Investigating the Effect of Fermented Whey Concentrate on Gut Microbial Activity: Does Butyrate Matter?
Trial Snapshot
- Phase
- Not Applicable
- Status
- Terminated
- Sponsor
- University of Aberdeen
- Enrollment
- 43
- Locations
- 2
- Primary Endpoint
- Faecal butyrate concentration - comparing upper and lower tertile of volunteers
Study Overview
Brief Summary
This 8-week intervention will investigate the effect of daily consumption of a fermented whey concentrate on the short-chain fatty acid profile of faeces in healthy individuals.
This study will help us understand if consumption of fermented foods rich in lactic acid have a beneficial effect on gut health.
Detailed Description
The 8-week dietary supplementation trial will investigate the action of exogenous lactic acid consumption on the activity (using short-chain fatty acid) and composition of the gut microbiota.
Participants will be stratified according to their baseline faecal butyrate levels. Therefore volunteers will be asked to provide two faecal samples one week apart. Based on the average absolute level of butyrate in the faecal samples, volunteers will be stratified into either low, moderate or high baseline butyrate levels (detailed in table 1 below). The levels for faecal butyrate for each group are set based on a meta-analysis of 9 human studies of healthy volunteers carried out at the Rowett Institute (n=116; LaBouyer et al, 2016, unpublished). Thresholds were derived from the boundaries of tertiles. Therefore, the moderate butyrate producers represent the middle 33% (see table). Each stratification arm will have a minimum of 17 study volunteers bringing the total to n=51. This has been set to ensure the completion of at least 45 volunteers. To optimise equal gender distribution amongst all study arms a minimum of 5 females and 5 males will be recruited for each arm.
Stratification Butyrate range Low ≤13 mM Moderate butyrate 13 - 20mM High butyrate ≥20mM
Primary and secondary outcomes will be analysed between the low and high butyrate producing groups as well as the overall group effect on everyone.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Other
- Masking
- None
Masking Description
The intervention will be provided in non-descript bottles. Fermented whey is mixed with sugar-free flavoured water to mask its taste from participants.
Eligibility Criteria
- Ages
- 18 Years to 68 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •i. Men and women aged 18-68 years; BMI ranging from 18-35 kg/m2; measured at the screening visit
Exclusion Criteria
- •i. smokers
- •ii. subjects with: diagnosis of diabetes, pregnant, hypertension, renal, hepatic, haematological disease, coronary heart disease or any gastrointestinal disorder
- •ii. unsuitable veins for blood sampling;
- •iii. inability to speak, read and understand English.
- •iv. Use of antibiotics within the last 3 months will automatically exclude volunteers.
- •v. Vegans. Fermented whey concentrate, (FWC), is derived from milk (animal product) which excludes potential participants adhering to a vegan diet.
- •vi. allergy to any of the following: cow milk, lactose, casein, whey, sucralose, acesulfame K, citric acid, potassium benzoate, fruit flavourings.
Outcomes
Primary Outcomes
Faecal butyrate concentration - comparing upper and lower tertile of volunteers
Time Frame: Baseline measurement (Visit 1) and end of study (visit 3, 8 weeks later) [Baseline butyrate calculated from the average of two values per individual at Day -7 and Day 0; End of study value is the average from two samples collected at Day 49 and 56
Change in relative proportion of butyrate (percentage of total SCFA - sum of propionate, butyrate, acetate, valerate, iso-valerate, iso-butyrate, succinate, lactate mM (millimolar values from gas chromatography) and absolute concentration (mM millimolar) when comparing volunteers as stratified by faecal butyrate levels at start of study. A comparison will be made between the butyrate concentration-dependent groupings.
Faecal butyrate concentration - intervention group effect
Time Frame: Baseline measurement (Visit 1) and end of study (visit 3, 8 weeks later) [Baseline butyrate calculated from the average of two values per individual at Day -7 and Day 0; End of study value is the average from two samples collected at Day 49 and 56
Change in relative proportion of butyrate (percentage of total SCFA) and absolute concentration (mM, millimolar) across the total study group
Microbiota composition change
Time Frame: Assessed as change between day 0 and day 56
Changes in the composition of the microbiota will be based on next-generation sequence analysis of 16S rRNA (ribosomal ribonucleic acid) genes extracted from faecal samples provided by all volunteers
Secondary Outcomes
- Gastrointestinal wellness questionnaire(Day 0, 7, 14, 21, 28, 35, 42, 49 and 56)
- Glucose tolerance and insulin sensitivity(Measured on Day 0 and Day 56)
- Health related quality of life questionnaire(scored on Day 0 and 56)
- Small intestinal fermentation(measured on Days 0, 14 and 56)
- Faecal pH(measured at day 0 and 56)
- Faecal moisture content(measured at day 0 and 56)