Gut Bugs Trial - Gut microbiome transfer for the treatment of adolescent obesity

INTERVENTION: We will recruit 8 donors (4 males and 4 females), as recipients will only receive gut microbiome from donors of the same sex. Donors will be selected based on a strict inclusion criteria. Each donor is expected to produce a wet stool sample weighing 100‐150 g. Stool samples will be collected and immediately processed for encapsulation. Capsules from each sample will be individually coded, so that each recipient will receive an equal number of capsules (n=7) from each of the 4 same sex donors. Immediately after donation, stools are placed in normal saline, blended, and sieved to remove particulate matter. Samples are then differentially centrifuged to isolate a bacterial pellet. The bacterial pellet is suspended in normal saline (containing 15% glycerol – a cryoprotectant) at 0.5 g wet weight/ml before being dispensed into size 0 DRcapsTM capsules (Capsugel Inc, Sydney, Australia). The size 0 capsules are closed and secondarily sealed in size 00 DRcapsTM capsules. These capsules mask taste, odour, and visual appearance, and are designed to remain intact during passage through the stomach, delivering their contents to the intestine. Capsules are stored frozen at ‐80°C. We will recruit 80 obese adolescents aged 14‐18 with BMI more or equal 30 kg/m2 randomised into two groups: control (placebo – saline) or treatment (gut microbiome transfer). Participants (recipients) will undergo bowel cleansing with Glycoprep‐C® the evening before treatment initiation. The next morning, at the clinical research unit, each recipient in the placebo group will receive saline capsules, while those in the treatment group will receive gut microbiome capsules. Each recipient will receive a total of 28 capsules administered over two consecutive mornings under direct supervision from research staff, specifically 16 capsules on the first morning and 12 capsules on the second morning. Recipients will be fasting overnight for at least 8 hours prior to taking each set of capsules at the clinical research unit. After treatment, all recipients will remain fasting for another 2 hours. Recipients will be advised not to change their diet and physical activity and behaviour during the trial. CONDITION: Obesity (BMI more or equal to 30 kg/m2) PRIMARY OUTCOME: BMI SDS at 6 weeks ; ; SECONDARY OUTCOME: blood pressure at 6, 12, and 26 weeks ; ; Clinic resting systolic and diastolic blood pressure will be measured at all assessments using the same oscillometric digital blood pressure monitor (ri‐champion® N; Riester, Jungingen, Germany) with an appropriately‐sized cuff on the extended non‐dominant arm. ; ; BMI SDS at 12, and 26 weeks ; changes in bowel movement at 6, 12, and 26 weeks ; ; Changes in bowel movement will be assessed via the bowel movements questionnaire. gut microbial composition at 6, 12, and 26 weeks ; ; Gut microbial composition will be evaluated via 16S rRNA amplicon sequencing. ; ; health‐related quality of life at 6, 12, and 26 weeks ; ; Health‐related quality of life will be assessed via questionnaires including EPOCH Measure of Adolescent Well‐Being and Pediatric Quality of Life Inventory (PedsQL). ; IBS symptoms at 6, 12, and 26 weeks ; ; IBS symptoms will be assessed via the Birmingham IBS symptom questionnaire. inflammatory markers at 6, 12, and 26 weeks ; ; Inflammatory markers will be assessed by measurement of uric acid and high‐sensitivity C‐reactive protein (hsCRP) using plasma assays. ; ; insulin sensitivity at 6, 12, and 26 weeks ; ; Insulin sensitivity will be assessed in all recipients using the Matsuda index from a 75‐g oral glucose tolerance test (OGTT). ; ; lipid profile at 6, 12, and 26 weeks ; ; Lipid profile will be assessed by measurement of total cholesterol, high‐density lipoprotein cholesterol [HDL‐C], low‐density lipoprotein cholesterol [LDL‐C], and triglycerides using plasma assays. ; ; liver function at 6, 12, and 26 weeks ; ; Liver function will be assessed by measurement of gamma‐glutamyl transferase (GGT), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate transaminase (AST) using plasma assays. ; ; total body fat percentage [from whole‐body dual‐energy x‐ray absorptiometry (DXA)] at 6, 12, and 26 weeks ; ; INCLUSION CRITERIA: Recipient subjects (40 males and 40 females): • Age 14‐18 years • Obese (BMI: greater or equal than 30 kg/m2) • Post‐pubertal (Tanner stage 5) Gut microbiome donors: • Age 18‐28 years • BMI greater than 18.5 kg/m2 and less than 30.0 kg/m2 • Total body fat percentage: less than or equal to 29% for females; less than or equal to 19% for males • Regular exercise (moderate to vigorous physical activity for at least 3.5 hours/week) • Regular Bowel Habit (at least 1 every 2 days) • Intake greater than or equal to 4 portions of fruit and/or vegetables per day