Effects of Fecal Microbiota Transplantation With Oral Capsules in Obese Patients

Effects of Fecal Microbiota Transplantation With Oral Capsules in Obese Patients
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DOI:
10.1016/j.cgh.2019.07.006
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发表时间:
2020-04-01
影响因子:
12.6
通讯作者:
Thompson, Christopher
Thompson, Christopher
中科院分区:
医学1区
文献类型:
--
作者:
Allegretti, Jessica R.;Kassam, Zain;Thompson, Christopher

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背景与目的:对小鼠的研究表明,肠道微生物区系可通过厌食性胃肠激素胰高血糖素样肽1(GLP1)和胆汁酸影响脂代谢而导致肥胖。我们进行了一项随机、安慰剂对照的初步研究,研究了粪便微生物区系移植(FMT)对代谢正常的肥胖患者的影响。方法:我们对22名肥胖患者(体重指数[BMI]和Gt;=5 kg/m(2))进行了双盲研究,这些患者没有糖尿病、非酒精性脂肪性肝炎或代谢综合征的诊断。参与者被随机(1:1)分配到接受FMT的胶囊组(第4周诱导剂量为30粒,第8周维持剂量为12粒)或安慰剂胶囊。FMT胶囊来源于单一瘦肉供体(BMI,17.5 kg/m(2))。对患者进行了26周的随访,主要结果是安全。患者在服用第一剂FMT或安慰剂后的第1、4、6、8和12周采集粪便和血清样本,并进行16S RNA基因测序分析。采用液-质联用技术对粪便和血清样品进行代谢组学分析。其他结果是12周时GLP1曲线下面积的变化。结果:我们观察到接受FMT和安慰剂的患者在不良事件方面没有显著差异。两组GLP1曲线下面积均未见增加。接受FMT的患者与肥胖相关的微生物群持续向供者转移(P
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/m(2)) 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/m(2)). 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