Comparison of the Microbial Composition in Lean and Obese Subjects
Comparison of the Microbial Composition in Lean and Obese Subjects
Rationale: The microbial composition in the small intestine (SI) differs largely from the
 composition in feces. Many physiological processes related to health, such as
 immunoregulation and metabolic programming, mainly take place in the SI. Therefore, the SI,
 from a microbiota perspective, is as relevant as the large intestine. There are indications
 that microbiota composition is different in lean and obese subjects, and is related to
 insulin resistance. However, these indications are mainly based on the analysis of fecal
 samples. Therefore, analysis of the microbiota composition in the more proximal part of the
 gastrointestinal (GI) tract may provide new insights into the microbial species that are
 involved or related to metabolic homeostasis at that location. The IntelliCap® CR system
 offers a minimally invasive tool that is able to collect reliable samples in the SI, as was
 shown by NIZO in a clinical validation study. The main aim of the current study is to explore
 and compare the upper GI microbiota composition in lean and obese subjects, in order to
 generate new leads for development of products that may target the upper GI microbiota
 community or specific species thereof, which may impact the maintenance of metabolic
 homeostasis. This may provide new opportunities for the treatment, reduction or prevention of
 overweight and/or obesity or insulin resistance.
Inclusion Criteria:

 -  Female;

 -  Age: 25-50y;

 -  Lean: BMI 19-23 kg/m2, waist circumference <80 cm, and fasting glucose <6.1 mmol/L;
 Obese: BMI 30-35 kg/m2, waist circumference >88 cm, and fasting glucose >=6.1 and <7.5
 mmol/L;

 -  Healthy as assessed by the NIZO lifestyle and health questionnaire ("Verklaring
 leefgewoonten en gezondheid");

 -  Healthy as assessed by results of the pre-study safety laboratory tests (clinical
 chemistry: liver/kidney function etc);

 -  Regular and normal Dutch eating habits as assessed by the NIZO lifestyle and health
 questionnaire (3 main meals per day);

 -  Regular bowel movement (defecation on average once a day, at least 4 times/week).

 Exclusion Criteria:

 -  Participation in any clinical trial with oral, intravenous or inhalatory
 administration of any substances during 90 days before study start;

 -  History or presence of any clinically important disease or disorder which, in the
 opinion of the Investigator, may either put the subject at risk because of
 participation in the study, or influence the results or the subject's ability to
 participate in the study:

 -  type 1 or type 2 diabetes;

 -  gastrointestinal disease;

 -  bariatric surgery;

 -  cardiovascular disease, liver or renal failure or disease of the thyroid gland,
 cancer;

 -  infectious disease, history of chronic active inflammatory disorders or food
 allergy;

 -  Use of antibiotics during the one (1) year prior to study start; #

 -  Constipation/infrequent bowel movement (defecation <4 times per week);

 -  Having diarrhea within 3 months prior to the study start (at least 3 loose stools per
 day);

 -  Use of laxatives, fiber supplements (e.g. lactulose, inulin), glucose lowering drugs,
 insulin, anti-obesity drugs, immunosuppressive drugs (e.g. systemic corticosteroids,
 cyclosporine, azathioprine, antibodies) during the three (3) months prior to study
 start;

 -  Use of temporary or irregular medication for diabetes, dyslipidemia or hypertension;

 -  Use of any prescribed or non-prescribed medication (other than paracetamol) including
 antacids, H2 receptor antagonists, proton pump inhibitors, analgesics, herbal remedies
 or anti-inflammatory drugs (e.g. NSAIDs) during the three (3) weeks prior to study
 start;

 -  Use of probiotics or prebiotics during the three (3) months prior to study start;

 -  Mental status that is incompatible with the proper conduct of the study;

 -  Presence of swallowing or passage disorder;

 -  Carrying a pacemaker or any other (implanted) medical electronic device;

 -  Scheduled for an MRI scan during the study period;

 -  Not willing to have an X-ray if the capsule is not recovered from the faeces;

 -  Alcohol consumption > 15 units/week and >3/day. In case of less alcohol consumption:
 not willing to stop during the study;

 -  Drug abuse, and not willing/able to stop this during the study;

 -  Heavy exercise or sports training > 10 hours/week;

 -  Smoking;

 -  Active or recent participation in a weight loss program including weight change
 (increase or loss) of >3 kg during the last three (3) months;

 -  Reported unexplained weight loss or weight gain of > 5 kg in the year prior to
 pre-study screening;

 -  Reported slimming or medically prescribed diet;

 -  Reported special diets;

 -  Pregnant or planning to become pregnant during the study, breastfeeding ;

 -  Postmenopausal women on unstable hormone replacement therapy.