Investigating gut microbiota in metabolic diseases like diabetes and obesity

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

This study is trying to see how the bacteria in the gut of people with obesity and diabetes might affect their health.

Quick facts

• Study type: Observational
• Enrollment: 90 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France (Government)
• Locations: 1 site (Paris)
• Trial ID: NCT05186389 on ClinicalTrials.gov

What this trial studies

This observational study aims to explore the microbiota associated with the jejunum and colonic mucosa in individuals suffering from metabolic diseases, specifically focusing on diabetes mellitus and obesity. The study will recruit a total of 90 participants divided into two parts: Je-MiMe and Col-MiMe, each consisting of three groups: a control group, an obese group, and an obese group with type II diabetes. Participants will undergo assessments to identify the microbiota present in their gastrointestinal tract, which may provide insights into the role of these microorganisms in metabolic health.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18-60 with obesity or type II diabetes, as well as healthy controls with specific BMI and glucose tolerance criteria.

Not a fit: Patients outside the age range of 18-60 or those with significant comorbidities unrelated to obesity or diabetes may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could enhance understanding of the gut microbiota's role in metabolic diseases, potentially leading to new therapeutic strategies.

How similar studies have performed: While there have been studies examining the role of microbiota in metabolic diseases, this specific approach focusing on jejunal and colonic microbiota is relatively novel.

Eligibility criteria

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;

Where this trial is running

Paris

• Hôpital Privé des Peupliers, 8 Place de l'Abbé Georges Hénocque, 75013 — Paris, France (Recruiting)

Study contacts

• Study coordinator: Emilie Steinbach, MSc

Conditions Diabetes Mellitus; Obesity; Metabolic Disease; microbiota; endoscopy; colonoscopy; obesity; type II diabetes