Investigation of the Gut Microbiota in Regulating Nutrient Absorption in Humans
Condition: Obesity
MeSH terms: Obesity
Intervention: Vancomycin; Placebo oral tablet; Overfeeding diet (OF); Underfeeding diet (UF)
Intervention description: Vancomycin 125mg orally four times per day for 12 days; Placebo pills orally four times per day for 12 days; Diet in which the calories are 150% of their weight maintaining energy requirements; Diet in which the calories are 50% of their weight maintaining energy requirements
Intervention MeSH terms: Vancomycin
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: Gut Microbiota; Obesity; Absorption; Overfeeding

Summary:

      We propose to study both stool and urine energy loss in 24 individuals on two experimental
      diets (50% increased and 50% reduced nutrient load relative to body size) in a random
      cross-over design. Following this over/underfeeding, volunteers will also be randomly
      assigned to a placebo versus oral antibiotic medication arm. This study will extend our
      previous findings by investigating whether 1) nutrient absorption changes upon similar
      increases/decreases in relative nutrient load and 2) whether manipulation of gut microbial
      communities with antibiotics alters nutrient absorption and 3) how these changes may affect
      glucose tolerance and fat storage.
    

Eligibility criteria:

        -  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 a
        principal or associate investigator, research physician or physician assistant working in
        the clinical research unit.