Disentangling Microbiome Engraftment by Multi-omics of the Gut Ecosystem During Fecal Transplant
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 90
- 试验地点
- 2
- 主要终点
- Longitudinal Analysis of Host-Microbiome Interactions Driving Microbial Engraftment
研究概览
简要总结
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.
详细描述
Gut microbiota regulates key functions in humans, i.e. immunity and metabolism, and is a pathogenic pathway of many disorders, including recurrent C. difficile infection (rCDI), ulcerative colitis (UC), and metabolic syndrome (MetS). Microbiota therapeutics (MT) have raised high expectations without comparable results. Among MT, fecal microbiota transplantation (FMT), the transfer of healthy donor feces to a recipient with a microbiome-associated disease, has achieved high (nearly 90%) cure rates of rCDI but lower and less consistent results in chronic disorders, i.e. UC or MetS. Clinical and microbial features seem to be related with FMT outcomes, but consistent predictors are not available.
Donor-recipient microbiome engraftment may be critical for the clinical success of FMT. In a pooled meta-analysis of 20 FMT studies in different diseases by our group and the Segata Lab , donor recipient microbiome engraftment was associated with clinical response regardless of disease, differed among bacterial taxa, and was predicted by machine learning (ML). Other factors could influence engraftment, but evidence is unclear. Virome and fungome, have been linked to FMT success, but their engraftment kinetics is unknown. Host factors, i.e. genetics, gut immunity and microbial metabolites are supposed to play a role in engraftment, but supporting data are still absent.
Crucial issues of the engraftment dynamics remain still unsolved, including 1) which are the interactions among host factors, microbial strains, and products during FMT; 2)whether and how they influence engraftment and 3) clinical outcomes.Our aim is to disentangle the dynamics of microbiome engraftment and correlate them to clinical outcomes.
OBJECTIVES
Primary objectives - To assess the longitudinal multidomain interactions of host and microbiome variables and their influence on microbial engraftment
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Coorte: Patients affected by Ulcerative Colitis
- •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.
- •Coorte: Patients affected by metabolic syndrome
- •Age ≥18 years.
- •Patients with MetS (high glycaemia levels (> 100 mg/dL), hypertension (> 130/85 mmHg), raised triglyceride levels (> 150 mg/dL), low high-density lipoprotein cholesterol levels (< 40 mg/dL in men; <50 mg/dL in women), and abdominal obesity (waist circumference of > 102 cm in men; >88 cm in women)
- •Stable treatment (> 8 weeks) of one of these disorders, included in MetS definition.
- •Ability to give informed consent
- •Coorte: Patients affected by rCDI
- •Age ≥18 years
- •Mild recurrent Clostridioides difficile infection (26)
- •Ability to give informed consent.
排除标准
- •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
- •Critical and severe comorbidities
- •Inability to give informed consent.
研究组 & 干预措施
Recurrent C. difficile infection (rCDI) Cohort
Patients with recurrent C. difficile infection (rCDI) will be recruited among those referred to the Digestive Disease Centre (CEMAD) of the Fondazione Policlinico Universitario A. Gemelli IRCCS. Patients with all inclusion criteria and none of the exclusion criteria will be considered for this study.
干预措施: Fecal microbiota transplantation (FMT) (Other)
Ulcerative Colitis (UC) Cohort
Patients with Ulcerative Colitis (UC) will be recruited among those referred to the Digestive Disease Centre (CEMAD) of the Fondazione Policlinico Universitario A. Gemelli IRCCS. Patients with all inclusion criteria and none of the exclusion criteria will be considered for this study.
干预措施: Fecal microbiota transplantation (FMT) (Other)
Metabolic syndrome (MetS) Cohort
Patients with metabolic syndrome (MetS), will be recruited among those referred to the Digestive Disease Centre (CEMAD) and to the Endocrine and Metabolic Diseases Unit of the Fondazione Policlinico Universitario A. Gemelli IRCCS.
干预措施: Fecal microbiota transplantation (FMT) (Other)
结局指标
主要结局
Longitudinal Analysis of Host-Microbiome Interactions Driving Microbial Engraftment
时间窗: 60 months
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.
次要结局
- Longitudinal Analysis of Host-Microbiome Interactions and Their Impact on Clinical Outcomes(60 months)
研究者
Gianluca Ianiro
Principal Investigator, MD, PhD
Catholic University of the Sacred Heart