Interactions of Human Gut Microbiota With Intestinal Sweet Taste Receptors

Study Overview
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Brief Summary
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The purpose of this study is to collect data to examine whether short-term consumption of non-caloric artificial sweeteners (NCASs), such as saccharin, can lead to changes in blood sugar levels and in the composition of the bacteria in the large intestine.

Official Title
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Interactions of Human Gut Microbiota With Intestinal Sweet Taste Receptors

Conditions
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Obesity

Intervention / Treatment
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* Other: Oral Glucose Tolerance Test (OGTT)
* Other: Assessment of dietary compliance
* Other: Stool sampling
* Other: Sodium Saccharin
* Other: Placebo
* Other: Lactisole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide written informed consent Age 18-45 years Weight stable (± 3 kg) during the 6 months prior to enrollment BMI ≤ 25 kg/m2 Consumption of less than a can of diet beverage or a spoonful of NCASs weekly (or each equivalent from foods) during the past month Exclusion Criteria: Known coronary artery disease, angina or congestive heart failure Type 1 or Type 2 Diabetes (A1c ≥6.5%) Bleeding disorders Hemoglobin level < 12.5 g/dL for women; hemoglobin level < 13.0 g/dL for men Acute or chronic infections Hepatitis and/or cirrhosis Severe asthma or chronic obstructive pulmonary disease Renal insufficiency or nephritis (creatinine > 1.6 mg/dl) Prior bariatric surgery Inflammatory bowel disease or malabsorption Cancer within the last 3 years (except non-melanoma skin cancer or treated cervical carcinoma in situ) Psychiatric disorders or eating disorders Cushing's disease or syndrome Untreated or inadequately controlled hypo- or hyperthyroidism (abnormal TSH) Active rheumatoid arthritis or other inflammatory rheumatic disorder Pregnant or nursing women Smoking (smoking within the past 3 months) Less than 4 bowel movements per week Known hypersensitivity to saccharin, lactisole or any of its excipients. Excluded medications include but are not limited to: Anti-diabetic agents Oral, injected or chronic topical steroids (inhaled steroids for mild asthma are acceptable) Antibiotic use (within the past 3 months) Other drugs known to affect immune or metabolic function Orlistat, phentermine, topiramate or other weight loss or anorectic agents (tricyclic antidepressants, atypical antipsychotics or other psychiatric drugs with effects on body weight)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1- Healthy Lean subjects<br>Group 1 will receive Sodium Saccharin 200mg capsule, 2x/day, Day 1-14 | Other: Oral Glucose Tolerance Test (OGTT)<br>* Once we test the fasting plasma glucose (after an overnight fast), subject will receive a 75g glucose beverage they will have to drink within 5 minutes. Then after drinking the beverage, 8 blood samples will be collected through the IV catheter, over the next 3 hours.<br>Other: Assessment of dietary compliance<br>* Assessment of consumption of non-caloric artificial sweeteners<br>Other: Stool sampling<br>* Subjects will provide a stool sample.<br>Other: Sodium Saccharin<br>* Subjects in group 1 and group 3 will be provided with sodium saccharin.<br>|
| Active Comparator: Group 2- Healthy Lean subjects<br>Group 2 will receive Placebo 500mg capsule, 2x/day, Day 1-14 | Other: Oral Glucose Tolerance Test (OGTT)<br>* Once we test the fasting plasma glucose (after an overnight fast), subject will receive a 75g glucose beverage they will have to drink within 5 minutes. Then after drinking the beverage, 8 blood samples will be collected through the IV catheter, over the next 3 hours.<br>Other: Assessment of dietary compliance<br>* Assessment of consumption of non-caloric artificial sweeteners<br>Other: Stool sampling<br>* Subjects will provide a stool sample.<br>Other: Placebo<br>* Subjects in group 2 will be provided with placebo.<br>|
| Active Comparator: Group 3- Healthy Lean subjects<br>Group 3 will receive Sodium Saccharin 200mg + lactisole 335mg capsule, 2x/day, Day 1-14 | Other: Oral Glucose Tolerance Test (OGTT)<br>* Once we test the fasting plasma glucose (after an overnight fast), subject will receive a 75g glucose beverage they will have to drink within 5 minutes. Then after drinking the beverage, 8 blood samples will be collected through the IV catheter, over the next 3 hours.<br>Other: Assessment of dietary compliance<br>* Assessment of consumption of non-caloric artificial sweeteners<br>Other: Stool sampling<br>* Subjects will provide a stool sample.<br>Other: Sodium Saccharin<br>* Subjects in group 1 and group 3 will be provided with sodium saccharin.<br>Other: Lactisole<br>* Subjects in group 3 and group 4 will be provided with lactisole.<br>|
| Active Comparator: Group 4- Healthy Lean subjects<br>Group 4 will receive Lactisole 335mg capsule, 2x/day, Day 1-14 | Other: Oral Glucose Tolerance Test (OGTT)<br>* Once we test the fasting plasma glucose (after an overnight fast), subject will receive a 75g glucose beverage they will have to drink within 5 minutes. Then after drinking the beverage, 8 blood samples will be collected through the IV catheter, over the next 3 hours.<br>Other: Assessment of dietary compliance<br>* Assessment of consumption of non-caloric artificial sweeteners<br>Other: Stool sampling<br>* Subjects will provide a stool sample.<br>Other: Lactisole<br>* Subjects in group 3 and group 4 will be provided with lactisole.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood analyzed by way of NOVA StatStrip Meter and Milliplex Map Kit. |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short chain fatty acid analyses | Stool sample aliquoted and frozen by way of ribosomal sequencing, which will be used to determine what bacteria is in the fecal sample. | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucose, Sweet taste receptors, Artificial sweeteners