Defining the Role of the Gut Microbiome in Mediating the Effects of Obesity on Intestinal Stem Cells

Not Applicable

Terminated

• Conditions: Obesity
• Interventions: Procedure: Flexible Sigmoidoscopy

• Registration Number: NCT02863029
• Lead Sponsor: Mayo Clinic

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study First Submitted: 2016-08-03
• Study First Submitted QC: 2016-08-08
• Study First Posted: 2016-08-11
• Study Start: 2017-01
• Primary Completion: 2017-03-09
• Study Completion: 2017-03-09
• Status Verified: 2022-02
• Last Update Submitted: 2022-02-17
• Last Update Posted: 2022-02-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 4

Inclusion Criteria

Not provided

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 -

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Flexible Sigmoidoscopy	Flexible Sigmoidoscopy	Participants will undergo an unsedated Flexible Sigmoidoscopy in order to obtain 12 mucosal biopsies. Serum cholesterol, triglyceride and HBA1C levels will be determined. Plasma, serum and whole blood will be stored for future use for next generation sequencing and metabolomics to determine the effect of different genetic loci on composition and function of gut microbiota

Primary Outcome Measures

Name	Time	Method
Changes in the growth of intestinal stem cells	Two years	The gut microbiome is altered in obesity and studying intestinal stem cells will be helpful in learning what triggers intestinal tumors.

Trial Locations

Locations (1)

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States