Impact Of The Gut Microbiota On Host Cells Energy Metabolism in Health And In Inflammatory Bowel Disease
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-50
SponsorAssistance Publique - Hôpitaux de Paris
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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
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
Disqualifiers
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)
Trial design
Design model
Parallel
Treatments tested in this trial
Vancomycin /Amphotericin B (Fungizone®) /Gentamicine 80 mg
Drug7 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
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.
Treatment groups
45 Participants
are divided into 2 treatment groupsGroup A: Healthy volunteersExperimental treatment 1 intervention
Group B: Patients with IBDExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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 * For healthy adults, this analysis will be performed on blood sample at day 0 (v1, before antimicrobial treatment onset) and at day 7 (v2, last day of the antimicrobial treatment). * For patients with IBD this analysis will be performed on blood sample at day 0 (v1). 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
Time frame
Healthy volunteers : 7 days/ IBD patients : 1 daySecondary outcomes
1
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. * Similar analysis will be performed on each urine samples emitted during day 0 (v1) and day 7 (v2) for healthy adults and day 0 (v1) for patients with IBD. * Similar analysis will be performed on each fecal samples emitted during day 0 (v1) and day 7 (v2) for healthy adults and day 0 (v1) for patients with IBD. Stool emitted on day 1 and on day 8 will be also collected for analysis.
Time frame
Healthy volunteers : 7 days/ IBD patient : 1 day2
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.
Time frame
Healthy volunteers : 7 months and 8 days/IBD patient : 4 weeks and 2 daysSponsors and contacts
Click on the lead sponsor to view all of their trials.
Assistance Publique - Hôpitaux de Paris
Lead sponsor
INSERMUMR938
Collaborator
CRB SAT APHP.SU Saint-Antoine hospital
Collaborator
Source ClinicalTrials.gov