Gut, Immune, and Vascular Health in Metabolically Healthy Obesity

Impaired Gut-Vascular Axis as a Unique Driver of Cardiovascular Disease in Metabolically Healthy Obesity

The investigators seek to better understand how a single high-fat meal impacts gut, immune, and vascular outcomes in individuals with "metabolically healthy obesity" (obesity and largely normal cardiometabolic profile) and "metabolically healthy normal-weight individuals." Second, the investigators seek to understand how a prebiotic fiber (inulin) impacts gut, immune, and vascular outcomes in individuals with "metabolically healthy obesity."

Study Overview

• Status: Recruiting
• Conditions: Metabolically Healthy Obesity
• Intervention / Treatment: Dietary supplement: Inulin Supplementation; Dietary supplement: Maltodextrin (Placebo); Other: High-fat meal

Detailed Description

This study consists of two parts (part 1 and part 2) that are approved under the same IRB approval code. As a result, there is only one unique identifier for the entirety of this project. As a results, the investigators have included both parts in this registration.

Part 1 of project:

The investigators will recruit individuals with a BMI in the normal (18.5-24.9 kg/m2) or obesity (>30.0 kg/m2) ranges from the Ball State University campus and surrounding communities. At a screening visit, the investigators will measure metabolic syndrome risk (blood pressure, triglycerides, glucose, HDL-C) to see if individuals meet criteria for "metabolically healthy obesity" and "metabolically healthy normal-weight" - our two groups of interest.

Each participant will complete one meal trial. At the meal trial, an intravenous catheter will be inserted and baseline blood sample collected. Next, vascular assessments (i.e., flow mediated dilation [FMD], pulse wave analysis [PWA], pulse wave velocity [PWV]) will be completed. Then, participants will consume the high-fat meal consisting of heavy cream, chocolate syrup, and protein powder. The meal will contain ~700 calories (55g fat).

Following completion of the meal, blood samples will also be collected at 1-, 2-, 3-, 4-, 5-, and 6-hours. At each time point the investigators will collect serum to assess biomarkers of intestinal permeability and inflammation. Serum will also be used in mechanistic experiments where the investigators will treat endothelial cells in culture with serum from participants pre/post high-fat meal and examine differences in gene and protein expression, as well as nitric oxide production. Additional blood will be collected for peripheral blood mononuclear cell isolation at baseline and 3 hours. Vascular assessments listed above will be repeated at 2-, 4-, and 6-hours.

Participants will provide a stool sample collected at home for microbiome analyses.

Part 2 of project:

The investigators will recruit individuals with a BMI in the obesity (>30.0 kg/m2) range from the Ball State University campus and surrounding communities. At a screening visit, the investigators will measure metabolic syndrome risk (blood pressure, triglycerides, glucose, HDL-C) to see if individuals meet criteria for "metabolically healthy obesity" - our sole group of interest.

Qualifying participants will report for a baseline assessment. At the baseline assessment, the investigators will collect fasting blood samples to assess biomarkers related to gut, immune, and vascular health. Serum will also be used in mechanistic experiments where the investigators will treat endothelial cells in culture with serum from participants pre/post intervention and examine differences in gene and protein expression, as well as nitric oxide production. Next, vascular assessments (i.e., flow mediated dilation [FMD], pulse wave analysis [PWA], pulse wave velocity [PWV]) will be completed. This will conclude data collection and participants will be randomized to receive 6 weeks of supplemental inulin (a soluble fiber) or a placebo (maltodextrin). At 2-, 4-, and 6-weeks of the intervention, the same samples and measurements will be collected at in-lab visits. Stool samples will be collected at baseline and 6 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bryant Keirns, PhD; Phone Number: 765-285-8356; Email: bryant.keirns@bsu.edu

Study Locations

• United States
  • Indiana
    • Muncie, Indiana, United States, 47306
      • Recruiting
      • Health Professions Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 18-55 years old.
• BMI is 18.5-24.9 kg/m2 or >30kg/m2 (part 1). BMI > 30 kg/m2 (part 2)
• Not pregnant or expecting to become pregnant (females only).
• Not postmenopausal (females only).
• Have 0-1 risk factors based on blood pressure, blood sugar, triglycerides, and HDL-cholesterol ("good cholesterol").
• Have not been diagnosed with an advanced cardiometabolic condition (e.g., cardiovascular disease, type 2 diabetes).
• Have not been diagnosed with a chronic inflammatory or gastrointestinal condition (e.g., rheumatoid arthritis, inflammatory bowel disease).
• Do not regularly take anti-inflammatory drugs (more than 2x week) or are able to temporarily suspend use of anti-inflammatory drugs three days prior to the study visit.
• Have not taken antibiotics or probiotics in the last month.
• Do not use lipid-lowering drugs (e.g., statins), glucose-lowering drugs (e.g., metformin), or anti-hypertensive drugs.
• Do not use weight-loss drugs (e.g., Ozempic, Wegovy).
• Have not had any surgery that alters the stomach/gastrointestinal tract (e.g., gastric sleeve, gastric bypass).
• Do not use tobacco products or any illicit drugs.
• Do not have a pacemaker.
• Do not have dietary restrictions prohibiting consumption of the provided meal (e.g., vegan/vegetarian diets, gluten-free diet, relevant food allergies).
• Able to stay in the supine position in the dark for at least 10 minutes (related to vascular measurements)

