Combining Fasting and Fibre Interventions to Optimise Their Gut Microbiome-mediated Health Benefits

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.

Conditions

• Fasting
• Dietary Fibre
• Gut Microbiome
• Metabolism Changes
• Overweight , Obesity

Interventions

DIETARY_SUPPLEMENT

Fibre 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_SUPPLEMENT

Control 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 & Collaborators

• King's College London, Faculty of Life Sciences & Medicine, Department of Nutritional Sciences, London, United Kingdom

  collaborator UNKNOWN

• Leiden University Medical Center, Department Leiden University Center for Infectious Diseases, 2333ZA, Leiden, Netherlands

  collaborator UNKNOWN

• TNO, Department Microbiology & Systems Biology, 2333 BE Leiden, Netherlands

  collaborator UNKNOWN

• Università degli Studi di Milano, Department of Pharmacological and Biomolecular Sciences Rodolfo Paoletti, Milan, Italy

  collaborator UNKNOWN

• Department of Cardio-Thoracic-Vascular Diseases, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

  collaborator UNKNOWN

• Buchinger Wilhelmi Development & Holding GmbH

  lead OTHER

Principal Investigators

• Andrea Siegler, Dr. med. · Buchinger Wilhelmi Development & Holding

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2026-09-01

Primary Completion

2027-02-28

Completion

2027-03-31

Countries

• Germany

Study Locations