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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
45
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
\- 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.
Gastroenterology Department Saint Antoine Hospital,
Paris, France
RECRUITINGEvaluate 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 day
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 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.
Time frame: Healthy volunteers : 7 months and 8 days/IBD patient : 4 weeks and 2 days
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.