Understanding How Gut and Brain Barriers Are Linked to Inflammation in Obesity (GUTBBB)

Exploring the Interplay Between Gut Barrier and Blood-Brain Barrier Integrity, Systemic Inflammation, and Cognitive Function in Obesity

The goal of this observational study is to understand how obesity affects the function of the gut and blood-brain barriers in adults. These barriers protect the body and brain from harmful substances, and changes in their function may lead to inflammation and increased risk of chronic diseases. The study will include 25 participants with obesity (BMI over 35) and 25 healthy participants (BMI 20-25) matched by age and gender.

The main questions it aims to answer are:

• How does obesity affect the blood-brain barrier and its connection to cognitive and psychopathological status?
• Does increased gut permeability lead to higher inflammation levels?
• Does obesity increase the permeability of the gut barrier?

Researchers will compare results from participants with obesity to healthy participants to determine how obesity impacts barrier function, inflammation, and overall health.

Participants will:

Attend three visits over several days, including:

• Screening visit: A health examination with weight, height, blood pressure, blood tests, and a scan to assess body fat distribution.
• Visit 1: Provide a stool sample, drink a sugar solution to assess gut permeability, collect urine samples, and take cognitive as well as psychopathological tests.
• Visit 2: Undergo an MRI scan to assess the blood-brain barrier and its function.

The study aims to identify how obesity-related changes in these barriers contribute to health risks.

Study Overview

• Status: Completed
• Conditions: Neurodegenerative Disease; Obesity (Disorder); Blood Brain Barrier; Intestinal Barrier Dysfunction; Systemic Inflammation Markers

Detailed Description

The study is a cross-sectional study including individuals with obesity and lean healthy controls. It is planned to recruit 25 individuals with a BMI above 35 kg/m2 and 25 lean healthy gender- and age-matched individuals with a BMI between 20-25 kg/m2. Given the extensive nature of these examinations, which include the lactulose/sucralose-mannitol test, DCE-MRI, metabolic and cognitive assessments, they will be conducted on three separate study days, in random order, and with fixed time intervals between each study day. The study employs a comprehensive approach to assess gut barrier integrity using the lactulose/sucralose-mannitol test to evaluate barrier permeability and absorptive surface area, complemented by measuring biomarkers related to gut integrity and microbial-immune interaction. Additionally, the study analyses circulating proinflammatory biomarkers and microbial genetic material to understand systemic inflammation and bacterial translocation in obesity. The integrity of the BBB is examined using DCE-MRI to detect alterations in obesity and investigate correlation between BBB permeability and obesity-related neurological conditions. Cognitive functions are assessed through tests that evaluate domains like processing speed and memory and psychopathological tests will evaluate depressive and anxiety symptoms. These tests explore the potential impact of obesity on the central nervous system. Metabolic and physiological measurements, including glucose levels, haemoglobin A1c, and body composition, provide insights into the metabolic effects of obesity and its broader physiological implications.

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• Denmark
  • Hellerup, Denmark, 2900
    • Herlev Gentofte Hospital

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Older individuals with and without obesity

Description

Inclusion criteria for individuals living with obesity

• BMI > 35 kg/m2, bioimpedance-assessed body fat > 30% (men) or > 40% (women), and hip/waist-ratio > 0.85
• Age ≥40 and ≦70 years
• Sterilised or postmenopausal women (> 12 months amenorrhoea or females ≥ 60 years of age) or women who are sexually abstinent during the entire study period or are practicing non-hormonal contraception (no contraceptive pill, no hormonal intrauterine device) during the entire study period
• Able to understand written participant information and give signed informed consent.

Inclusion criteria for lean healthy controls

• BMI 20-25 kg/m2, bioimpedance-assessed body fat < 30% (men) or < 40% (women), and hip/waist-ratio < 0.85
• Age ≥40 and ≦70 years
• Sterilised or postmenopausal women (> 12 months amenorrhoea or females ≥ 60 years of age) or women who are sexually abstinent during the entire study period or are practicing non-hormonal contraception (no contraceptive pill, no hormonal intrauterine device) during the entire study period

Exclusion Criteria:

• Diagnosis of diabetes mellitus type 1 or type 2.
• Inflammatory gastrointestinal conditions such as Crohn's disease, ulcerative colitis, clinically significant food allergies, candidiasis, etc.
• Previous bariatric surgery, or surgeries involving the removal of intestinal tissue
• The use of weight loss-inducing medication such as GLP-1 receptor agonists, bupropion/naltrexone, and orlistat within 90 days prior to screening
• Planned elective surgery during the study period with the exception of dermatosurgical, ENT (ear, nose, throat) or dental procedures not requiring general anaesthesia and/or perioperative antibiotic treatment
• Chronic systemic inflammatory diseases (e.g. rheumatoid arthritis) and other conditions significantly affecting inflammation status or immunoregulation (severe allergies, status post transplantation etc.)
• History of sleep disorders
• Chronic infectious diseases such as hepatitis, HIV etc.
• Use of proton pump inhibitors, metformin, anti-biotic, lipid-lowering statins, laxatives, antihistamines, paracetamol, aspirin, statins, tricyclic antidepressants, selective serotonin reuptake inhibitor antidepressants and any other medications correlated to changes in faecal microbiome diversity for the period of the study and within 20 days prior to screening
• Active use of nicotine products, including but not limited to cigarettes, vapes, or any other form of nicotine consumption.
• Abuse of alcohol and/or drugs, or any other co-existing conditions that will make the individual unsuitable to participate in the study, as deemed by the investigators
• Pregnancy or desire to become pregnant during the study period
• Breastfeeding
• Any concomitant disease or treatment that, at the discretion of the investigators, might jeopardise the participant's safety during the study
• Mental incapacity or language barriers that preclude adequate understanding or cooperation, or unwillingness to comply with study requirements
• Body weight above the MRI scanner's maximum capacity of 140 kg or claustrophobia at a level, which makes MRI scans impossible
• Severe kidney disease with increased serum creatinine and low estimated glomerular filtration rate (GFR) (<60ml/min/1.73m2)
• Magnetic foreign objects in the body (e.g. pacemaker, metal implants from operation, etc.)
• Adherence to a restrictive diet (e.g. ketogenic diet, vegan diet, raw diet, low FODMAP diet, and paleo diet) which is significantly correlated to changes in faecal microbiome diversity 7.2.3. Criteria for discontinuation in the study
• Withdrawal of informed consent
• Pregnancy
• Any safety consideration as assessed by the investigators
• Any exclusion criterion developing or being diagnosed during the course of the study
• Non-compliance with the study protocol as deemed by the investigators

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Individuals living with obesity; BMI > 35 kg/m2, bioimpedance-assessed body fat > 30% (men) or > 40% (women), and hip/waist-ratio > 0.85
Individuals with lean bodies; BMI 20-25 kg/m2, bioimpedance-assessed body fat < 30% (men) or < 40% (women), and hip/waist-ratio < 0.85

