Probiotics as a Novel Approach to Modulate Gut Hormone Secretion and Risk Factors of Type 2 Diabetes and Complications

Study Overview
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Brief Summary
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The investigators aim to test the hypothesis that Lactobacillus Reuteri-enriched microbiota improves insulin sensitivity and glucose tolerance in obese healthy and obese type 2 diabetes patients by improving gut hormone secretion and compare these findings to healthy lean subjects.

Detailed Description
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Prediabetes and diabetes are accompanied by insufficient gut hormone release, insulin resistance, insufficient insulin secretory capacity and low grade systemic inflammation. Results of recent animal experiments suggest that ingestion of probiotics not only influences gut microbiota composition and intestinal permeability but also secretion of GLP-2 as well as insulin resistance, components of metabolic syndrome and diabetes development. GLP-2 secretion has been suggested to be a key mediator of probiotic effects mediating decreased intestine permeability through binding to intestinal GLP2 receptor in animal studies. Insulinotropic GLP-1, which is reduced in patients with type 2 diabetes, has also been described to be influenced by gut microbiota composition. We aim to test the hypothesis that Lactobacillus Reuteri-enriched microbiota improves insulin sensitivity and glucose tolerance in obese healthy and obese type 2 diabetes patients by improving gut hormone secretion. In a prospective, double-blinded, placebo controlled randomized 10 weeks trial we aim to investigate metabolic and immunological changes related to modified gut microbiota by analysing (1) gut hormone secretion, (2) insulin sensitivity and glucose tolerance, and (3) systemic LPS concentrations and immune status.

Official Title
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Phase I Study of Probiotics as a Novel Approach to Modulate Gut Hormone Secretion and Risk Factors of Type 2 Diabetes and Complications

Conditions
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Obesity, Type 2 Diabetes

Intervention / Treatment
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* Dietary Supplement: Lactobacillus reuteri


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Obese subjects: age 40 - 65 years, obesity (BMI 30-45 kg/m2), non-smoking, absence of gastrointestinal disease, willingness to abstain from intake of fermented milk products over a study period of 8 weeks. Healthy control subjects: non-obese (BMI 19-25 kg/m2), non-diabetic subjects, matched for age and sex, non-smoking, absence of gastrointestinal disease, willingness to abstain from intake of fermented milk products over a study period of 8 weeks. Exclusion Criteria: pregnancy, cancer, chronic diseases, antibiotic therapy, competitive athletes.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic capsule<br> | Dietary Supplement: Lactobacillus reuteri<br>* twice daily<br>|
| Placebo Comparator: placebo capsule<br> | Dietary Supplement: Lactobacillus reuteri<br>* twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin resistance |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| gut hormones (GLP-1, GLP-2, GIP) |  | 8 and 10 weeks | 
| insulin secretion |  | 8 and 10 weeks | 
| measurement of cytokines to define the immune status | measurement and analysis of proinflammatory cytokines (Interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1ß, Macropahge inflammatory protein (MIP)-1ß) and regulatory cytokines (IL-10, transforming growth factor (TGF)-ß, IL1ra) from peripheral blood samples collected during this trial | 8 and 10 weeks | 
| body weight |  | 8 and 10 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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probiotics, prevention, dietary intervention, insulin resistance, obesity, type 2 diabetes