Investigation of the Gut Microbiota in Regulating Nutrient Absorption in Humans
Condition: Obesity
MeSH terms: Obesity
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      The prevalence of obesity has risen to epidemic proportions in the world, resulting from both
      excessive energy intake and low levels of energy expenditure. The effect of nutrient
      absorption on energy balance, that is, the relative amount of nutrients consumed vs. the
      amount excreted in stool, has been reported only in small studies in which energy waste in
      feces and urine between lean and obese individuals was not found to be different. New studies
      have shown that bacteria in the gut may play an important role in calorie absorption. We have
      recently shown that leaner individuals absorbed more calories when overfed compared to when
      they were given a diet with just enough calories to maintain their own weight. Our studies
      have also found that overfeeding also changes the kinds of bacteria found in the gut. In lean
      individuals, these changes in gut bacterial communities with overfeeding were associated with
      changes in how many calories were absorbed. Our results are similar to those seen in other
      studies in animals and humans that suggest a role for gut bacteria in weight gain and
      obesity. To try to better understand the role of gut bacteria in absorbing food, we propose
      to investigate 1) whether energy loss (as measured in stool and urine) changes following
      over- and underfeeding relative to body size and 2) whether changes in the gut bacteria,
      induced by an antibiotic medication, affect nutrient absorption and glucose tolerance. We
      plan to study 24 healthy non-smoking volunteers age 18 45 years old, not taking any
      medications (including medications for weight loss, antibiotics or probiotics) for the
      examination. All participants will be admitted to the Clinical Research Unit for 31 days.
      During their stay, subjects will be fed a weight maintaining diet for 3 days, followed by two
      experimental diets (150% and 50% of weight maintaining calories) in a random order. After
      this, volunteers will be randomly assigned to one of two groups: group 1 will take oral
      antibiotic medication; group 2 will receive pills that look the same but will not contain any
      active medication (placebos). Feces (stool) will be collected throughout the study.
      Additionally, twenty four-hour urine collections will take place each day of the experimental
      diet period and when stool is collected on the antibiotics. The energy content of these waste
      products as well as that of the diet (using duplicate plate analysis) will be measured by
      bomb calorimetry. Bacterial components in feces will be extracted by repeated fractional
      centrifugation to obtain bacterial mass and by using 16S rDNA-based oligonucleotide probes to
      obtain data on gut bacteria. Primary results will examine how many calories remain in stool
      during relative over- and underfeeding and whether changes in gut bacteria, induced by an
      antibiotic medication, affect nutrient absorption and glucose tolerance.
    

Intervention name(s): Vancomycin; Placebo oral tablet; Overfeeding diet (OF); Underfeeding diet (UF)
Intervention type(s): Drug; Drug; Other; Other
Intervention description(s): 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
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Gut Microbiota; Obesity; Absorption; Overfeeding