Dissecting Host-microbiome Modifiers of Type 2 Diabetes Risk

Study Overview
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Brief Summary
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It is now well documented that changes in gut microbiota composition accompany obesity and type 2 diabetes (T2D) and contribute to low-grade inflammation, insulin resistance,and glucose intolerance. It is not yet clear if T2D predisposes the intestine to allow more microbial products or possibly live bacteria to subvert the gut mucosal barrier. However, it is known that hyperglycemia during T2D induces a more permissive gut barrier allowing increased penetration of microbes and their products into the blood. An important next step is to determine which strains of bacteria promote dysbiosis, allowing bacteria or bacterial components to subvert the gut barrier and alter glucose control. It is hypothesized that gut microbes in the colon and other lower gut segments are key modulators of energy balance, glucose homeostasis and insulin sensitivity.

Detailed Description
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The gut acts as a barrier to bacteria and nutrients and participates in glucose homeostasis via endocrine actors and the gut-brain-peripheral axis. It is unclear how T2D alters microbes in upper and lower intestine of humans. Studies in animals show that T2D promotes translocation of microbes to the blood and tissues to promote metabolic dysfunction. It is crucial to determine whether bacteria or their components subvert the gut barrier in human T2D, and then to identity the relevant bacterial strains in tissues that control blood glucose. The overall objective of our research program is to demonstrate that specific microbes in the gut, circulation, and key metabolic tissues are involved in the progression of T2D. We will define the microbial signatures of T2D in duodenal biopsies and stool samples by comparing T2D and non-T2D subjects.

Official Title
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Dissecting Host-microbiome Modifiers of Type 2 Diabetes Risk

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Procedure: Endoscopy and duodenal biopsy and sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: T2DB de novo or non T2DB patients Exclusion Criteria: oral hypoglycemic agents or lipidlowering or antihypertensive drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Type 2 Diabetes patients<br>Upper gut biopsies and lower gut samples | Procedure: Endoscopy and duodenal biopsy and sampling<br>* All volunteers will have endoscopy and duodenal biopsy and will have to provide stool samples<br>|
| Active Comparator: Non Type 2 Diabetes patients<br>Upper gut biopsies and lower gut samples | Procedure: Endoscopy and duodenal biopsy and sampling<br>* All volunteers will have endoscopy and duodenal biopsy and will have to provide stool samples<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbial signature | Compare the bacterial profile of T2D and non-T2D subjects | One week |