stool samples. Cytokine profiling in biopsy samples will be performed via Multiplex Bead analysis. These variables will be correlated with clinical outcomes, including disease activity in UC patients (Mayo score), insulin sensitivity in MetS patients (Matsuda and OGIS indices post-OGTT), and clinical features such as diarrhea and fecal C. difficile toxin in recurrent CDI cases.
Time frame
60 monthsSponsors and contacts
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Source ClinicalTrials.gov
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