Establishment of the Human Intestinal and Salivary Microbiota Biobank - Gastrointestinal Diseases
Condition: Clostridium Difficile Infection; Multi Drug Resistant Organisms; Chronic Inflammatory Bowel Disease; Irritable Bowel Syndrome; Hepatic Encephalopathy
MeSH terms: Clostridium Infections; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Hepatic Encephalopathy; Gastrointestinal Diseases; Brain Diseases
Study type: Observational

Summary: 
      This is a prospective, clinical, multicentre study aimed to collect biological samples and
      study microbiota from subjects with Clostridium Difficile (CDI), subjects affected by Multi
      Drug Resistant Organisms (MDRO) infection, subjects with Chronic Inflammatory Bowel Disease
      (IBD), subjects with Irritable Bowel Syndrome (IBS), subjects with Hepatic Encephalopathy and
      from healthy volunteers. Microbiota is a complex consortium of microorganisms, located at the
      mucosal level (in particular intestinal, oral and vaginal) having a key role in human health
      and in the onset of several diseases. Microbiota alterations have been found in several
      diseases (gastrointestinal, metabolic, renal, oncological, gynaecological)

      The study will allow to:

        -  Provide biological samples (faeces, saliva, blood, urine) from healthy volunteers and
           patients to the first Italian microbiota biobank;

        -  Study microorganisms using different in vitro and in vivo techniques;

        -  Study the link between the microbiota and the disease. This study is part of the BIOMIS
           project (Project Code: ARS01_01220), presented as part of the "Avviso per la
           presentazione di progetti di ricerca industriale e sviluppo sperimentale nelle 12 aree
           di specializzazione individuate dal PNR 2015-2020" and admitted to funding under the
           National Operational Program "Ricerca e Innovazione" 2014-2020 by directorial decree of
           MIUR - Department for Higher Education and Research - n. 2298 of 12 September 2018.
           BIOMIS includes several clinical studies that enrol patients with different pathologies
           to collect and store biological samples and study microbiota.
    

Detailed description: 
      The primary aim of this multicentric study is to populate the first national microbioma
      biobank with biological samples (fecal, salivary, urinary and blood samples) subjects
      suffering from selected disease (CDI, MDRO, IBD, IBS and Hepatic Encephalopathy), and healthy
      volunteers.

      The secondary aim is the characterization of microorganisms of the biobank and study of the
      microbiota-pathology relationship using meta-omics, in vitro and in vivo approaches.

      The study plans to enrol 225 subjects at Policlinico of Bari, University of Perugia and
      Policlinico Agostino Gemelli Rome, according to the inclusion/exclusion criteria. The study
      participation is voluntary, and the subjects have the right to withdraw from the study at any
      time and for any reason.

      During the study, 3 visits are planned:

        -  Visit 0 (V0), including description of the objectives and procedures study, signature
           written informed consent, inclusion/exclusion criteria evaluation, medical examination
           (blood pressure measurement, abdominal and thoracic physical examination), filling in of
           the anamnestic questionnaire, delivery of the coproculture kit, delivery of kits for the
           collection of fecal, salivary and urinary material to be reported at Visit 1 and
           delivery of a 3-day food diary, to be completed autonomously in the days preceding the
           Visit 1.

        -  Visit 1 (V1) - at least 4 days after V0, including delivery of the of the collected
           biological material (feces, saliva, urine), and of a 3-day food diary, filling in of the
           new signs and symptoms anamnestic questionnaire and blood sampling by medical staff. For
           MDRO patients rectal swab collection.

        -  Telephone evaluation: administration of a "Food Frequency Questionnaire" to assess the
           subjects' alimentary habits.

      Standard Operative Procedures (SOP) for samples storing, transport and processing will be
      adopted to ensure samples stability and grant results validity and quality.

      Following collections, samples will be processed in different aliquots that will be used for:

        -  routine screening;

        -  storage in the first Italian human microbiote biobank (I.R.C.C.S. - Istituto Tumori
           "Giovanni Paolo II", Bari);

        -  evaluation of the proteomic, metascriptomic, metabolomic, metagenomic, and metagenetic
           profile;

        -  Evaluation of the transcriptomic profile of PBMCs of healthy subjects and subjects
           affected by selected pathologies and evaluation of the serum proteomic profile
           Furthermore, molecular characterization of pathogenic microorganisms and pathogenic
           biotypes (pathovars) of commensal species of subjects with selected pathologies will be
           conducted.

      Part of the biological material will be used for animal studies on the physiopathological
      role of the human intestinal microbiota transplanted into mouse models of pathology and
      Germ-free mouse models (specific animal study protocol developed).

      Also, in vitro studies on mucosal models to evaluate the interaction between the microbiota
      and the intestinal mucosa will be conducted.

      The study foresees no more than minimal risk associated with blood sampling procedures. All
      the necessary measures to avoid any risks / inconveniences resulting from participation of
      the subject under study will be taken.

      The study is compliant with Good Clinical Practice. Study protocol and all related documents
      have been approved by approved by the Independent Ethics Committees (IEC) of the involved
      clinical sites.

      To ensure the protection and confidentiality of the participants' data, all study activities
      will be carried out in accordance with the European General Data Protection Regulation,
      Regulation (EU) 2016/679, which repeals Directive 95/46/EC.
    

Intervention name(s): Biological sample collection; Questionnaire; Medical examination
Intervention type(s): Other; Other; Other
Intervention description(s): Collection of faeces, coproculture examination, urine, saliva, PBMC and blood for biobanking, to evaluate the proteomic, metascriptomic, metabolomic, metagenomic, and metagenetic profile, and to perform routine screening. Analysis for the identification, quantification and characterization of health-promoting bacteria; Anamnestic questionnaire, 3-day food questionnaire, Food Frequency Questionnaire; Blood pressure measurement, abdominal and thoracic physical examination
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Subjects with C. Difficile (CDI), subjects affected by Multi Drug Resistant Organisms
        (MDRO) infection, subjects with Chronic Inflammatory Bowel Disease (IBD), subjects
        suffering from Irritable Bowel Syndrome (IBS) and subjects with Hepatic Encephalopathy
        attending one of the clinical centres involved in the study.

        Healthy volunteers will be recruited by invitation. Enrolled subjects must not have any
        family relationship and hierarchical subordination with the hospitals in which biological
        samples will be collected.
      
Biospecimen description: 
      faeces, saliva, blood, serum, urine, PBMC
    
Keywords: Microbioma biobank; Biological human samples; Gastrointestinal disease; Meta-omics approaches; Microbiota-pathology relationship