Is metabolic health in humans related to gut permeability?

There is growing evidence that gut permeability (or a *leaky gut*) can be
linked to metabolic health and might therefore be involved in development of
metabolic disorders related to the metabolic syndrome. Recently, a multi-sugar
(MS) permeability test was developed to more accurately assess gut permeability
compared to the classical dual sugar tests. Next to this MS permeability test,
also other potential leaky gut-related markers in blood (LPS, LBP (LPS-binding
protein), sCD14 (soluble CD14), leptin and zonulin) that are related to
metabolic health could provide additional information on gut permeability. In
the Permeable study, we want to expand our knowledge on if and how the
intestinal barrier relates to metabolic health. This knowledge could be
fundamental to further identify and explore compounds that can strengthen the
intestinal barrier and thereby contribute to metabolic health and the
prevention of metabolic disorders.

The primary objective of the study is to compare gut permeability in metabolic
healthier and metabolic unhealthier subjects by performing a MS permeability
test. The secondary objectives are to study the correlation between gut
permeability assessed by a MS permeability test and 1) metabolic health status
and 2) previously identified potential leaky gut markers LPS, LBP, sCD14,
leptin and zonulin.

The Permeable study is an observational study, in which gut permeability is
assessed by a MS permeability test. The MS test will be performed with and
without an acetylsalicylic acid challenge and therefore each subject will visit
the research facility twice. On the day of the MS test, first weight and height
are measured and a fasting blood sample is collected. Subsequently, subjects
consume 200 ml MS mix solution (containing sucrose, lactulose, rhamnose,
sucralose and erythritol) and urine is collected in three fractions (0-2 hours,
2-5 hours and 5-24 hours). Five hours after drinking the MS mix, subjects
receive a standardized lunch and then urine collection continues till the next
morning at home, where they are allowed to eat normally (with restriction of
lactulose, rhamnose, sucralose and erythritol, alcohol, caffeine (including
tea) and spicy foods). During the second visit, at least 4 days later, the same
procedures are repeated, except the subjects will consume acetylsalicylic acid
before the MS test (1000mg in the evening and 1000mg in morning prior to the
test).

The burden for participants in this study is relatively low. They only have to
visit the research facilities twice. However, participants might experience
some level of burden from fasting overnight and fasting during the first 5
hours of the MS permeability test. Also the temporary deprivation of caffeine
and alcohol might elicit an unpleasant feeling for some of the participants.
The risks for participation are very small. A fingerstick measurement (once)
and drawing blood (twice) can be a little painful and in exceptional cases, a
bruise may occur. The amount of blood that is drawn from participants is
minimal (10-12ml) and it is not expected that this gives rise to problems for
adults. Only very occasionally, a hypo- or hyperglycaemic response may occur
after drinking the MS mix solution and some people might experience
gastrointestinal complaints after intake of acetylsalicylic acid .
There are no direct benefits for the participants, except for the fact that
they receive information about their metabolic health profile.