Impact of Blueberry Consumption on Gastrointestinal Health

Study Overview
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Brief Summary
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This study will evaluate the impact of blueberry consumption on markers of gastrointestinal health including gut microbiota, intestinal permeability, and gut-derived inflammation in those vulnerable to a unhealthy gut milieu. All participants will consume a blueberry powder and a placebo in this crossover study.

Detailed Description
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The commensal bacteria that reside in the human gut, known as the gut microbiota, is a complex system that modulates local gut homeostasis and systemic biological processes. Several environmental factors have been shown to influence the gut milieu (including microbiota), and thus both gastrointestinal and host health. Relevant to the current proposal is the influence of body weight, diet, and circadian rhythms. In the current study, the investigators propose to use these common disruptors of gastrointestinal health through recruiting obese shift workers with a low-fiber diet to identify if these disrupted individuals can benefit from blueberry intake. Specifically, the study objectives are to determine if 24 g whole blueberry powder consumed daily can beneficially modify intestinal permeability, gut microbiota, microbial metabolites, and both gut-derived and systemic inflammation in those most susceptible to a pro-inflammatory milieu. This will be accomplished through a 14-week crossover study in which 28 individuals will be randomized by treatment group order to 4 weeks of whole blueberry powder and placebo powder, with a 4-week wash out in between the treatment periods.

Official Title
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Impact of Blueberry Consumption on Intestinal Permeability, Gut Microbiota, and Gut-Derived Inflammation in Individuals With Elevated Risk of a Pro-Inflammatory Gut Milieu

Conditions
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Obesity, Circadian Dysregulation

Intervention / Treatment
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* Dietary Supplement: Blueberry powder
* Dietary Supplement: Placebo powder


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: obese (BMI +/- 30.0 kg/m2) shift workers (shift work overnight (third shift) +/= 3 days/week for the past 3 months) 19-70 years of age Exclusion Criteria: patient history of gastrointestinal diseases except for hiatal hernia, GERD, or hemorrhoids, mild gastrointestinal symptoms elevated laboratory values from a comprehensive metabolic panel (CMP) and complete blood count (CBC) with the exception of glucose (+/= 126 mg/dL; if elevated, confirmed with HA1c of greater than or equal to 6.5%) and ALT, AST, or ALP over 2 times normal levels (to allow for mild elevations resulting from fatty liver often seen in obese) unless approved by study physician currently pregnant or plans to become pregnant during the study as determined by participant report antibiotic use within the last 12 weeks prior to enrollment presence of chronic metabolic disease (e.g., cardiovascular disease, diabetes, cancer) or per physician discretion recent (past 4 weeks) major change in dietary habits or a plan to have a major change in dietary habits during the study habitual blueberry consumption of more than 0.5 cups 2x/week or a 4-week washout period if consumes allergy or intolerance to blueberries consumption of supplemental fiber, probiotics or prebiotics without an appropriate 4-week washout period restrictive dietary patterns (e.g., ketogenic, Paleolithic) or a diet high in fiber (+/= 14 g/1000 kilocalories) to increase study result generalizability to the U.S. population (low-fiber diet), as well as provide another stimuli for gut leakiness unwillingness to consent to the study.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 70 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: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This 14-week crossover study includes 4 weeks for each of the two supplementation periods (blueberries and placebo), with a 4-week wash out between.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blueberry powder<br>4 weeks of supplementation of 24 g whole blueberry powder | Dietary Supplement: Blueberry powder<br>* Dried, powdered blueberries will be consumed at 24 g/day in two divided doses at least 4 hours apart.<br>|
| Placebo Comparator: Placebo powder<br>4 weeks of supplementation of 24 g placebo powder (maltodextrin) | Dietary Supplement: Placebo powder<br>* A placebo consisting maltodextrin will be consumed at 24 g/day in two divided doses at least 4 hours apart.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| intestinal permeability | urinary sugar measurement by gas chromatography (GC): Sucralose, lactulose, mannitol, sucrose as a percent of oral dose. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiota | Microbiota composition through shotgun sequencing. Composition includes relative abundance of all microbes in stool. | 28 days | 
| Microbial metabolites | Quantity of stool short-chain fatty acid (butyrate, propionate, acetate) per dry stool weight by gas chromatography | 28 days | 
| Gut-derived/systemic inflammation | Concentration of serum lipopolysaccharide (LPS), LPS-binding protein (LBP), and interleukin-6 (IL6) | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blueberry, Microbiota, Intestinal permeability