Epithelial barrier in obesity

Obesity is an increasing problem in the Western world. Obese subjects show
reduced satiety after food intake compared to lean subjects.
In obesity a low inflammory tone is measured, contributing to the development
of cardiovascular disease and the metabolic syndrome (hypertension,
hypercholesterolemia, insulin resistance etc.). In obese mice the gut
permeability is increased resulting of leakage of endotoxins. This further
contributes to inflammation. The gut microbiota may mediate this process. The
gut microbiota in obese mice extracts more efficiently the nutrients from the
food ingested. This has not yet been investigated in obese human subjects.

Gut permeability is likely to be increased in obesity, however, only small
studies have been performed in obese human subjects. Gut microbiota in obesity
is altered. The microbiota found in obesity is more efficient in extracting
energy from nutrients in the gut. After bariatric surgery significant weight
loss will occur. After surgery insulin resistance is reduced, cholesterol
levels and blood pressure decline.

Either the weight loss or the metabolic changes or both will lead to altered
gut microbiota probably supporting weight loss. Small bowel anatomy is
unaffected after sleeve gastrectomy. After sleeve gastrectomy tremendous weight
loss will occur, enabling us to investigate possible changes of gut microbiota,
gut permeability and inflammation due to weight loss and/or metabolic changes.

The aim of this study is to assess differences between lean and morbidly obese
subjects in gut permeability, gut microbiota and mucosal inflammation and to
assess the effects of weight loss after sleeve gastrectomy on gut permeability,
microbiota and mucosal inflammation over time.

The patient group is tested on 3 occasions:
- preoperatively
- 2 months after
- 6 months after

The control (lean) group is only tested during one occasion

Test day:
- 8.00 in the morning: patient reports at the
gastroenterology department
- 8.00-8.15: brief explanation of
the test, subjects are requested to empty their bladder in the toilet
- 8.15: breath sample is
taken, one blood sample is withdrawn (if not performed during routine blood
withdrawals)
- 8.15: sugar drink is
ingested, after ingestion of the sugar drink the patient collect the urine at
home.
- 8.15- 13.15: urine is collected in
first urine collector
- 8.15-13.15: only water may be
ingested
- 13.15 - 8.15 next day: urine is collected in second
urine collector (delivered to lab afterwards)
- 13.15-8.15: all diets are allowed
- stool samples can be collected at home and delivered at the laboratory
afterwards.-

Burden for each measurement
- drinking a sugar drink
- first five hours no other diet than water
- collecting urine during 24 hours
- collecting two stool samples
- collecting breath sample
- collecting blood sample (12 ml)

Obese subjects are investigated on 3 occassions, healthy control subjects on
one occassion.