JE/COL-MIME: Jejunal Luminal and Colonic Mucosa-Associated Microbiota in Metabolic Diseases: Methods, Identification and Causalities

Sponsor

Institut National de la Santé Et de la Recherche Médicale, France (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05186389

Collaborator

(none)

Enrollment

13.9

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This clinical study will investigate Jejunal Microbiota in Metabolic Diseases (Je-MiMe, n=45) and Colonic mucosa-associated Microbiota in Metabolic Diseases (Col-MiMe, n=45).

Each cohort (Je and Col -MiMe) is composed of three groups: participants with obesity (n=15) with obesity and with type II diabetes (n=15).

This research protocol is organized in two parts. Each part of this study will recruit 45 participants that are only recruited in one of the parts of the protocol (JE-MIME or COL-MIME). Thus, in total, the study will include 90 patients. Each part of this study is composed of 3 groups: 1) "Control Group ", 2) Obese group (Ob), 3) Obese and Type 2 Diabetes group (ObD). Control groups for part I (JE-MIME) and part 2 (COL-MIME) are composed of different participants. Each group is composed of 15 human adult volunteers for the JE-MIME study (part 1) and 15 participants for the COL-MIME study (part 2). Total number of participants is 45 for part 1, and 45 for part 2. Total number for this project is 90.

Microbiota wil be collected during an endoscopy or coloscopy which is planned as routine care for the patients.

Primary objectives are to characterize jejunal (JE-MIME, Part I of the study) and colonic mucosa-associated microbiota (COLMIME, Part II of the study) and compare both microbiota to faecal microbiota (evaluate differences and similarities between jejunal microbiota or mucus-associated microbiota and faecal microbiota).

Secondary objectives are to 1) Correlate microbiota with metabolic health and inflammatory markers; 2) Correlate microbiota with lifestyle and neuropsychological health.

Both the jejunal microbiota and mucus-associated microbiota are strong integrators of nutritional environment and intestinal health status, respectively, compared to the fecal microbiota. This study will help to better understand the physiopathology of metabolic diseases. This research could lead to finding specific microbiota members, either from the jejunal compartment or from the inner mucus layer, crucial for the promotion / protection of chronic intestinal inflammation and associated metabolic health.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus Obesity Metabolic Disease

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

90 participants

Observational Model:

Cohort

Time Perspective:

Other

Official Title:

Jejunal Luminal and Colonic Mucosa-Associated Microbiota in Metabolic Diseases: Methods, Identification and Causalities

Anticipated Study Start Date :

Jan 26, 2022

Anticipated Primary Completion Date :

Feb 26, 2023

Anticipated Study Completion Date :

Mar 26, 2023

Arms and Interventions

Arm	Intervention/Treatment
"Control Group" 15 non-obese participants considered "metabolically-healthy" : "control group"
Obese group (Ob) 15 severely obese participants, candidates for bariatric surgery, but without T2D: "obese group" (Ob)
Obese and Type 2 Diabetes group (ObD) 15 participants who are both severely obese, candidates for bariatric surgergy and diagnosed with T2D: "obese and diabetic group" (ObD).

Outcome Measures

Primary Outcome Measures

Metagenomic analysis [1 month]
Single time point analysis of jejunal or colonic mucosal-associated and fecal microbiota. Microbiota will be analysed through 16S rRNA gene sequencing as well as shotgun metagenomic sequencing of the different samples. We will examine if jejunal microbiota abundance is decreased in subjects with obesity and obesity + type 2 diabetics compared to lean subjects. Based on metagenomic sequencing data, the number of bacterial genes will be estimated and compared between groups. We will examine the distance of bacterial layer in the mucus from intestinal epithelial cells in people with T2D as compared to people without T2D and lean subjects.

