metabolic syndrome, obesity, diabetes mellitus type 2, insulin resistance, low-grade inflammation, gut dysbiosis, gut microbiome metabolic syndrome, obesity, overweight, (type 2) diabetes, microbiome
Conditions
Interventions
Study participants will be randomized to receive either LFMC or placebo. LFMC are produced from rigorously screened, healthy lean donors. A loading dose of 21 capsules will be given at baseline, follo
a second loading dose will be administered at mid-intervention. Placebo capsules are visually identical and contain inert filler.
Sponsors
Amsterdam UMC
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Study participants: - Men (18-70 yrs) / postmenopausal women (=70 yrs); - Obese (BMI =30); - Insulin resistant (HOMA-IR =2.5); - Treatment/medication-naïve.Fecal donors: - Men (18-70 yrs) / postmenopausal women (=70 yrs); - Healthy, normal weight (BMI 18.5-25).
Exclusion criteria
Exclusion criteria: Study participants - Recent (<3 months) use of microbiota-altering or immunosuppressive agents; - Chronic inflammatory, autoimmune, or gastrointestinal disease; - Contraindication to endoscopy or bone marrow aspiration; - Active smoking or excessive alcohol consumption.Fecal donors - Recent use of relevant medication (e.g. antibiotics); - Relevant chronic disease; - Presence or increased risk of transmissible disease; - Abnormal blood or fecal screening results; - Contraindication to endoscopy or bone marrow aspiration.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Between-group differences (LFMC vs. placebo) in changes in bone marrow HSPC characteristics, assessed before and after intervention, in relation to insulin resistance (measured by continuous glucose monitoring [CGM]). HSPC characteristics will be evaluated through:Gene expression profiles (single-cell RNA sequencing);Turnover dynamics (assessed by oral deuterated water [D2O] labeling and mass-spectrometry quantification of DNA enrichment);HSPC subset frequencies (FACS);Functional phenotyping of HSPC subsets (FACS). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints include changes in gut microbiota composition (metagenomics), small-intestinal mucosal immunity (scRNA), duodenal histology and gut barrier indices, systemic inflammatory and cardiometabolic markers, PBMC phenotypes, and plasma metabolomics. Donor-derived bone marrow, duodenal biopsies, blood and stool samples will provide benchmark data for comparison with MetSyn participants. | — |
Countries
Netherlands
Contacts
Public ContactM. Tweel
Amsterdam UMC
Outcome results
None listed