Bovine Milk Oligosaccharide Study

Study Overview
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Brief Summary
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The purpose of this study is to elucidate tolerability and effectiveness in consumption of the complex indigestible sugars from dairy products called bovine milk oligosaccharides (BMO) to enrich intestinal microflora toward beneficial populations.

Detailed Description
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This is a single-blind crossover study designed to determine if BMO at two different doses selectively enrich beneficial bacteria in the human gut and will be tolerated in healthy participants compared with a placebo control supplement. Each participant will consume two sachets of supplement for eleven days, separated by a two-week washout before starting the second and third arms. To determine the effect of dose, the placebo-control supplement will be administered in the first arm, followed by the low and high dose. Participants will collect stool and first morning urine and study personnel collected blood from each participant at baseline (day 0) and at the end (Day 11) of each study arm for all three arms.

Official Title
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Pilot Study: Tolerability of Feeding Different Doses of Bovine Milk Oligosaccharides for Modifying Gastrointestinal Function in Healthy Individuals

Conditions
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Healthy

Intervention / Treatment
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* Dietary Supplement: Bovine Milk Oligosaccharide
* Dietary Supplement: Placebo Glucose Polymer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men and women aged 18-40 years old BMI 18-25 Born by vaginal birth (not C-section) Breastfed for a minimum of 2 months after birth Exclusion Criteria: Individuals who regularly consume high fiber cereals or fiber supplements Individuals who frequently consume yogurt (eligible if willing to refrain consumption during the study period) Individuals who are lactose intolerant and/or allergic to dairy or wheat Individuals who use tobacco products Individuals who are pregnant or lactating Individuals with a known presence of gastrointestinal/malabsorption disorders or autoimmune disease Individuals taking prescription or over-the-counter medications that include pre/probiotics, corticosteroids, anti-obesity agents, laxatives, and lipid- altering medications

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Control, Glucose polymer<br>Treatment 1: Polycose Glucose Polymer Module powder (Abbott Nutrition, Abbott Park, Illinois 60064), fed as 25% of each individual's daily fiber intake based on calculated energy expenditure (14 grams of fiber for every 1000 kcal consumed) for eleven consecutive days. | Dietary Supplement: Placebo Glucose Polymer<br> <br> |
| Experimental: Treatment 2: Low-Dose BMO<br>Treatment 2: Bovine Milk Oligosaccharide (BMO) powder (Hilmar Ingredients, Hilmar, California 95324) Dosage: 25% of individual daily fiber intake, split into two daily servings Frequency: Two servings per day (for total of 25% dosage per day) Duration: 11 days, followed by a 2-week wash-out period Fiber intake was 25% of each individual's daily fiber intake based on calculated energy expenditure (14 grams of fiber for every 1000 kcal consumed) for eleven consecutive days. | Dietary Supplement: Bovine Milk Oligosaccharide<br>* The BMO powder will be isolated from whey streams by Hilmar Ingredients (Hilmar, California 95324). Hilmar Ingredients employs the same membrane filtration, and centrifugation processes used to purify whey protein in their commercial practice to extract and purify BMO from whey permeate. Furthermore, the same sterilization processes used on the equipment to purify whey products will be used to purify BMO. This method uses a novel high-throughput food-grade isolation protocol that leads to purification of specific BMOs with bifidogenic activity as prebiotic oligosaccharides that mimic the activities observed for Human Milk Oligosaccharides (HMO). This strategy of developing methods for their large scale fractionation allows us to obtain a final product that mimics the naturally beneficial oligosaccharides present in human milk.<br>|
| Experimental: Treatment 3: High-Dose BMO<br>Treatment 3: Bovine Milk Oligosaccharide (BMO) powder (Hilmar Ingredients, Hilmar, California 95324) Dosage: 35% of individual daily fiber intake, split into two daily servings Frequency: Two servings per day (for total of 25% dosage per day) Duration: 11 days, followed by a 2-week wash-out period Fiber intake was 35% of each individual's daily fiber intake based on calculated energy expenditure (14 grams of fiber for every 1000 kcal consumed) for eleven consecutive days. | Dietary Supplement: Bovine Milk Oligosaccharide<br>* The BMO powder will be isolated from whey streams by Hilmar Ingredients (Hilmar, California 95324). Hilmar Ingredients employs the same membrane filtration, and centrifugation processes used to purify whey protein in their commercial practice to extract and purify BMO from whey permeate. Furthermore, the same sterilization processes used on the equipment to purify whey products will be used to purify BMO. This method uses a novel high-throughput food-grade isolation protocol that leads to purification of specific BMOs with bifidogenic activity as prebiotic oligosaccharides that mimic the activities observed for Human Milk Oligosaccharides (HMO). This strategy of developing methods for their large scale fractionation allows us to obtain a final product that mimics the naturally beneficial oligosaccharides present in human milk.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut microbiota | Gut microbiota will be analyzed for 16s rRNA by next generation sequencing, terminal restriction fragment length polymorphism, and quantitative polymerase chain reaction. | Change from baseline to day 11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Metabolites | First morning urine samples will be analyzed by nuclear magnetic resonance spectroscopy. | Days 0, 4, 11 | 
| Plasma Lipid Profile | Fasting plasma lipid profile (total triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol) will be analyzed by enzymatic analysis by UC Davis Pathology Lab. | Day 0 and Day 11 | 
| Plasma Glucose | Fasting plasma glucose will be measured by enzyme analysis by UC Davis Pathology Lab. | Day 0 and Day 11 | 
| Dietary Macronutrient Intake | Participants will fill out three-day diet records for two weekdays and one weekend before starting each dietary supplemental arm in order to determine if intake of BMO vs. placebo control influences habitual dietary intake. | Day 0 | 
| Gut Tolerability | Participants will fill out a standardized gut tolerability questionnaire (Pedersen et al., 1997) rating their symptoms of gut and stomach discomfort on a 0-10 discretized visual analog scale daily seven days before starting each arm and on five different occasions on Days 0-10 during each study arm. | Days Minus 7 and Days 0-10 | 
| Stool Consistency | Participants will fill out the Bristol Stool Scale when they have bowel movements seven days before starting each study arm and daily during each study arm. The discretized visual analog scale 1-7 describes hardness to softness of stool. | Minus Day 7 and Days 0-10 | 
| Fecal BMO | Measurement of BMOs in feces | Days 0, 4 and 11 | 
| Fecal Metatranscriptome | Measurement of fecal metatranscriptome | Days 0 and 11 |