Investigation of the Gut Microbiota in Regulating Nutrient Absorption in Humans

• INCLUSION CRITERIA:

Free of acute and chronic diseases (especially GI disorders) as determined by medical history, physical examination and laboratory tests.

Individuals may be taking laxative drugs but they must be discontinued 3 or more weeks before admission.

Age 18-45 y (in order to minimize the affect of aging on nutrient absorption).

EXCLUSION CRITERIA

Because it is unclear how chronic illnesses or substance abuse could affect nutrient absorption we will exclude volunteers with chronic diseases or current substance abuse. This is especially important because the limited number of study subjects in this study will make it hard to control for these confounders. We will therefore exclude subjects with a history or clinical manifestation of:

• Current smoking
• Type 2 diabetes (according to the World Health Organization diagnostic criteria)
• Endocrine disorders, such as Cushing s disease, pituitary disorders, and hypo- and hyperthyroidism
• HIV infection (self-report), due to effects on weight and body composition of HIV and medications used to treat HIV
• Active tuberculosis (self-report)
• Asthma on active daily treatment with medications
• Pulmonary disorders including physician diagnosed chronic obstructive pulmonary diseases and obstructive sleep apnea syndrome
• Cardiovascular diseases, including coronary heart disease, heart failure, arrhythmias, and peripheral artery disease
• Hypertension (according to the World Health Organization diagnostic criteria), treated or uncontrolled
• Gastrointestinal disease, including inflammatory bowel diseases (e.g. Crohn s disease and ulcerative colitis), malabsorption syndromes (e.g. celiac disease), gastric ulcer (active) and irritable bowel syndrome.
• Lactose intolerance
• Anemia (defined as hemoglobin < 11 mg/dl), leucopenia (defined as white blood cell count < 4,000/microL) or thrombocytopenia (defined as platelet count < 150,000/microL)
• Liver disease, including non-alcoholic fatty liver disease or current elevated liver enzymes over 1.5 times the normal range for AST, ALT or GGT or a history and physical exam that indicates a potential liver disease as describe by Giannini et al
• Evidence of chronic renal disease as defined by estimated glomerular filtration rate of < 60 ml/min or evidence of overt proteinuria on urine dipstick.
• Central nervous system disease, including previous history of cerebrovascular accidents, dementia, and neurodegenerative disorders
• Cancer requiring treatment in the past five years, except for non-melanoma skin cancers or cancers that have clearly been cured or in the opinion of the investigator carry an excellent prognosis
• Behavioral or psychiatric conditions that would be incompatible with a safe and successful participation in the study (such as major depression, schizophrenia and presence of psychotic symptoms)
• Eating disorders such as anorexia nervosa, bulimia or binge eating syndrome
• Taking weight loss drugs
• Weight change of more than 5% of total body weight in the 3 months before admission
• Use of any antibiotic or probiotic agents within 6 months prior to minimize the potential effects of these substances on the gut microbiota.
• Use of antacids (Proton pump inhibitors, H2 antagonists or aluminum/magnesium hydroxide) 3 months prior to the study assessed by self-report because a modified gastric pH might affect the gut microbiota as well
• Evidence of alcohol and/or drug abuse (more than 3 drinks per day and use of drugs, such as amphetamines, cocaine, heroin, or marijuana)

The following exclusion criteria are necessary because of the substances given or tests performed during the study

• Known allergies to vancomycin
• Known allergies to heparin or a history of heparin-induced thrombocytopenia
• Personal history or evidence of a bleeding disorder

All individuals will be fully informed of the aim, nature, and risks of the study prior to giving written informed consent. The study s informed consent will be obtained by