Liggins Institute, University of Auckland, Auckland, New Zealand.
A Better Start - National Science Challenge, University of Auckland, Auckland, New Zealand.
BMJ Open. 2019 Apr 20;9(4):e026174. doi: 10.1136/bmjopen-2018-026174.
Animal studies showed that germ-free mice inoculated with normal mouse gut bacteria developed obesity, insulin resistance and higher triglyceride levels, despite similar food intake. In humans, an association has been found between obesity and gut microbiome dysbiosis. However, gut microbiome transfer has not been evaluated for the treatment of human obesity. We will examine the effectiveness of gut microbiome transfer using encapsulated material for the treatment of obesity in adolescents.
A two-arm, double-blind, placebo-controlled, randomised clinical trial of a single course of gut microbiome transfer will be conducted in 80 obese [body mass index (BMI) ≥30 kg/m] adolescents (males and females, aged 14-18 years) in Auckland, New Zealand. Healthy lean donors (males and females, aged 18-28 years) will provide fresh stool samples from which bacteria will be isolated and double encapsulated. Participants (recipients) will be randomised at 1:1 to control (placebo) or treatment (gut microbiome transfer), stratified by sex. Recipients will receive 28 capsules over two consecutive mornings (~14 mL of frozen microbial suspension or saline). Clinical assessments will be performed at baseline, 6, 12 and 26 weeks, and will include: anthropometry, blood pressure, fasting metabolic markers, dietary intake, physical activity levels and health-related quality of life. Insulin sensitivity (Matsuda index), gut microbiota population structure characterised by 16S rRNA amplicon sequencing and body composition (using dual-energy X-ray absorptiometry) will be assessed at baseline, 6, 12 and 26 weeks. 24-hour ambulatory blood pressure monitoring will be performed at baseline and at 6 weeks. The primary outcome is BMI SD scores (SDS) at 6 weeks, with BMI SDS at 12 and 26 weeks as secondary outcomes. Other secondary outcomes include insulin sensitivity, adiposity (total body fat percentage) and gut microbial composition at 6, 12 and 26 weeks. Statistical analysis will be performed on the principle of intention to treat.
Ethics approval was provided by the Northern A Health and Disability Ethics Committee (Ministry of Health, New Zealand; 16/NTA/172). The trial results will be published in peer-reviewed journals and presented at international conferences.
ACTRN12615001351505; Pre-results.
动物研究表明，即使摄入的食物相同，无菌小鼠接种正常的小鼠肠道细菌后会发展为肥胖、胰岛素抵抗和更高的甘油三酯水平。在人类中，肥胖与肠道微生物组失调之间存在关联。然而，尚未评估肠道微生物组转移用于治疗人类肥胖。我们将使用封装材料评估肠道微生物组转移治疗青少年肥胖的效果。
这是一项在新西兰奥克兰进行的、针对 80 名肥胖青少年（男性和女性，年龄 14-18 岁，BMI≥30kg/m²）的、为期 6 周的、双盲、安慰剂对照、随机临床试验。健康的瘦供体（男性和女性，年龄 18-28 岁）将提供新鲜粪便样本，从中分离并双重封装细菌。参与者（受赠者）将按照 1:1 的比例随机分为对照组（安慰剂）或治疗组（肠道微生物组转移），按性别分层。受赠者将在连续两天的早上（约 14ml 冷冻微生物混悬液或生理盐水）各接受 28 粒胶囊。临床评估将在基线、6、12 和 26 周进行，包括：人体测量、血压、空腹代谢标志物、饮食摄入、身体活动水平和健康相关生活质量。胰岛素敏感性（Matsuda 指数）、16S rRNA 扩增子测序评估的肠道微生物种群结构和身体成分（使用双能 X 射线吸收法）将在基线、6、12 和 26 周进行评估。基线和 6 周时进行 24 小时动态血压监测。主要结局是 6 周时的 BMI SDS，次要结局包括 12 周和 26 周时的 BMI SDS、胰岛素敏感性、肥胖（体脂百分比）和肠道微生物组成。将按照意向治疗原则进行统计分析。
该试验已获得北岛健康和残疾伦理委员会（新西兰卫生部；16/NTA/172）的批准。试验结果将发表在同行评议的期刊上，并在国际会议上发表。
ACTRN12615001351505；预结果。
