BACKGROUND & AIMS Studies in mice have shown that the intestinal microbiota can contribute to obesity via the anorexigenic gut hormone glucagon-like peptide 1 (GLP1) and bile acids, which affect lipid metabolism. We performed a randomized, placebo-controlled, pilot study of the effects of fecal microbiota transplantation (FMT) in obese, metabolically uncompromised patients. METHODS We performed a double-blind study of 22 obese patients (body mass index [BMI] ≥5 kg/m2) without a diagnosis of diabetes, nonalcoholic steatohepatitis, or metabolic syndrome. Participants were assigned randomly (1:1) to groups that received FMT by capsules (induction dose of 30 capsules at week 4 and maintenance dose of 12 capsules at week 8) or placebo capsules. FMT capsules were derived from a single lean donor (BMI, 17.5 kg/m2). Patients were followed up through week 26; the primary outcome was safety. Stool and serum samples were collected from patients at baseline and at weeks 1, 4, 6, 8, and 12 after administration of the first dose of FMT or placebo and analyzed by 16S RNA gene sequencing. Stool and serum samples were analyzed for metabolomics by liquid chromatography-mass spectrometry. Additional outcomes were the change in area under the curve for GLP1 at week 12. RESULTS We observed no significant differences in adverse events between patients who received FMT vs placebo. There was no increase in the area under the curve of GLP1 in either group. Patients who received FMT had sustained shifts in microbiomes associated with obesity toward those of the donor (P < .001). Patients who received FMT had a sustained decrease in stool levels of taurocholic acid (P < .05) compared with baseline; bile acid profiles began to resemble those of the donor more closely. We did not observe significant changes in mean BMI at week 12 in either group. CONCLUSIONS In a placebo-controlled pilot study, we found that FMT capsules (derived from a lean donor) were safe but did not reduce BMI in obese metabolically uncompromised patients. The FMT capsules were well tolerated and led to sustained changes in the intestinal microbiome and bile acid profiles that were similar to those of the lean donor. ClinicalTrials.gov number: NCT02741518.

中文翻译：

---

口服胶囊粪便微生物群移植对肥胖患者的影响。

背景和目的 小鼠研究表明，肠道微生物群可通过产生厌食性肠道激素胰高血糖素样肽 1 (GLP1) 和胆汁酸导致肥胖，后者会影响脂质代谢。我们对粪便微生物群移植 (FMT) 对肥胖、代谢未受损患者的影响进行了一项随机、安慰剂对照的初步研究。方法 我们对 22 名未诊断为糖尿病、非酒精性脂肪性肝炎或代谢综合征的肥胖患者（体重指数 [BMI] ≥ 5 kg/m2）进行了一项双盲研究。参与者被随机 (1:1) 分配到接受 FMT 胶囊（第 4 周诱导剂量 30 粒胶囊和第 8 周维持剂量 12 粒胶囊）或安慰剂胶囊的组。FMT 胶囊来自单个瘦肉供体（BMI，17.5 kg/m2）。患者随访至第 26 周；主要结果是安全性。在基线时以及在施用第一剂 FMT 或安慰剂后第 1、4、6、8 和 12 周收集患者的粪便和血清样本，并通过 16S RNA 基因测序进行分析。通过液相色谱-质谱法分析粪便和血清样品的代谢组学。其他结果是第 12 周 GLP1 曲线下面积的变化。 结果 我们观察到接受 FMT 与安慰剂的患者之间的不良事件没有显着差异。两组的 GLP1 曲线下面积都没有增加。接受 FMT 的患者与肥胖相关的微生物群持续向供体转移（P < .001）。接受 FMT 的患者粪便中牛磺胆酸水平持续降低（P < .05) 与基线相比；胆汁酸谱开始与供体更相似。在第 12 周，我们没有观察到任何一组的平均 BMI 有显着变化。结论 在一项安慰剂对照的试点研究中，我们发现 FMT 胶囊（来自瘦肉供体）是安全的，但不会降低代谢未受损的肥胖患者的 BMI。FMT 胶囊具有良好的耐受性，并导致肠道微生物组和胆汁酸谱的持续变化，与瘦肉供体相似。ClinicalTrials.gov 编号：NCT02741518。我们发现 FMT 胶囊（来自瘦肉供体）是安全的，但不会降低代谢未受损的肥胖患者的 BMI。FMT 胶囊具有良好的耐受性，并导致肠道微生物组和胆汁酸谱的持续变化，与瘦肉供体相似。ClinicalTrials.gov 编号：NCT02741518。我们发现 FMT 胶囊（来自瘦肉供体）是安全的，但不会降低代谢未受损的肥胖患者的 BMI。FMT 胶囊具有良好的耐受性，并导致肠道微生物组和胆汁酸谱的持续变化，与瘦肉供体相似。ClinicalTrials.gov 编号：NCT02741518。