Exclusion Criteria:

• Not 18-55 years old.
• BMI is not 18.5-24.9 kg/m2 or >30kg/m2 (part 1). BMI is not > 30 kg/m2 (part 2)
• Pregnant or expecting to become pregnant (females only).
• Postmenopausal (females only).
• Do not have 0-1 risk factors based on blood pressure, blood sugar, triglycerides, and HDL-cholesterol ("good cholesterol").
• Have been diagnosed with an advanced cardiometabolic condition (e.g., cardiovascular disease, type 2 diabetes).
• Have been diagnosed with a chronic inflammatory or gastrointestinal condition (e.g., rheumatoid arthritis, inflammatory bowel disease).
• Regularly take anti-inflammatory drugs (more than 2x week) or are unable to temporarily suspend use of anti-inflammatory drugs three days prior to the study visit.
• Have taken antibiotics or probiotics in the last month.
• Use lipid-lowering drugs (e.g., statins), glucose-lowering drugs (e.g., metformin), or anti-hypertensive drugs.
• Use weight-loss drugs (e.g., Ozempic, Wegovy).
• Have had any surgery that alters the stomach/gastrointestinal tract (e.g., gastric sleeve, gastric bypass).
• Use tobacco products or any illicit drugs.
• Have a pacemaker.
• Have dietary restrictions prohibiting consumption of the provided meal (e.g., vegan/vegetarian diets, gluten-free diet, relevant food allergies).
• Not able to stay in the supine position in the dark for at least 10 minutes (related to vascular measurements)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metabolically Healthy Obesity Group; Individuals with a body mass index greater than 30 kg/m2 and 0-1 of the following risk factors: blood pressure >130/85 mmHg, triglycerides > 150 mg/dL, glucose > 100 mg/dL, and HDL-C < 50 (females) or < 40 (males).	Dietary supplement: Inulin Supplementation; Half of participants in part 2 will recieve supplemental inulin or placebo (maltodextrin).; Dietary supplement: Maltodextrin (Placebo); Half of participants in part 2 will recieve supplemental inulin or placebo (maltodextrin).; Other: High-fat meal; All participants in part 1 (both metabolically healthy normal weight and metabolically healthy obesity) will consume a high-fat meal designed to invoke changes in gut, immune, and vascular parameters.
Active Comparator: Metabolically Healthy Normal Weight Group; Individuals with a body mass index between 18.5-24.9 kg/m2 and 0-1 of the following risk factors: blood pressure >130/85 mmHg, triglycerides > 150 mg/dL, glucose > 100 mg/dL, and HDL-C < 50 (females) or < 40 (males).	Other: High-fat meal; All participants in part 1 (both metabolically healthy normal weight and metabolically healthy obesity) will consume a high-fat meal designed to invoke changes in gut, immune, and vascular parameters.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum lipopolysaccharide binding protein	Part 1: The investigators will measure lipopolysaccharide binding protein at baseline and , 1-, 2-, 3-, 4-, 5-, and 6-hours after the meal. Part 2: The investigators will measure lipopolysaccharide binding protein at baseline and 2-, 4-, and 6-weeks post intervention.	Through study completion, up to 2 years
Serum interleukin-6	Part 1: The investigators will measure interleukin-6 at baseline and , 1-, 2-, 3-, 4-, 5-, and 6-hours after the meal. Part 2: The investigators will measure interleukin-6 at baseline and 2-, 4-, and 6-weeks post intervention.	Through study completion, up to 2 years.
Flow-mediated dilation	Part 1: The investigators will measure flow-mediated dilation at baseline and 2-, 4-, 6-hours after the meal. Part 2: The investigators will measure flow-mediated dilation at baseline and 2-, 4-, and 6-weeks post intervention.	Through study completion, up to 2 years
Serum C reactive protein	Part 2: The investigators will measure C reactive protein at baseline and 2-, 4-, and 6-weeks post intervention.	Through study completion, up to 2 years
Serum lipopolysaccharide	Part 1: The investigators will measure lipopolysaccharide at baseline and , 1-, 2-, 3-, 4-, 5-, and 6-hours after the meal. Part 2: The investigators will measure lipopolysaccharide at baseline and 2-, 4-, and 6-weeks post intervention.	Through study completion, up to 2 years
Serum TNF-alpha	The investigators will measure serum TNF-alpha at baseline and , 1-, 2-, 3-, 4-, 5-, and 6-hours after the meal. Part 2: The investigators will measure TNF-alpha at baseline and 2-, 4-, and 6-weeks post intervention.	Through study completion, up to 2 years
