Changes in Recipients Gut Microbiota After Fecal Microbiota Transplantation

Study Overview
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Brief Summary
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Clostridioides diﬃcile infection (CDI) is the most common cause of nosocomial diarrhea, and the most common health care-associated infectious disease in the United States, accounting for 15% of overall infections, nearly 30.000 deaths per year an estimated economic expense of $5 billion/year. In the last decade, most of the burden related to CDI depends on recurrence CDI (rCDI) (3). rCDI is known to extend the hospitalization length, and to be associated with increased morbidity and mortality rates. Furthermore, rCDI is often, more than primary infection, associated with life-threatening complications, including pseudomembranous colitis, toxic megacolon, shock, perforation, bloodstream infection (BSI), sepsis, caused by intestinal bacteria or fungi with a mortality rate nearly 50%, and death. Fecal microbiota transplantation (FMT), defined as the infusion of feces from healthy donors to recipient with disorders associated to dysbiosis, is known to be a highly effective treatment option against CDI. FMT is also more effective than standard treatment with vancomycin and it is recommended by International Guidelines for treating multiple recurrence of CDI. Despite the increasing body of evidence about the clinical efficacy of FMT for the treatment of rCDI, mechanisms for this clinical efficacy are also unknown. Metagenomics analysis is known as a good option to examine gut microbiota and to estimate microbial diversity. The aim of this study is to evaluate changes in microbial composition in rCDI patients after FMT, using metagenomics analysis.

Detailed Description
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Clostridioides diﬃcile infection (CDI) is the most common cause of nosocomial diarrhea, and the most common health care-associated infectious disease in the United States, accounting for 15% of overall infections, nearly 30.000 deaths per year an estimated economic expense of $5 billion/year. In the last decade, most of the burden related to CDI depends on recurrence CDI (rCDI) (3). rCDI is known to extend the hospitalization length, and to be associated with increased morbidity and mortality rates. Furthermore, rCDI is often, more than primary infection, associated with life-threatening complications, including pseudomembranous colitis, toxic megacolon, shock, perforation, bloodstream infection (BSI), sepsis, caused by intestinal bacteria or fungi with a mortality rate nearly 50%, and death. Fecal microbiota transplantation (FMT), defined as the infusion of feces from healthy donors to recipient with disorders associated to dysbiosis, is known to be a highly effective treatment option against CDI. FMT is also more effective than standard treatment with vancomycin and it is recommended by International Guidelines for treating multiple recurrence of CDI. Despite the increasing body of evidence about the clinical efficacy of FMT for the treatment of rCDI, mechanisms for this clinical efficacy are also unknown. Metagenomics analysis is known as a good option to examine gut microbiota and to estimate microbial diversity. The aim of this study is to evaluate changes in microbial composition in rCDI patients after FMT, using metagenomics analysis. The investigators will carry out a single-center observational perspective study. Patients will be recruited among those referred to the gastroenterology unit of the Fondazione Policlinico Universitario A. Gemelli. Patients with all inclusion criteria and none of the exclusion criteria (detailed in the specific section of this website) will be considered for this study. Before FMT procedure, demographic data will be collected by the gastrointestinal disease staff. Moreover, patients will be requested to give stool samples to be collected in a sterile, sealed container and stored at -80°C for metagenomic assessment of gut microbiome and meta-transcriptome assessment by the microbiology staff. Patients, according to clinical practice, will receive FMT procedure by colonoscopy. Each patient of the study will receive faeces from one single donor without any specific recipient-donor match. The selection of stool donors will be performed by the gastroenterology unit staff following protocols previously recommended by international guidelines and according the new recommendation imposed by the reorganisation of faecal microbiota transplant during the COVID-19 pandemic. All faecal infusates will be manufactured in the microbiology unit of our hospital. Only frozen faeces will be used. Preparation of frozen faeces will follow protocols from international guidelines. Follow-up visits will be performed by physicians from the gastroenterology unit. All patients will be followed up for 3 months after the end of treatments. Follow-up visits will be scheduled at week 1, week 2, week 4, and week 12, after the end of treatments. At each visit investigators will collect stool samples for microbiome analysis. Study Outcomes are detailed in the specific section of this website. For microbiome analysis, statistical differences between group means will be calculated using a two-tailed Wilcoxon-Rank Sum Test, through the R statistical software package (R Core Team, Vienna, Austria).

Official Title
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Assessment Of Changes In Gut Microbiota Of Patients With Recurrent Clostridioides Difficile Infection After Fecal Microbiota Transplantation: Prospective Study

Conditions
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Clostridioides Difficile Infection Recurrence

Intervention / Treatment
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* Other: FMT from healthy donors


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recurrent Clostridioides difficile infection Age between 18 and 90 years old Ability to provide written informed consent Ability to be compliant with the scheduled procedures Exclusion Criteria: Another known gastrointestinal infection apart from C. difficile infection . Known active gastrointestinal disorders (e.g. infectious gastroenteritis, coeliac disease, inflammatory bowel disease, irritable bowel syndrome, chronic pancreatitis, biliary salt diarrhoea) Previous colorectal surgery or cutaneous stoma Current or recent (< 6 weeks) therapy with drugs that could possibly alter gut microbiota (e.g. antimicrobials, probiotics) Decompensated heart failure or heart disease with ejection fraction lower than 30% Severe respiratory insufficiency Psychiatric disorders Pregnancy or breastfeeding Unable to give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: FMT from healthy donors|This intervention is represented by the administration, in the recipients' gut, of healthy donor microbiota through FMT|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Qualitative and quantitative characteristics of recipients' microbiome 30 days after FMT. | The investigators will evaluate the characteristics of recipients' microbiome, assessed by metagenomics analysis, 30 days after FMT compared with baseline. | 1 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Qualitative and quantitative characteristics of recipients' microbiome 7,15,90 days after FMT. | The investigators will evaluate the characteristics of recipients' microbiome, assessed by metagenomics analysis, 7,15,90 days after FMT compared with baseline. | 3 months | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | The number of participants with treatment-related adverse events (assessed by CTCAE v4.0) will be recorded throughout the study period. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clostridioides difficile infection, Fecal Microbiota Trasplantation, Engraftment