Protein Fermentation Unraveled (PROFUN) - Exploring the Relationship Between Digestibility and Metabolite Production

Summary

Background of the study:

Protein intake is often higher than recommended in Western countries. This leads to increased amounts of protein flowing into the large intestine. Next to increased dietary protein intake, protein digestibility, and endogenous protein losses also affect the amount of protein entering the large intestine. However, these aspects have barely been studied, especially in humans. The large intestine is home to the largest bacterial ecosystem of the body. During the fermentation of protein by these bacteria (microbiota), metabolites are produced such as ammonia, branched-chain fatty acids, biogenic amines, phenolic compounds, indoles, and N-nitroso compounds. There is evidence that some of these metabolites could be harmful for gut epithelia, gastrointestinal health, and health in general after they enter blood circulation. In general, doing measurements inside the gastrointestinal tract is invasive. During this project the protein fermentation will be studied in the gastrointestinal tract using feces and urine, but also in situ using the GISMO GEN1 ingestible. This ingestible contains sensors to measure pH, ammonium, temperature, and redox potential.

Objective of the study:

The primary objectives of this study are:

1. To investigate the feasibility of the GISMO GEN1 System to monitor biomarkers in the gastrointestinal tract by studying the ingestible transit time, data coverage, participant experience, and serious adverse events (if applicable).
2. To study the effect of a 7-day high versus low digestible protein source present in the diet on protein fermentation in healthy subjects, measured by ammonia concentrations.

Study design:

The study is divided into 2 phases. In phase 1, preliminary feasibility of the GISMO GEN1 ingestible system will be assessed and the baseline measurements will be taken without any dietary restrictions. An interim analysis will be performed after phase 1 and only after a positive evaluation of the GISMO GEN1 System, the study will continue with phase 2.

Phase 2 is a randomized cross-over controlled feeding trial. Two diets will be used: one diet containing a high digestible protein source, and the other diet containing a low digestible protein source. Each diet will be given for 7 days, with a wash-out period in between. Measurements done during the dietary interventions will be compared to the other diet, and to the baseline measurements.

Study population:

15 healthy male or female volunteers, age 16 or older, BMI 18.5-30.

Intervention:

A high digestible protein diet (30 g/d whey protein) and a low digestible protein diet (30 g/d bovine plasma protein).

Primary study parameters/outcome of the study:

Ammonia as biomarker for protein fermentation, measured in feces and urine and in situ by the GISMO GEN1 ingestible.

Also, ingestible transit time, data coverage, participant experience, and serious adverse events.

Secundary study parameters/outcome of the study (if applicable):

Secondary study parameters include other protein fermentation related metabolites measured in feces, urine and blood; microbiome composition; transit time; absorption kinetics.

Conditions

• Protein Fermentation

Interventions

COMBINATION_PRODUCT

Protein digestibility

Two protein sources differing in digestiblity will be used in the dietary intervention to create a difference in protein flow into the large intestine, resulting in different levels of protein fermentation. Participants will swallow an ingestible that senses biomarkers related to protein fermentation.

Sponsors & Collaborators

• Stichting IMEC-NL

  collaborator OTHER

• Wageningen University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Model

CROSSOVER

Eligibility

Min Age

16 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2023-11-21

Primary Completion

2024-02-07

Completion

2024-02-07

Countries

• Netherlands

Study Locations