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经结肠镜检查的粪便微生物移植对严重肥胖和胰岛素抵抗患者的影响:一项随机、双盲、安慰剂对照的 2 期临床试验。

Effect of faecal microbial transplant via colonoscopy in patients with severe obesity and insulin resistance: A randomized double-blind, placebo-controlled Phase 2 trial.

机构信息

Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.

Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.

出版信息

Diabetes Obes Metab. 2023 Feb;25(2):479-490. doi: 10.1111/dom.14891. Epub 2022 Oct 28.

DOI:10.1111/dom.14891
PMID:36239189
Abstract

AIM

To assess the effects of faecal microbial transplant (FMT) from lean people to subjects with obesity via colonoscopy.

MATERIAL AND METHODS

In a double-blind, randomized controlled trial, subjects with a body mass index ≥ 35 kg/m and insulin resistance were randomized, in a 1:1 ratio in blocks of four, to either allogenic (from healthy lean donor; n = 15) or autologous FMT (their own stool; n = 13) delivered in the caecum and were followed for 3 months. The main outcome was homeostatic model assessment of insulin resistance (HOMA-IR) and secondary outcomes were glycated haemoglobin levels, lipid profile, weight, gut hormones, endotoxin, appetite measures, intestinal microbiome (IM), metagenome, serum/faecal metabolites, quality of life, anxiety and depression scores.

RESULTS

In the allogenic versus autologous groups, HOMA-IR and clinical variables did not change significantly, but IM and metabolites changed favourably (P < 0.05): at 1 month, Coprococcus, Bifidobacterium, Bacteroides and Roseburia increased, and Streptococcus decreased; at 3 months, Bacteroides and Blautia increased. Several species also changed significantly. For metabolites, at 1 month, serum kynurenine decreased and faecal indole acetic acid and butenylcarnitine increased, while at 3 months, serum isoleucine, leucine, decenoylcarnitine and faecal phenylacetic acid decreased. Metagenomic pathway representations and network analyses assessing relationships with clinical variables, metabolites and IM were significantly enhanced in the allogenic versus autologous groups. LDL and appetite measures improved in the allogenic (P < 0.05) but not in the autologous group.

CONCLUSIONS

Overall, in those with obeisty, allogenic FMT via colonoscopy induced favourable changes in IM, metabolites, pathway representations and networks even though other metabolic variables did not change. LDL and appetite variables may also benefit.

摘要

目的

通过结肠镜检查评估从瘦人向肥胖受试者移植粪便微生物(FMT)的效果。

材料和方法

在一项双盲、随机对照试验中,将体质指数(BMI)≥35kg/m²且存在胰岛素抵抗的受试者按 1:1 比例分为两组,以 4 人为一组进行随机分组,分别接受异体(来自健康瘦供体;n=15)或自体 FMT(自身粪便;n=13),移植至盲肠,并随访 3 个月。主要结局为稳态模型评估的胰岛素抵抗(HOMA-IR),次要结局为糖化血红蛋白水平、血脂谱、体重、肠道激素、内毒素、食欲测量、肠道微生物组(IM)、宏基因组、血清/粪便代谢物、生活质量、焦虑和抑郁评分。

结果

在异体组与自体组中,HOMA-IR 和临床变量无显著变化,但 IM 和代谢物变化有利(P<0.05):1 个月时,粪肠球菌、双歧杆菌、拟杆菌和罗斯伯里氏菌增加,而链球菌减少;3 个月时,拟杆菌和布劳特氏菌增加。一些物种也有显著变化。对于代谢物,1 个月时血清犬尿氨酸减少,粪便吲哚乙酸和丁烯基肉碱增加,而 3 个月时血清异亮氨酸、亮氨酸、癸烯酰肉碱和粪便苯乙酸减少。评估与临床变量、代谢物和 IM 关系的宏基因组途径表示和网络分析在异体组中显著增强。异体组 LDL 和食欲测量改善(P<0.05),但自体组无改善。

结论

总体而言,在肥胖受试者中,通过结肠镜检查进行异体 FMT 可引起 IM、代谢物、途径表示和网络的有利变化,尽管其他代谢变量没有变化。LDL 和食欲变量也可能受益。

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