Secondary Outcome Measures

Clinical associations with metagenomic analysis [1 month]
Single time point analysis : Investigation of the correlations between jejunal microbiota or mucosal-associated microbiota and clinical parameters. Secondary objectives are to analyse the relationship between jejunal microbiota/mucus-associated microbiota and metabolic health, inflammation, lifestyle and mental health that will be evaluated through extensive bio-clinical phenotyping and will include: Metabolic phenotype (serum) Systemic inflammation status and Entero and Neuroendocrine markers (serum and biopsies) Anthropometric measurements Histological analysis of the jejunal biopsy obtained during endoscopy and colonoscopy Lifestyle factors collected through lifestyle questionnaires: Medical history questionnaires Dietary patterns Physical activity Smoking habits Psycho-emotional health and Quality of Life

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

General Inclusion Criteria:
Aged between 18 and 60 years;
Ability to understand and provide informed consent (in French);
Ability and willingness to meet the required schedule and study procedures;
Group-Specific Inclusion Criteria:
Control Group

Inclusion criteria for the participants from the Control group are:

Presence of Gastroesophageal Reflux Disease symptoms or gastric discomfort.
BMI [19kg/m² < BMI <25 kg/m²]
Match age and sex to the patients from the Ob and ObD groups.
Only patients with normal glucose tolerance (NGT), glucose tolerance (IGT) and/or fasting glucose (IFG) and an HbA1c < 6.5 % will be included in this group.
Ob Group

Inclusion criteria for the participants from Ob and ObD groups are:

● Candidate for bariatric surgery and meet the HAS criteria (Haute Autorité de Santé, 2009) :

IMC ≥ 40 kg/m² without comorbidities Or IMC≥ 35 kg/m² with at least one obesity-related comorbidity (i.e.: Hypertension, Dyslipidemia, Obstructive Sleep Apnea, Joints Disease, non-alcoholic steatohepatitis, excluding T2D)
Weight stable for at least 2 months
No treatment for metabolic health complications, no previous obesity surgery, no obesity treatment drug.
No monogenic form of obesity (Hebebrand et al., 2017)
ObD Group

Inclusion criteria for the participants from ObD groups are:

Candidate for bariatric surgery with T2D
At least one obesity-related comorbidity including T2D
Fasting plasma glucose (FPG) ≥7 mM (=1.26g/l) or
Participants with HbA1c ≥ 6.5% (48 mmol/mol)
All stages of albuminuria

Exclusion Criteria:

General Non-inclusion Criteria:
Treatment for the previous 12 week that could
alter gastrointestinal motor function (e.g. opioids, prokinetics, anticholinergics, laxatives),
acidity (PPI, H2RA)
microbial population (e.g.: antibiotics, probiotics)
immunosuppressants (eg: calcineurin inhibitors, corticosteroids, biological agents, etc.).
use of weight-loss drug or dietary intervention aiming to lose weight;
Altered anatomy of the esophagus, stomach, small or large intestine due to prior gastrointestinal surgery (exceptions include appendectomy or cholecystectomy more than 3 months prior to enrollment) or other reasons;
Any abdominal or pelvic surgery within the past 3 months;
Diverticulitis, diverticular stricture, or other intestinal strictures.
Intestinal resection of the gastrointestinal tract
Previous history of gastric bezoar or gastroparesis
Acute or chronic inflammatory bowel disease or infections diseases (i.e.: VHC, VHB, VIH, etc.)
Abdominal or pelvic radiotherapy or abdominal cancer
Colorectal cancer, either known or not
Dysphagia, eosinophilic esophagitis, esophageal stricture, or other swallowing disorder
Organ Transplantation and patients on Immunosuppressive Therapy
Severe kidney failure and/or patients on dialysis therapy (serum creatinine > 150 μmol/l or eGFR < 60 ml/min per 1.73 m2 body surface area)
CVD, endocrine, renal or other chronic disease likely to affect motility.
Colon cleansing preparation during the last 1 month
No < 3 bowel movements per week
Females of childbearing age who do not practice birth control and/or are pregnant or lactating
Participants non-affiliated to the French national health scheme
Participants who are already included in a clinical study which implies testing any pharmaceutical drug.
Participants who do not understand the research procedures those who are institutionalized, or who unable to give informed consent
Participants placed under legal protection
Patients with drug addiction
Antibiotherapy 3 months preceding the endoscopy
Weight variation (diminution or increase) > 5kg in the last 3 months
Specific non-inclusion Criteria
Ob and ObT2D Group
Usual contraindication for bariatric surgery;