Recruitment difficulty

New studies are revealing how a high-fat diet could be making the cells of the intestinal lining more likely to become cancerous. The investigators would like to study how obesity influences growth of intestinal stem cells, which could then trigger intestinal tumors.

The investigators are proposing a Pilot Study of 20 subjects (comprised of 10 participants from each of two different BMI categories: 20-25 and 35 & above), who will be asked to provide blood, stool, & urine samples, undergo a flexible sigmoidoscopy, and complete food frequency questionnaires

Hypothesis:

The investigators will test the hypothesis that the gut microbiome drives many of the effects that a pro-obesity high-fat diet has on intestinal stem cell (ISC) biology, which includes 1) an increase in ISC numbers and proliferation, 2) a reduced dependency on niche cells for intestinal organoid initiation, or 3) the acquisition of organoid-initiation by non-stem cell population in the intestinal epithelium.

Specific Aims:

1. To determine whether differences in the gut microbiome in obese human subjects correlates with enhanced intestinal stem cell numbers and function.
2. To validate whether obesity-driven changes in the gut microbiome of human recapitulate the effects of obesity on intestinal stem cell function in germ-free mice.

Subject and Control Inclusion Criteria

1. Participants have a Body Mass Index (BMI) between 20-25 or 35 and above.
2. Adults aged 18-65

Exclusion Criteria:

1. Known diagnosis of inflammatory bowel disease, microscopic colitis, celiac disease or other inflammatory conditions or diabetes mellitus
2. Antibiotic use within the past 4 weeks (they can be enrolled after a four week washout period and subsequent use during the 6 month study duration does not exclude them)
3. Bowel preparation for colonoscopy within the past week
4. Significant bowel surgery other than hysterectomy or appendectomy
5. Pregnancy or plans to become pregnant within the study time frame
6. Any other disease(s), condition(s) or habit(s) that would interfere with completion of study, or in the judgment of the investigator would potentially interfere with compliance to this study or would adversely affect study outcomes.
7. Age<18 or vulnerable adults -

Tissue samples will be sent to the Massachusetts Institute of Technology (MIT)