Serum zonulin	Part 2: The investigators will measure serum zonulin at baseline and 2-, 4-, and 6-weeks post intervention.	Through study completion, up to 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Augmentation Index	Part 1: The investigators will measure augmentation index at baseline and 2-, 4-, 6-hours after the meal. Part 2: The investigators will measure augmentation index at baseline and 2-, 4-, and 6-weeks post intervention.	Through study completion, up to 2 years
Pulse-wave velocity	Part 1: The investigators will measure pulse-wave velocity at baseline and 2-, 4-, 6-hours after the meal. Part 2: The investigators will measure pulse wave velocity at baseline and 2-, 4-, and 6-weeks post intervention.	Through study completion, up to 2 years
Serum soluble CD14	Part 1: The investigators will measure serum soluble CD14 at baseline and , 1-, 2-, 3-, 4-, 5-, and 6-hours after the meal. Part 2: The investigators will measure serum soluble sCD14 at baseline and 2-, 4-, and 6-weeks post intervention.	Through study completion, up to 2 years
Serum IL-1 beta	Part 1: The investigators will measure serum IL-1 beta at baseline and , 1-, 2-, 3-, 4-, 5-, and 6-hours after the meal. Part 2: The investigators will measure serum IL-1beta at baseline and 2-, 4-, and 6-weeks post intervention.	Through study completion, up to 2 years
Serum soluble VCAM-1	Part 1: The investigators will measure serum soluble VCAM-1 at baseline and , 1-, 2-, 3-, 4-, 5-, and 6-hours after the meal.	Through study completion, up to 2 years
Peripheral blood mononuclear cell transcriptome	Part 1: The investigators will measure interleukin-6 at baseline and 3-hours after the meal.	Through study completion, up to 2 years
Serum treated HAEC transcriptome	Part 1: The investigators will measure the HAEC transcriptome after treatment with baseline and 2-, 4-, 6-hour post-meal serum. Part 2: The investigators will measure the HAEC transcriptome after treatment with serum from baseline and 2-, 4-, and 6-weeks post intervention.	Through study completion, up to 2 years
Serum treated HAEC eNOS and NFkB protein expression	Part 1: The investigators will measure HAEC eNOS and NFkB protein expression after treatment with baseline and 2-, 4-, 6-hour post-meal serum. Part 2: The investigators will measure HAEC eNOS and NFkB protein expression after treatment with serum from baseline and 2-, 4-, and 6-weeks post intervention.	Through study completion, up to 2 years
Microbiome composition (shotgun sequencing)	Part 1: The investigators will determine microbiome composition once within one week of participants completing the meal trial. Part 2: The investigators will measure microbiome composition at baseline and 6-weeks post intervention.	Through study completion, up to 2 years
Serum treated HAEC nitric oxide production	Part 1: The investigators will measure the HAEC nitric oxide production after treatment with baseline and 2-, 4-, 6-hour post-meal serum. Part 2: The investigators will measure HAEC nitric oxide production after treatment with serum from baseline and 2-, 4-, and 6-weeks post intervention.	Through study completion, up to two years.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body fat percent	Part 1: The investigators will measure body fat percent using Dual-Energy X-ray Absorptiometry. Part 2: The investigators will measure body fat percent using Dual-Energy X-ray Absorptiometry at baseline and 6-weeks post intervention.	Through study completion, up to 2 years.

Collaborators and Investigators

• Sponsor: Ball State University
• Investigators: Principal Investigator: Bryant Keirns, PhD, Ball State University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: April 16, 2026
• First Submitted That Met QC Criteria: April 23, 2026
• First Posted (Actual): April 30, 2026

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: obesity; vascular function; Intestinal permeability; Gut-vascular axis
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity, Metabolically Benign; Obesity; maltodextrin
• Other Study ID Numbers: IRB-FY2026-239

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: ClinicalTrials.gov NCBI BioProject NCBI Reference Sequence Open Science Framework (general) Sequence Read Archive (SRA)
• IPD Sharing Time Frame: 12/31/2027

Drug and device information, study documents

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