Dietary Fibre, Fasting, Gut Microbiome, Metabolism Changes, Overweight , Obesity
Conditions
Keywords
long-term fasting, fasting, continuous glucose monitoring, fibre supplementation, gut microbiome, metabolic health, resistant starch IV, metabolomics, ketosis, extracellular vesicles
Brief summary
This study builds on the knowledge that fasting provides metabolic health benefits and that prebiotic interventions can enhance the gut microbiome's metabolic output to likewise improve host health. Whether long-term fasting and dietary fibre interventions could be combined to achieve synergistic improvements in host metabolic health is however unknown. The goal is to provide a proof of concept in a human trial that supplementing 10±4 days fasting with dietary fibre synergistically improves metabolic outcomes via gut microbiome-mediated effects. To assess this, we aim to analyse gut microbiome changes, functional outputs, and key metabolic markers such as butyrate production, glycaemic control and ketosis. The randomised controlled trial includes 75 participants and has two arms: one involving fasting with fibre supplementation (n = 50) and one involving fasting without fibre supplementation (n = 25). All participants will undergo a fasting period of 10±4 days according to the Buchinger Wilhelmi protocol, followed by a stepwise reintroduction of food of up to 4 days. As dietary fibre we will use maize-derived resistant starch type IV, selected based on its ability to stimulate beneficial gut microbes like Oscillibacter and corn starch as placebo. Two main visits will be conducted: before and at the end of the fasting period. During these visits, blood and stool samples will be collected, and questionnaires will be completed. Additionally, daily measurements of anthropometric parameters and well-being will be recorded. Stool samples will also be collected one month afterwards as a follow-up. Participants' metabolic health will be evaluated through various clinical parameters (e.g., body measurements, blood pressure, glycaemic control, ketones, well-being). Additionally, multi-omics data, including metagenomics and metabolomics, will provide insight into the composition of the microbiome, as well as its outputs and functions. Furthermore, the effects of fasting on extracellular vesicles in blood will be explored.
Interventions
DIETARY_SUPPLEMENTFibre Arm
10±4 days of fasting according to the Buchinger Wilhelmi fasting protocol, followed by a structured food reintroduction period, combined with 20 g/day of maize-derived resistant starch type IV.
DIETARY_SUPPLEMENTControl Arm
10±4 days of fasting according to the Buchinger Wilhelmi fasting protocol, followed by a structured food reintroduction period, combined with 1.2 g/day of corn starch placebo.
Sponsors
Buchinger Wilhelmi Development & Holding GmbH
Buchinger Wilhelmi Clinic, 88662 Überlingen, Germany
King's College London, Faculty of Life Sciences & Medicine, Department of Nutritional Sciences, London, United Kingdom
Leiden University Medical Center, Department Leiden University Center for Infectious Diseases, 2333ZA, Leiden, Netherlands
TNO, Department Microbiology & Systems Biology, 2333 BE Leiden, Netherlands
Università degli Studi di Milano, Department of Pharmacological and Biomolecular Sciences Rodolfo Paoletti, Milan, Italy
Department of Cardio-Thoracic-Vascular Diseases, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Men and women * Age: 18-65 years old * Fasting for 10±4 days at the Buchinger Wilhelmi clinic in Überlingen * BMI ≥ 25 kg/m² * Signed informed consent
Exclusion criteria
* intake of antibiotics up to 2 months prior the study * regular intake of pre-, post- and probiotics up to 2 months prior the study * diagnosed Crohn's disease, Ulcerative colitis, IBD, coeliac disease * medicated high blood pressure * diagnosed diabetes mellitus type I * medicated diabetes mellitus type II * diagnosed kidney stone * active malignant disease * known substance addiction * pregnancy or breastfeeding * diagnosed with cachexia, anorexia nervosa, advanced kidney, liver or cerebrovascular insufficiency * inability to sign the informed consent * participation in another study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Abundance of butyrate-producing gut bacteria | Baseline (T0) and end of the 10±4-day fasting period (T1) | Change in the relative abundance of butyrate-producing gut bacteria assessed by metagenomic profiling of faecal samples. |
| Change in fasting venous plasma glucose | Baseline (T0) and end of the 10±4-day fasting period (T1) | Fasting venous plasma glucose concentration measured by clinical laboratory analysis (mmol/L). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in body weight | Baseline (T0) and end of the 10±4-day fasting period (T1) | Body weight (kg) measured as part of the clinical health assessment. |
| Change in body mass index | Baseline (T0) and end of the 10±4-day fasting period (T1) | Body mass index calculated from measured body weight and height (kg/m²). |
| Change in waist circumference | Baseline (T0) and end of the 10±4-day fasting period (T1) | Waist circumference (cm) measured as part of the clinical health assessment. |
| Change in HbA1c | Baseline (T0) and end of the 10±4-day fasting period (T1) | HbA1c (mmol/mol) measured by clinical laboratory analysis of venous blood. |
| Change in HOMA index | Baseline (T0) and end of the 10±4-day fasting period (T1) | HOMA index calculated from fasting plasma glucose and fasting insulin concentrations. |
| Change in fasting venous insulin | Baseline (T0) and end of the 10±4-day fasting period (T1) | Fasting venous insulin concentration (pmol/L) measured by clinical laboratory analysis. |
| Change in glycaemic control assessed by continuous glucose monitoring | From Day 1 through Day 14 | Glycaemic control assessed by blinded continuous glucose monitoring using the FreeStyle Libre 3 system, with glucose values recorded at 1-minute intervals (mmol/L). |
Countries
Germany
Contacts
CONTACTElena Katharina Stroppel
PRINCIPAL_INVESTIGATORAndrea Siegler, Dr. med.
Buchinger Wilhelmi Development & Holding
Outcome results
None listed