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BBB permeability	Differences in BBB permeability using Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) between individuals with and without obesity	25 minutes post contrast administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between BBB permeability and gut barrier permeability	Ki values from DCE-MRI and Lactulose/Mannitol ratio from Lactulose/Sucralose-Mannitol test.	25 minutes post contrast administration and 0-5h Lactulose/Mannitol ratio
Correlation between BBB permeability and gut barrier permeability	Ki values from DCE-MRI and Lactulose/Mannitol ratio from Lactulose/Sucralose-Mannitol test.	25 minutes post contrast administration and 5-24h Lactulose/Mannitol ratio
Correlation between BBB permeability and gut barrier permeability	Ki values from DCE-MRI and quantities of plasma Zonulin	25 minutes post contrast administration and baseline (fasting) Zonulin
Correlation between BBB permeability and gut barrier permeability	Ki values from DCE-MRI and quantities of plasma Citrulline	25 minutes post contrast administration and baseline (fasting) Citrulline
Correlation between BBB permeability and gut barrier permeability	Ki values from DCE-MRI and quantities of plasma Regenerating islet-derived protein 3-alpha	25 minutes post contrast administration and baseline (fasting) Regenerating islet-derived protein 3-alpha
Correlation between BBB permeability and gut barrier permeability	Ki values from DCE-MRI and quantities of plasma Lipopolysaccharide binding protein	25 minutes post contrast administration and baseline (fasting) LBP
Correlation between BBB permeability and gut barrier permeability	Ki values from DCE-MRI and quantities of plasma soluble cluster of differentiation 14	25 minutes post contrast administration and baseline (fasting) sCD14
Correlation between BBB permeability and gut barrier permeability	Ki values from DCE-MRI and full blood bacterial DNA	25 minutes post contrast administration and postprandial AUC of full blood bacterial DNA
Correlation between BBB permeability and markers of neuronal damage	Ki values from DCE-MRI and quantities of plasma Amyloid beta	25 minutes post contrast administration and baseline (fasting) Amyloid beta
Correlation between BBB permeability and markers of neuronal damage	Ki values from DCE-MRI and quantities of plasma P-Tau	25 minutes post contrast administration and baseline (fasting) P-Tau
Correlation between BBB permeability and markers of neuronal damage	Ki values from DCE-MRI and quantities of plasma NfL	25 minutes post contrast administration and baseline (fasting) NfL
Correlation between BBB permeability and markers of neuronal damage	Ki values from DCE-MRI and quantities of plasma GFAP	25 minutes post contrast administration and baseline (fasting) GFAP
Correlation between BBB permeability and markers of neuronal damage	Ki values from DCE-MRI and quantities of plasma Alfa-Synuclein	25 minutes post contrast administration and baseline (fasting) Alfa-Synuclein
Correlation between BBB permeability and systemic inflammation	Ki values from DCE-MRI and quantities of plasma High sensitivity CRP	25 minutes post contrast administration and baseline (fasting) HS CRP
Correlation between BBB permeability and systemic inflammation	Ki values from DCE-MRI and quantities of plasma TNF alfa	25 minutes post contrast administration and baseline (fasting) TNF alfa
Correlation between BBB permeability and systemic inflammation	Ki values from DCE-MRI and quantities of plasma IL 1 beta	25 minutes post contrast administration and baseline (fasting) IL 1 beta
Correlation between BBB permeability and metabolic markers	Ki values from DCE-MRI and Body mass index	25 minutes post contrast administration and body mass index
Correlation between BBB permeability and metabolic markers	Ki values from DCE-MRI and bioimpedance-assessed body fat	25 minutes post contrast administration and bioimpedance-assessed body fat
Correlation between BBB permeability and metabolic markers	Ki values from DCE-MRI and plasma Glucose	25 minutes post contrast administration and baseline (fasting) Glucose
Correlation between BBB permeability and metabolic markers	Ki values from DCE-MRI and plasma HbA1c	25 minutes post contrast administration and baseline (fasting) HbA1c
Correlation between BBB permeability and metabolic markers	Ki values from DCE-MRI and plasma Insulin	25 minutes post contrast administration and baseline (fasting) Insulin
Correlation between BBB permeability and metabolic markers	Ki values from DCE-MRI and plasma HDL cholesterol	25 minutes post contrast administration and baseline (fasting) HDL cholesterol
Correlation between BBB permeability and metabolic markers	Ki values from DCE-MRI and plasma Triglycerides	25 minutes post contrast administration and baseline (fasting) Triglycerides
Correlation between BBB permeability and metabolic markers	Ki values from DCE-MRI and plasma LDL cholesterol	25 minutes post contrast administration and baseline (fasting) LDL cholesterol
Correlation between BBB permeability and metabolic markers	Ki values from DCE-MRI and plasma VLDL cholesterol	25 minutes post contrast administration and baseline (fasting) VLDL cholesterol
Correlation between BBB permeability and metabolic markers	Ki values from DCE-MRI and plasma ALT	25 minutes post contrast administration and baseline (fasting) ALT

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Collaborators: University of Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2025
• Primary Completion (Actual): February 17, 2026
• Study Completion (Actual): February 17, 2026

Study Registration Dates

• First Submitted: January 9, 2025
• First Submitted That Met QC Criteria: January 15, 2025
• First Posted (Actual): January 22, 2025

Study Record Updates

• Last Update Posted (Actual): February 18, 2026
• Last Update Submitted That Met QC Criteria: February 16, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: microbiome; systemic inflammation; bacterial translocation; intestinal barrier function; blood brain barrier function
• Additional Relevant MeSH Terms: Nervous System Diseases; Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Neurodegenerative Diseases
• Other Study ID Numbers: GUTBBB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No