The effects of the synbiotic Ecologic 825/scFOS on intestinal barrier function and immune modulation

The intestine contain large amounts of bacteria that are essential for proper
functioning of the digestive system. They are involved in the breakdown of
nutrients, and in the immune system of the body. Little is known about the
exact health effects of supplementation of "good" bacteria, also called
probiotics. Research has shown that supplementation of probiotics in the
presence of prebiotics, a so-called synbiotic supplement, may have more
pronounced beneficial effects on human health than supplementation of pro- or
prebiotics alone. In this study, we will determine the effects of a new
synbioticum on the bacterial composition of intestinal fluid and feces. We will
also examine the effects of the synbioticum on intestinal barrier function and
the immune system of the body.

The primary objective of this study is to assess the effects of the symbiotic
Ecologic 825/scFOS on intestinal epithelial permeability.

This study has five secondary objectives:
1. The first secondary objective of this study is to study the microbiota
composition in healthy humans at three different points along the small
intestinal tract (duodenum, jejunum, ileum) using culture-independent
approaches.
2. The second secondary objective of this study is to assess the impact of
supplementation of the synbiotic Ecologic® 825/scFOS on the population dynamics
and functionality of the microbiota along the gastrointestinal tract (duodenum,
jejunum, ileum and feces) using culture-independent approaches. This includes
potential stimulation of CRIB, as determined by 16S rRNA gene copies counts in
ileum fluid.
3. The third secondary objective of this study is to assess the effects of the
synbiotic Ecologic® 825/scFOS on immune modulation, by determining the levels
of several cytokines and chemokines in blood plasma (TNFa, IL-1b, IL-6, IL-8,
IL-17, MCP-1 and MIP-1a).
4. The fourth secondary objective of this study is to determine whether ileal
CRIB counts associate with any of the parameters mentioned under the primary
objective, and under the third secondary objective.

During a 17-days period, all patients will consume supplements containing
either 1) probiotics (mix of several species called Ecologic 825) and
scFOS/supplement ; 2) placebo during breakfast and during dinner. Prior to the
start of the supplementation period, several baseline measurements will be
done. First, the microbial composition of the intestinal fluid in the proximal-
mid- and distal small intestine will be determined. To enable this, a
naso-ileal sampling catheter will be placed with the catheter tip located in
the ileum . After successful positioning of the catheter, 10 ml of intestinal
fluid will be sampled from each location by aspiration using a 20-ml syringe.
After sampling, the catheter will be removed by gently retracting the catheter.
On the same day, a blood sample will be obtained to measure parameters of the
immune system , and a fecal donation will be handed in by the subject, to
determine the effects of the intervention on microbial composition of feces. On
the next morning, small intestinal permeability will be assessed
non-invasively. Two days after this first permeability assessment, intestinal
permeability in a stressed condition will be determined using an indomethacin
challenge. The indomethacin challenge will compromise the gut. These two
subsequent measurements of intestinal permeability serve to obtain baseline
permeability values as references for the intervention values. After a 14-days
supplementation period, this whole procedure will be performed for a second
time conform protocol prior to intervention: (positioning of a naso-ileal
sampling catheter, sampling of small intestinal fluid on the next day together
with collection of blood and fecal samples, followed by a permeability test the
next morning and a last permeability test under stressed conditions two days
later.
Gastrointestinal symptoms and feelings of well-being will be scored every
second day prior to sleeping, by completing the symptom diary.

Positioning of a feeding catheter, to be applied for fluid sampling from the
small intestine.
Blood sampling.
Sugar test (consumption of sugar drink and collection of urine) for the
assewssment of intestinal barrier function.
Collection of feces.

During feeding catheter positioning, subjects will suffer from local discomfort
in the throat.
After positioning of the feeding catheter, tits exact location will be checked
using fluoroscopy. The radiation exposure is very small (total radiation
exposure during this study will maximally be 0.2 mSv effective dose), and will
not induce risks for these healthy volunteers.
A subject will spend 12.5 hrs in total to the participation in this study, over
a total study duration of 21 days.