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| Name | Class |
|---|---|
| INSERMUMR938 | UNKNOWN |
| CRB SAT APHP.SU Saint-Antoine hospital | UNKNOWN |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy volunteers | Experimental | Healthy volunteer will be seen by a physician from the CRC-Est in LRIPH Saint-Antoine to verify their eligibility and collect their written consent. The baseline visit (V1) takes place within 4 weeks after the inclusion visit (V0). Antimicrobial treatment will be provided to the participant (7/8 days treatment). V2 takes place 7 days after baseline visit after the antimicrobial treatment For each visit (V1 and V2) the participants will be seen by a research physician and nurse after an overnight fast. Blood sample (for SCENITH analysis) will be perfomed. Then, participants will receive a standard breakfast with 10g 13C-labeled inulin, which serves as a model fermentable substrate. Blood samples (8mL) will be then collected every hour between 2 and 10h after consumption of the breakfast. All urines and stool samples emitted during the day D0 will be collected (and time recorded). Follow up at D2 to D3 post V1 will be done by a phone interview by CRT or nurse with the help and validati |
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| Patients with IBD | Experimental | IBD patients will be seen by a gastroenterologist from the Gastroenterology department of the Saint-Antoine hospital or physician from the CRC-Est in LRIPH or the gastroenterology department of Saint Antoine to verify their eligibility, and collect their written consent during a usual follow up visit. The baseline visit (V1) takes place within 4 weeks after the inclusion visit (V0). The patients will be seen by a research physician and nurse after an overnight fast. Blood sample (for SCENITH analysis) will be perfomed. Then, participants will receive a standard breakfast with 10g 13C-labeled inulin, which serves as a model fermentable substrate. Blood samples (7mL) will be then collected every hour between 2 and 10h after consumption of the breakfast. All urines and stool samples emitted during the day D0 will be collected (and time recorded). The patient will also receive a kit for fecal collection at home to be done the day before v1. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vancomycin /Amphotericin B (Fungizone®) /Gentamicine 80 mg | Drug | 7 days treatment taken over 8 calendar days). The first intake will take place just before leaving the hospital on the evening of day 0. A precise schedule will be provided for the antibiotics intakes, with the last intake in the afternoon on day 7 (on day 7, only 3 intakes of antibiotics: morning, noon and afternoon): Vancomycin VIATRIS 500 mg for injection or oral administration Dose: 250mg x4 daily orally Amphotericin B (Fungizone®) Bottle 10% (4000mg/40ml) oral solution Dose 500mg x4 (20ml) daily orally Gentamycine 80 mg/2 ml solution (hospital compounding) Dose 80mg x4 daily orally |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate the impact of the gut microbiota, and of its alteration in inflammatory bowel disease, on peripheral immune cells energy metabolism | Energy metabolism of major immune cell types for peripheral blood will be assessed on a blood sample
The energy metabolism will be assessed by single-cell energetic metabolism by profiling translation inhibition (SCENITH) approach (Argüello et al., 2020). SCENITH is a flow cytometry-based approach allowing to functionally profile energy metabolism with single-cell resolution from a simple blood sample | Healthy volunteers : 7 days/ IBD patients : 1 day |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate the impact of the gut microbiota and its alteration in inflammatory bowel disease on the fate of microbiota-derived carbon sources in host cells | we will use a strategy based on stable isotope probing (SIP). The participants will receive orally food grade inulin from Chicory (2% labelled with 13C) at H0 on day 0 (v1) and day 7 (v2) for healthy adults and day 0 (v1) only for patients with IBD. The incorporation of 13C in metabolites will then be assessed Targeted (TCA cycle and glycolysis intermediates and fatty acids) and untargeted metabolomics will be performed on blood samples obtained every hour from 2 h to 10 h post inulin intake on day 0 (v1) and day 7 (v2) for healthy adults and day 0 (v1) only for patients with IBD.
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Inclusion Criteria:
Healthy volunteer
Age ≥ 18 years and < 50 years
17 kg/m² < body mass index < 25 kg/m² (microbiota modified based on BMI, (Le Chatelier et al., 2013)
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
Regular bowel movement defined as at least 1 stool every other day and maximum 3 stools per day
Patient with health insurance (AME except)
Informed Written consent Patient with IBD
Age ≥ 18 years and < 50 years
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)
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).
17 kg/m² < body mass index < 25 kg/m²
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
Regular bowel movement defined as at least 1 stool every other day and maximum 3 stools per day
Patient with health insurance (AME except)
Informed Written consent
Non inclusion Criteria:
Healthy volunteers
Significant chronic disease and particularly chronic gastrointestinal diseases, type 1 and type 2 diabetes, renal alteration
Curative long-term treatment
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.
blood donation in the 3 months before the study
Taking antibiotic or antifungal (oral) in the previous 3 months before planned day 0 (V1)
probiotics in the month preceding day 0 (V1),
consumption of a low-calorie diet or any other special diet (except vegetarian) in the month before day 0
abdominal surgery in the past (except for appendectomy)
allergy against the antibiotics and antifungal treatment used in this study or to their excipients
contra-indications to the administration of gentamicin (refer to SmPC)
Participation in any other interventional study
Patients under legal protection Patients with IBD
Exclusion Criteria:
Healthy volunteers :
Patients with IBD - Infectious episode requiring antimicrobial treatment since V0
- IBD flare
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Harry SOKOL, PU-PH | Contact | 00 33 1 49 28 31 62 | harry.sokol@aphp.fr | |
| Mélissa MONTIL, Praticien attaché | Contact | 00 33 1 71 97 0810 | melissa.montil@aphp.fr |
| Name | Affiliation | Role |
|---|---|---|
| Harry SOKOL, PU-PH | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Gastroenterology Department Saint Antoine Hospital, | Recruiting | Paris | 75012 | France |
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| Inulin/Inulin C13 | Dietary Supplement | - INULIN ; food grade inulin from Chicory (2% labelled with 13C) at H0 on day 0 (v1) and day 7 (v2) for healthy adults and day 0 (v1) only for patients with IBD. |
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| Healthy volunteers : 7 days/ IBD patient : 1 day |
| Identify the intestinal bacteria involved in this process | we will use SIP-DNA and SIP-RNA sequencing approaches (Fortunato and Huber, 2016; Neufeld et al., 2007; Ziels et al., 2018). DNA and RNA will be extracted from each fecal samples obtained (see above). Labeled DNA/RNA will be separated by density gradient centrifugation. The "heavier" labeled nucleic acid fractions, corresponding to microorganisms that metabolized labeled inulin and incorporated labeled atoms into their nucleic acids, will undergo 16s and/or shotgun sequencing to identify the inulin-metabolizing taxa. | Healthy volunteers : 7 months and 8 days/IBD patient : 4 weeks and 2 days |
| ID | Term |
|---|---|
| D003424 | Crohn Disease |
| D003093 | Colitis, Ulcerative |
| ID | Term |
|---|---|
| D015212 | Inflammatory Bowel Diseases |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |
| D003092 | Colitis |
| D003108 | Colonic Diseases |
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| ID | Term |
|---|---|
| D014640 | Vancomycin |
| D000666 | Amphotericin B |
| D007444 | Inulin |
| ID | Term |
|---|---|
| D006020 | Glycopeptides |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D013213 | Starch |
| D005936 | Glucans |
| D001704 | Biopolymers |
| D011108 | Polymers |
| D046911 | Macromolecular Substances |
| D004040 | Dietary Carbohydrates |
| D005630 | Fructans |
| D011134 | Polysaccharides |
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