Gut bacteria and immune-cell energy in people with IBD and healthy adults

Impact Of The Gut Microbiota On Host Cells Energy Metabolism in Health And In Inflammatory Bowel Disease

We will test whether gut bacteria change how immune cells use energy in people with Crohn's disease or ulcerative colitis and in healthy adults by using a short antibiotic course and a labeled fiber.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 18 Years to 50 Years
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (Academic / other)
• Locations: 1 site (Paris)
• Trial ID: NCT07300553 on ClinicalTrials.gov

What this trial studies

This phase 2 interventional study compares immune-cell energy metabolism in IBD patients and healthy volunteers using SCENITH metabolic profiling. Healthy volunteers are sampled before and after a short oral antibiotic regimen, while IBD patients are sampled once. All participants receive 13C-labeled inulin so researchers can track how gut bacteria break down and transfer that nutrient; blood, urine, and stool samples and stool DNA/RNA will be analyzed. The protocol includes administration of antibiotics (vancomycin, amphotericin B, gentamicin) for the microbiota perturbation in healthy volunteers and metabolic tracing with labeled inulin.

Who should consider this trial

Good fit: Ideal candidates are adults with diagnosed Crohn's disease or ulcerative colitis, or healthy adults aged 18–49 with BMI between 17 and 25 who can tolerate a short antibiotic course and provide blood, urine, and stool samples.

Not a fit: People who cannot take the study antibiotics, are pregnant, are outside the age or BMI ranges, or cannot provide required samples are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this work could reveal microbiota-driven changes in immune-cell metabolism that point to new diagnostic markers or therapeutic targets for IBD.

How similar studies have performed: Prior research has linked the gut microbiota to immune function, but applying SCENITH profiling together with 13C-inulin tracing to map metabolic transfers is relatively novel.

Eligibility criteria

Inclusion Criteria:

Healthy volunteer

1. Age ≥ 18 years and \< 50 years
2. 17 kg/m² \< body mass index \< 25 kg/m² (microbiota modified based on BMI, (Le Chatelier et al., 2013)
3. For women, female of child-bearing age with an active contraception (hormonal, intrauterine device, bilateral tubal occlusion, sexual abstinence\*) and this during at least the period of treatment (up to v2) \*Sexual abstinence is defined as refraining from heterosexual intercourse from providing consent until V3. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant

   * A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH), level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient
4. Regular bowel movement defined as at least 1 stool every other day and maximum 3 stools per day
5. Patient with health insurance (AME except)
6. Informed Written consent Patient with IBD

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1. Age ≥ 18 years and \< 50 years
2. Crohn's Disease (Excepting disease involving only the upper GI tract) or ulcerative colitis (excepting disease involving only the rectum), according to the Lennard-Jones criteria for at least 6 months (15 patients with Crohn's disease and 15 with ulcerative colitis will be recruited)
3. Patient in steroid-free clinical remission for at least 6 months (for Crohn's disease: CDAI \<150 the week before inclusion, for ulcerative colitis: Partial Mayo Clinic score of 0 or 1).
4. 17 kg/m² \< body mass index \< 25 kg/m²
5. Female of child-bearing age with an active contraception. Efficient contraception include oral contraception, intrauterine devices hormonal device, intrauterine hormone-releasing system, sterilization method and other forms of contraception with failure rate \<1%)

   \*\* A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.

   A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient
6. Regular bowel movement defined as at least 1 stool every other day and maximum 3 stools per day
7. Patient with health insurance (AME except)
8. Informed Written consent

Non inclusion Criteria:

Healthy volunteers

1. Significant chronic disease and particularly chronic gastrointestinal diseases, type 1 and type 2 diabetes, renal alteration
2. Curative long-term treatment
3. Pregnant or breastfeeding women\*\* \*\* A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.

   A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
4. blood donation in the 3 months before the study
5. Taking antibiotic or antifungal (oral) in the previous 3 months before planned day 0 (V1)
6. probiotics in the month preceding day 0 (V1),
7. consumption of a low-calorie diet or any other special diet (except vegetarian) in the month before day 0
8. abdominal surgery in the past (except for appendectomy)
9. allergy against the antibiotics and antifungal treatment used in this study or to their excipients
10. contra-indications to the administration of gentamicin (refer to SmPC)
11. Participation in any other interventional study
12. Patients under legal protection Patients with IBD

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1. Pregnant or breastfeeding women
2. blood donation in the 3 months before the study
3. Taking antibiotic or antifungal (oral) in the previous 3 months before planned day 0
4. probiotics in the month preceding day 0 and during the study,
5. Ileal resection \> 50cm or colectomy
6. Diagnosis of Crohn's disease restricted to the upper gastrointestinal tract (oesophagus, stomac, duodenum, jejunum)
7. Diagnosis of ulcerative colitis restricted to the rectum.
8. Current stoma (Ileostomy or a colostomy) or stoma in the last 6 months or any other intra-abdominal surgery within 3 months prior to inclusion
9. Participation in any other interventional study
10. Patients under legal protection

Exclusion Criteria:

Healthy volunteers :

* Clinically significant abnormal serum/ plasma levels of electrolytes, creatinine, liver enzymes, thyroid stimulating hormone or blood cell count at the biological check-up of the visit v0 (screening and inclusion)
* Infectious episode requiring antimicrobial treatment since V0
* Severe diarrhea (increase of seven or more stools per day over baseline)

Patients with IBD - Infectious episode requiring antimicrobial treatment since V0

\- IBD flare

Where this trial is running

Paris

• Gastroenterology Department Saint Antoine Hospital, — Paris, France (Recruiting)

Study contacts

• Principal investigator: Harry SOKOL, PU-PH — Assistance Publique - Hôpitaux de Paris
• Study coordinator: Harry SOKOL, PU-PH

Conditions IBD; Crohn Disease; Ulcerative Colitis; Energy Metabolism; Gut Microbiota; Healthy volunteers; Patients with IBD; SCENITH analysis