Fecal microbiota transplantation for the improvement of metabolism in obesity: The FMT-TRIM double-blind placebo-controlled pilot trial
Fecal microbiota transplantation for the improvement of metabolism in obesity: The FMT-TRIM double-blind placebo-controlled pilot trial
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DOI：
10.1371/journal.pmed.1003051
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发表时间：
2020-03-01
期刊：
影响因子：
15.8
通讯作者：
Hohmann, Elizabeth L.
中科院分区：
文献类型：
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作者：
Yu, Elaine W.;Gao, Liu;Hohmann, Elizabeth L.
背景调节肠道微生物群是否能影响全身代谢引起了人们的强烈兴趣。我们调查了每周口服粪便微生物群移植（FMT）胶囊从健康瘦供体和他们的能力，改变肠道微生物群和改善肥胖患者的代谢结果的安全性。方法和findingsFMT-TRIM是一个为期12周的双盲随机安慰剂对照试验口服FMT胶囊在一个单一的美国学术医疗中心进行。在2016年8月至2018年4月期间，我们将24名肥胖和轻度-中度胰岛素抵抗（胰岛素抵抗[HOMA-IR]的稳态模型评估在2.0至8.0之间）的成年人随机分配至每周健康瘦供体FMT与安慰剂胶囊，持续6周。通过意向治疗评估的主要结局是通过高胰岛素正葡萄糖钳夹测量的0 - 6周胰岛素敏感性的变化。在第0、6和12周评价其他代谢参数，包括HbA 1c、体重、通过双能X线吸收测定法测定的身体组成和通过间接热量测定法测定的静息能量消耗。连续收集粪便样品并通过16 S V4 rRNA测序进行评价。我们的研究人群中71%为女性，FMT组和安慰剂组的平均基线BMI分别为38.8 +/- 6.7 kg/m2和41.3 +/- 5.1 kg/m2。与安慰剂组相比，FMT组的胰岛素敏感性无统计学显著改善（FMT组+5% 12% vs安慰剂组-3% +/- 32%，平均差异9%，95% CI -5%至28%，p = 0.16）。对于大多数其他次要代谢结局，包括HOMA-IR，两组之间没有统计学显著差异（平均差异0.2，95% CI -0.9至0.9，p = 0.96）和身体组成（瘦体重平均差异-0.1 kg，95% CI -1.9至1.6 kg，p = 0.87;脂肪量平均差异1.2 kg，95% CI -0.6至3.0 kg，p = 0.18）。我们观察到FMT接受者中供体细菌群的可变植入，这在整个12周的研究中持续存在。不良事件（AE）无显著差异（10 vs 5，p = 0.09），无FMT相关严重AE。这个试点研究的局限性是小样本量，包括参与者相对温和的胰岛素抵抗，缺乏并发的饮食intervention.ConclusionsWeekly管理FMT胶囊在成人肥胖的结果在肠道菌群植入在大多数收件人至少12周。尽管植入，我们在研究期间没有观察到临床显著的代谢效应。
BackgroundThere is intense interest about whether modulating gut microbiota can impact systemic metabolism. We investigated the safety of weekly oral fecal microbiota transplantation (FMT) capsules from healthy lean donors and their ability to alter gut microbiota and improve metabolic outcomes in patients with obesity.Methods and findingsFMT-TRIM was a 12-week double-blind randomized placebo-controlled pilot trial of oral FMT capsules performed at a single US academic medical center. Between August 2016 and April 2018, we randomized 24 adults with obesity and mild-moderate insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] between 2.0 and 8.0) to weekly healthy lean donor FMT versus placebo capsules for 6 weeks. The primary outcome, assessed by intention to treat, was change in insulin sensitivity between 0 and 6 weeks as measured by hyperinsulinemic euglycemic clamps. Additional metabolic parameters were evaluated at 0, 6, and 12 weeks, including HbA1c, body weight, body composition by dual energy X-ray absorptiometry, and resting energy expenditure by indirect calorimetry. Fecal samples were serially collected and evaluated via 16S V4 rRNA sequencing. Our study population was 71% female, with an average baseline BMI of 38.8 +/- 6.7 kg/m(2) and 41.3 +/- 5.1 kg/m(2) in the FMT and placebo groups, respectively. There were no statistically significant improvements in insulin sensitivity in the FMT group compared to the placebo group (+5% 12% in FMT group versus -3% +/- 32% in placebo group, mean difference 9%, 95% CI -5% to 28%, p = 0.16). There were no statistically significant differences between groups for most of the other secondary metabolic outcomes, including HOMA-IR (mean difference 0.2, 95% CI -0.9 to 0.9, p = 0.96) and body composition (lean mass mean difference -0.1 kg, 95% CI -1.9 to 1.6 kg, p = 0.87; fat mass mean difference 1.2 kg, 95% CI -0.6 to 3.0 kg, p = 0.18), over the 12-week study. We observed variable engraftment of donor bacterial groups among FMT recipients, which persisted throughout the 12-week study. There were no significant differences in adverse events (AEs) (10 versus 5, p = 0.09), and no serious AEs related to FMT. Limitations of this pilot study are the small sample size, inclusion of participants with relatively mild insulin resistance, and lack of concurrent dietary intervention.ConclusionsWeekly administration of FMT capsules in adults with obesity results in gut microbiota engraftment in most recipients for at least 12 weeks. Despite engraftment, we did not observe clinically significant metabolic effects during the study.