Gut Organoid and Microbiome Interactions in Hypertension

Gut Inflammation and Gut-Gut Microbiome Interactions in the Pathogenesis of Hypertension

The study compared basic properties of gut epithelia of hypertensive and normotensive reference subjects. The study determined if there are fundamental differences in the gut epithelium in hypertension compared to normotension. Specifically, this study examined gene expression profiles of gut organoids derived from biopsy samples of hypertensive and normotensive individuals undergoing clinically indicated colonoscopy.

Study Overview

• Status: Completed
• Conditions: Hypertension; Gut Inflammation
• Intervention / Treatment: Other: Gene Expression

Detailed Description

This investigated whether there is a difference in gut epithelia between individuals with and without high blood pressure by comparing colonic biopsy samples from. The study was conducted among adults undergoing routine elective colonoscopy at the University of Florida. Participants were classified into high blood pressure (HBP) and normotensive (REF) groups based on blood pressure criteria defined by the 2017 ACC/AHA guidelines.

The study had two primary aims. Aim 1 was to evaluate whether gene expression patterns in the gut epithelium differ between hypertensive and normotensive individuals using RNA sequencing. Aim 2 was to assess whether gut organoids-three-dimensional epithelial cultures derived from colonic biopsies-exhibit different growth rates and proportions, using immunohistochemistry and fluorescence-activated cell sorting (FACS).

Biopsy specimens were collected during clinically indicated colonoscopies. Tissue samples were processed immediately after collection: one portion was snap-frozen for RNA isolation and sequencing; the other was used to establish gut organoid cultures. Data were coded and stored in a secure, encrypted database with all identifiers removed to protect confidentiality, in compliance with HIPAA regulations.

Although the study protocol initially planned to recruit 60 participants, a total of 35 subjects were successfully enrolled-16 with high blood pressure (HBP) and 19 normotensive (REF) participants. All provided adequate biopsy material for gene expression analysis.

• Study Type: Observational
• Enrollment (Actual): 35

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Hypertensive and normotensive patients who routinely undergo scheduled elective colonoscopy (for different, not selected reasons)

Description

Inclusion Criteria:

• Inclusion/exclusion criteria for hypertension participants
• Ages: 18-80 years old with a weight greater than or equal to 110 lbs
• Diagnosis of hypertension or without hypertension for the reference cohort. 2017 ACC/AHA (American College of Cardiology/American Heart Association) definition for hypertension (systolic blood pressure ≥130 mmHg and/or diastolic BP ≥80 mmHg) will be used.
• Scheduled elective colonoscopy

Exclusion Criteria:

• Hypertensive or reference individuals with history of autoimmune disease or other chronic inflammatory conditions.
• Pregnant or have been pregnant in the last six months.
• Antibiotic treatment within two months of study enrollment
• Currently taking a medication (e.g. antibiotic, anti-inflammatory agents, glucocorticoids, other immune modulating medications, antacids or proton pump inhibitor drugs like Prilosec) known to modify gut microbiota.
• Unwilling to discontinue using probiotics for at least two weeks before scheduled biopsy.
• History of intestinal surgery, inflammatory bowel disease, celiac disease, lactose intolerance, chronic pancreatitis or other malabsorption disorder.
• History of blood transfusion within 4 weeks.
• Subjects who, in the opinion of the investigator, will be uncooperative or unable to comply with study procedures

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients undergoing routine colonoscopy; Participants were adults undergoing routine screening colonoscopy who met study eligibility criteria and provided written informed consent. Based on their blood pressure status, participants were categorized into two groups: individuals without hypertension (normotensive group) and individuals with high blood pressure (hypertensive group), defined according to the 2017 ACC/AHA guidelines

Other: Gene Expression; Gene expression analysis of biopsy specimens obtained during routine colonoscopy examination

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differential Gene Expression in Gut Epithelium	Number of differentially expressed genes identified through RNA sequencing of colonic epithelial tissue obtained during colonoscopy. Expression profiles were compared between individuals with High Blood pressure (HBP) (hypertensive group) and normotensive reference (REF) participants. Genes were considered differentially expressed if they met criteria of false discovery rate (FDR)-adjusted p-value < 0.05 and absolute fold change ≥ 1.5.	At time of colonoscopy (single visit)
Growth Rates of Gut Organoids	To compare growth rates and proportions of gut organoids derived from High Blood pressure (HBP) vs. normotensive (REF) participants.	Within days to weeks post-biopsy (in vitro culture period)

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Carl Pepine, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2021
• Primary Completion (Actual): April 8, 2022
• Study Completion (Actual): April 21, 2024

Study Registration Dates

• First Submitted: July 28, 2020
• First Submitted That Met QC Criteria: August 3, 2020
• First Posted (Actual): August 4, 2020

Study Record Updates

• Last Update Posted (Estimated): September 29, 2025
• Last Update Submitted That Met QC Criteria: September 8, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension; Genetic Phenomena; Gene Expression
• Other Study ID Numbers: IRB201903360 -N; R01HL132448 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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