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

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

Inflammatory Bowel Disease (IBD) often leads to poor disease control and reduced quality of life. Changes in the gut microbiota may disrupt the energy metabolism of immune cells, contributing to IBD.

This study will examine how gut microbiota affects immune cell metabolism in healthy adults and IBD patients. Healthy volunteers will be tested before and after a short antibiotic treatment, while IBD patients will be tested once.

Energy metabolism will be measured using SCENITH, a method that analyzes metabolic activity in blood immune cells.

Participants will also receive a special form of fiber (13C-labeled inulin) to track how gut bacteria break down and use this nutrient. Blood, urine, and stool samples will be analyzed to follow the metabolic fate of inulin. DNA and RNA from stool will be studied to identify which bacteria metabolize the labeled fiber.

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

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

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