Effect of Yakult Ingestion on Diet-induced Insulin Resistance in Humans

Study Overview
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Brief Summary
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Participants will be randomly allocated to either Yakult ingestion or a control group. For the first 20 days, subjects will consume their normal diet (keeping a detailed food diary throughout). On days 21-28 they will switch to a high-fat/high-calorie diet. The investigators hypothesise that consuming a high-fat, high-energy diet for 7 days will alter the composition of the gut microbiota and induce metabolic endotoxaemia / systemic inflammation as well as decreasing whole body insulin sensitivity (as we have shown previously). In contrast, the investigators hypothesise that consuming Yakult for 21 days before and 7 days throughout the high-fat diet will maintain a favourable gut microbiota and prevent metabolic endotoxaemia / systemic inflammation and thus maintain insulin action / insulin sensitivity.

Official Title
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Effect of Yakult Ingestion on Diet-induced Insulin Resistance in Humans. A Large-cohort, Mechanistic Follow-up Study.

Conditions
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Insulin Sensitivity, Insulin Resistance, Type 2 Diabetes Mellitus

Intervention / Treatment
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* Dietary Supplement: Yakult light


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females Aged 18-30 Physically active (exercising at least 3 times per week for more than 30 min at a time) Non-smoker Free from cardiovascular or metabolic disease Weight stable for at least 6 months Normal body mass index (BMI: 18.5-24.9 kg/m2)* Compliant (i.e. understands and is willing, able and likely to comply with all study requirements) Note: If BMI is >24.9, but body fat % (as measured by bioelectrical impedance analysis) is below 21% in males and 31% in females, then the subject may still be recruited at the PI's discretion. Exclusion Criteria: Using probiotic or prebiotic supplements within the previous 3 months Vegetarians and vegans Diagnosis of insulin resistance, pre-diabetes or full diabetes Underweight (determined as BMI less than 18.5 kg/m2) Overweight or obese (determined as BMI greater than 24.9 kg/m2) Those on a calorie controlled diet or other dietary restrictions that would prevent them from consuming the probiotic treatment and high fat/high calorie diet. Those who are unwilling to restrict their intake of fermented dairy products. Those with known or suspected food intolerances, allergies or hypersensitivity Women who are known to be pregnant or who are intending to become pregnant over the course of the study. Participation in another clinical trial Those who have donated blood within 3 months of the screening visit and participants for whom participation in this study would result in having donated more than 1500 ml of blood in the previous 12 months. Participants who take any form of regular medication that is known to affect either the gut microbiota and/or insulin sensitivity or who have taken any antibiotics in the previous 3 months. Participants who know they would not be available for all the lab visits during the 4-week study period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 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
Interventional Model Description: Open label, control trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>Participants will receive 2 x 65mL doses of Yakult light per day, for 28 days. Participants will consume a high-fat (65% of kilocalories) high-calorie (150% of requirements) diet from day 21 to day 28. | Dietary Supplement: Yakult light<br>* A fermented milk drink containing the probiotic Lactobacillus casei Shirota<br>|
| No Intervention: Control Group<br>Participants will consume a high-fat (65% of kilocalories) high-calorie (150% of requirements) diet from day 21 to day 28. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole body insulin sensitivity index | Assessed by oral glucose tolerance test. | The change between pre- and post-high fat diet (assessed on days 21 and 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Mass Index | Calculated from height and weight. | Day 0, Day 21 and Day 28 | 
| Fasting plasma glucose concentration | Measured in fasting plasma sample. | Day 0, Day 21 and Day 28 | 
| Fasting serum insulin concentration | Measured in fasting serum sample. | Day 0, Day 21 and Day 28 | 
| Fasting plasma triglyceride concentration | Measured in fasting plasma sample. | Day 0, Day 21 and Day 28 | 
| Metabolic endotoxaemia | Plasma markers of endotoxaemia | Day 0, Day 21 and Day 28 | 
| Markers of systemic inflammation | Selected plasma cytokines and chemokines | Day 0, Day 21 and Day 28 | 
| Incretin response to glucose ingestion | GLP-1 | Day 0, Day 21 and Day 28 | 
| Microbiome analysis | Faecal DNA analysis of the gut microbiota | Day 0, Day 21 and Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gut Microbiota, High Fat Diets, Probiotics, Glycaemic Control