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

Launched by UNIVERSITY HOSPITAL, GENTOFTE, COPENHAGEN · Jan 15, 2025

Keywords

ClinConnect Summary

This study, called GUTBBB, is an observational project in Denmark that wants to understand how obesity might affect the barriers that protect the gut and the brain, and how this relates to inflammation and brain health. It will compare 25 adults with obesity (BMI over 35) to 25 lean adults (BMI 20–25), all aged 40–70 and matched by age and gender. The researchers will look at how changes in these barriers relate to inflammation and markers of nerve health, to see if obesity could influence brain-related risk factors.

Participants will go through three study days plus a screening visit. At screening, doctors check health, weight, body fat, and do blood tests. Visit 1 includes providing a stool sample, drinking a solution to test gut permeability, urine collection, and cognitive and mood tests. Visit 2 uses an MRI with a contrast dye to assess the blood-brain barrier. A range of blood tests will measure gut- and brain-related markers, inflammation, and metabolism to explore how these measures are connected. Eligibility includes adults 40–70 without diabetes or inflammatory gut diseases, not pregnant, not using certain medications, and not able to have MRI scans; smokers are not eligible. The study is led by University Hospital Gentofte and the University of Copenhagen, with recruitment by invitation, and is expected to complete around May 2026.

Gender

ALL

Eligibility criteria

• • 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