The role of intestinal microbiota and permeability in inflammation and in the pathogenesis of morbid obesity

Recently it has become evident that inflammatory processes are essential in the
development of in the development of obesity and obesity related disorders such
as IR/DMII, coronary diseases and non alcoholic fatty liver disease.{zie
referenties in het onderzoeksprotocol: Shoelson, 2006 #10}. Unfortunately, the
source of inflammation in the obese population remains unclear.
Based on animal studies and a few recent human studies, our hypothesis is that
the low grade inflammatory status found in the obese is related to a disrupted
intestinal integrity, leading to translocation of pro-inflammatory bacterial
compounds.

We want to study intestinal permeability and intestinal microbiota of obese and
people with normal weight in order to correlate these findings to various
parameters for inflammation and glucose homeostasis in the plasma.

We want to evaluate the relation between intestinal integrity and the
constitution of the intestinal microbiota, versus inflammatory and insulin
resistance in patients with morbid obesity and patients with a normal weight.

Interested patients will be instructed in outpatient clinic, and if they want
to participate in this project , a venous blood sample will be collected. Then
a second appointment will be made for the participant to undergo an intestinal
permeability testing procedure in outpatient clinic, implying a suger drink
followed by 5 hour urine collection. This morning, participant will bring a
faeces collector which is provided in advance.

Risk of test substance
The saccharide soluation consists of several sugars that are approved by the
Europese Union. These sugars have previously been used for researchpurposes and
it is not to be expected that they will have unintended side-effects. The risk
of drinking these sugars is very low.

The non steroid anti inflammatory drug that is used in the intestinal
permeability testing is a commonly used pain killer (in both the obese and
healthy control population) that is freely available in drug stores without
prescription, for pain for example in joints, fever, flu or cold, arthritis,
non-bacterial infections, oedema and dysmenorroea. In daily practice, this
NSAID (ibuprofen) is also used for headaches.

The side effects of this NSAID are in general relatively mild and mostly
invollve gastro intestinal discomfort . Most common side-effects are nausea,
anorexia, vomiting, diarrhoea, constipation, ulcus pepticum (with or without
bleeding or perforation). Central effects like migraine, headaches, dizziness,
exhaustion, confusion and tinnitus are possible. Exceptionally allergic
reactions take place, such as skin conditions (rask, exanthema, urticaria,
pruritus). In the dosage suggested for this protocol of 400 mg these side
effects are exceptional and therefor the risk is low.

Risk of procedures during the course of the study
The vanous blood sample is taken from the cubital vene in the arm, using a
classical method. This can be uncomfortable and if the vein is not hit
correctly, there could possibly rise a hematoma. This is however a very common
and routinely performed procedure and possible risk of an hematoma is very low
and will be explained to each participant in advance. In case of an hematoma,
it will resolve within days.