Walnut Consumption and Gut Microbiota

The Microbial and Metabolic Impact of Walnut Consumption in Adults With Obesity

Obesity is a growing health issue that effects the majority of adults in the United States. Prevalence of other metabolic diseases are increased in obese adults, including systemic inflammation. There is emerging evidence that the gut microbiota have a mediating role in controlling inflammation by producing butyrate when ingested fiber is fermented. Since these microbes are modifiable by diet, the investigators plan to introduce walnuts to the diets of participants with obesity because they are rich in fiber and unsaturated fatty acids. The purpose of this study is to understand the impacts of walnut consumption on the gut microbiota and the effect they have on bile acid profiles and systemic inflammation. The investigators intention is to identify how these walnut-derived molecules influence Faecalibacterium spp., a butyrate producing microbe. Increased levels of butyrate have shown to decrease secondary bile acids and decrease inflammation.

Study Overview

• Status: Active, not recruiting
• Conditions: Inflammation; Obesity
• Intervention / Treatment: Other: Walnuts; Other: Walnut Oil; Other: Control

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Urbana, Illinois, United States, 61801
      • Hannah Holscher

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Participants will include adults ages 25-75 years BMI of > 30 kg/m2 Ability to drop-off fecal sample within 15 minutes of defecation

Exclusion Criteria:

• Walnut allergy or intolerance
• Food allergies or intolerances
• Prior diagnosis of metabolic or gastrointestinal disease (cardiovascular disease and type 1 or type 2 diabetes, chronic constipation, diarrhea, Crohn's disease, celiac disease, ulcerative colitis, irritable bowel syndrome, diverticulosis, stomach or duodenal ulcers, hepatitis, HIV, cancer, etc.)
• Women that are pregnant, had a baby within the last 12 months, or lactating
• Individuals that smoke, use tobacco, abuse drugs, or consume > 2 alcoholic beverages per day.
• > 5% weight change in the past month or > 10% change in the past year
• Oral antibiotics during the previous 6 weeks
• Fasting blood glucose >126 mg/dL, blood pressure >160/100 mm Hg, elevation in serum transaminases (i.e. >3 times the upper limit of normal) or with evidence of liver disease, including primary biliary cirrhosis or gallbladder disease, constipation, are currently taking lipid-lowering medications, oral hypoglycemic agents, or insulin, or certain medications (laxatives, bile acid sequestrants, and opiates)
• History of malabsorptive or restrictive bariatric surgeries (e.g., gastric bypass, sleeve gastrectomy, adjustable gastric band) or gall bladder removal surgery.
• Are unable to consume the experimental meals/snacks.
• Participants who have donated blood within the last 8 weeks
• Recent diagnosis of anemia
• Concurrent enrollment in another dietary, exercise, or medication study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention treatment; Intervention treatment will contain walnuts and be consumed everyday for 3 weeks.	Other: Walnuts; The intervention treatment will contain walnuts.
Experimental: Intervention treatment oil; Intervention treatment will contain walnut oil in foods and be consumed everyday for 3 weeks.	Other: Walnut Oil; The intervention treatment will contain walnut oil.
Placebo Comparator: Control treatment; Intervention treatment will contain corn oil in foods and be consumed everyday for 3 weeks.	Other: Control; The control treatment will contain corn oil.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fecal Microbial Species	Abundances of fecal Faecalibacterium spp. and Roseburia spp measured using metagenomic sequencing in walnut and walnut oil vs. control.	Fecal samples will be collected at the end of each 3 week condition.
Concentration of fecal bile acids	Fecal bile acid concentrations measured using HPLC in walnut and walnut oil vs. control	Fecal samples will be collected at the end of each 3 week condition.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fecal Microbial Metabolites	Concentrations of fecal microbial metabolite (phenol/indoles, short chain fatty acids, and ammonia) concentrations measured using GC-MS in walnut and walnut oil in comparison to a control (corn oil)	Fecal samples will be collected once at the end of each 3 week condition.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fecal Microbiome	Relative abundance of microbial genes and genera measured using metagenomic sequencing of extracted fecal DNA to compare abundances between walnut, walnut oil, and corn oil.	Fecal samples will be collected at the end of each 3 week condition.
Inflammatory markers	LPS-binding protein and inflammatory markers (CRP and TNFa) concentrations in walnut and walnut oil vs. control (corn oil)	Blood samples will be collected at the end of each 3 week condition.
Serum bile acid profiles	Serum bile acid concentrations will be measured using LC-ESI-MS/MS to compare concentrations between walnut and walnut oil and control (corn oil)	Blood samples will be collected during a mixed-meal tolerance test that occurs at the end of each 3 week condition.
Mixed-meal tolerance test	Blood glucose and insulin concentrations and area under the curve will be measured in blood during a mixed meal tolerance test that includes a standard glucose beverage and the respective walnut, walnut oil, or corn oil treatment.	At the end of each 3 week condition.
Intestinal permeability	Intestinal permeability will be measured using a orally ingested sugar substitutes. 24-hour urinary appearance of the sugars will be quantified using GC-MS.	24-hour urine collections will occur at the end of each 3 week condition

Collaborators and Investigators

• Sponsor: University of Illinois at Urbana-Champaign

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Estimated): August 1, 2023
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: May 6, 2021
• First Submitted That Met QC Criteria: June 28, 2022
• First Posted (Actual): July 1, 2022

Study Record Updates

• Last Update Posted (Estimated): June 19, 2023
• Last Update Submitted That Met QC Criteria: June 15, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: inflammation; glycemia; Walnuts; gastrointestinal microbiota; bile acid profiles; insulinemia
• Additional Relevant MeSH Terms: Pathologic Processes; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Inflammation
• Other Study ID Numbers: 20164

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No