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

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.

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