The PROFUN study: PROtein Fermentation UNraveled - Exploring the relationship between digestibility and metabolite production.

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
we will study protein fermentation 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.

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.

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.

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

This study is related to a broad general population. There are minor risks for
the healthy research subjects of this study. The diets are composed by licensed
dieticians of Wageningen University & Research. Subjects that participate in
this study will invest approximately 31 hours in the study. They will visit the
research facility 4 times: information and screening, baseline period, Test day
during dietary intervention 1, and Test day during dietary intervention 2. The
blood collection by a venous catheter for a half day during both diet
interventions could be a burden and placement of the catheter could cause
bruising. Participants will have to swallow 5 GISMO GEN1 ingestibles in total
during the study. After taking the GISMO GEN1 ingestible, participants will
have to collect all of their feces for several days to confirm the excretion of
the capsule and to collect fecal samples for analyses.
If the ingestible is visible on the X-ray, 7 days later (14 days after
administration) another X-ray is made. If the ingestible did not exit the GIT
via feces after 14 days, a bowel cleanse with laxatives is advised. In the rare
case that a bowel cleanse did not lead to excretion of the ingestible, an
endoscopic or surgical treatment is recommended depending on the location of
the ingestible. The expenses for such treatments will be covered by the
research team.
The participants do not directly benefit from the study but receive a financial
compensation of ¤395,- after completing the study. Traveling expenditures will
also be covered. Furthermore, all foods will be provided for 14 days during the
intervention trial.