A Randomized Clinical Trial of Fecal Microbiota Transplant for Alcohol Use Disorder
A Randomized Clinical Trial of Fecal Microbiota Transplant for Alcohol Use Disorder
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DOI：
10.1002/hep.31496
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发表时间：
2021-03-16
期刊：
影响因子：
13.5
通讯作者：
Gillevet, Patrick M.
中科院分区：
文献类型：
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作者：
Bajaj, Jasmohan S.;Gavis, Edith A.;Gillevet, Patrick M.
背景和目的酒精使用障碍（AUD）与肝硬化恶化的微生物改变有关。方法和结果在该1期、双盲、随机临床试验中，患有AUD相关肝硬化的饮酒问题（AUDIT-10 > 8）的患者以1：1的比例随机接受来自富含毛螺菌科和瘤胃球菌科的供体的安慰剂或FMT灌肠剂。6个月的安全性是主要结局。在基线和第15天测试了酒精渴求问卷、酒精消耗量（尿乙基葡萄糖醛酸苷/肌酐）、生活质量、认知、血清IL-6和脂多糖结合蛋白、血浆/粪便短链脂肪酸（SCFA）和粪便微生物群。进行了6个月随访和严重不良事件（SAE）分析。纳入了20例具有相似人口统计学特征、肝硬化和AUD严重程度的AUD相关肝硬化患者（65 ± 6.4岁，所有男性，终末期肝病模型8.9 ± 2.7）。在第15天，90%的FMT组与30%的安慰剂组相比，渴求显著降低（P = 0.02），尿乙基葡萄糖醛酸苷/肌酐降低（P = 0.03），认知和心理社会生活质量改善。与基线相比，FMT组血清IL-6和脂多糖结合蛋白降低，丁酸/异丁酸升高，但安慰剂组无此现象。微生物多样性随着瘤胃球菌科和其他SCFA的增加而增加，在FMT后产生分类群，但不产生安慰剂，这与SCFA水平有关。6个月时，发生任何SAE的患者（8 vs. 2，P = 0.02），AUD相关SAE（7 vs. 1，P = 0.02）和SAE/患者（中位数[四分位距]，FMT为1.5 [1.25] vs. 0 [0.25]，P = 0.02），安慰剂组高于FMT组。结论这项1期试验表明，FMT是安全的，与短-与安慰剂相比，酒精相关性肝硬化伴酒精滥用患者的酒精渴求和饮酒量长期减少，并出现有利的微生物变化。在分配至FMT组的患者中，6个月内AUD相关事件也减少。
Background and Aims Alcohol use disorder (AUD) is associated with microbial alterations that worsen with cirrhosis. Fecal microbiota transplant (FMT) could be a promising approach.Approach and Results In this phase 1, double-blind, randomized clinical trial, patients with AUD-related cirrhosis with problem drinking (AUDIT-10 > 8) were randomized 1:1 into receiving one placebo or FMT enema from a donor enriched in Lachnospiraceae and Ruminococcaceae. Six-month safety was the primary outcome. Alcohol craving questionnaire, alcohol consumption (urinary ethylglucuronide/creatinine), quality of life, cognition, serum IL-6 and lipopolysaccharide-binding protein, plasma/stool short-chain fatty acids (SCFAs), and stool microbiota were tested at baseline and day 15. A 6-month follow-up with serious adverse event (SAE) analysis was performed. Twenty patients with AUD-related cirrhosis (65 +/- 6.4 years, all men, Model for End-Stage Liver Disease 8.9 +/- 2.7) with similar demographics, cirrhosis, and AUD severity were included. Craving reduced significantly in 90% of FMT versus 30% in placebo at day 15 (P = 0.02) with lower urinary ethylglucuronide/creatinine (P = 0.03) and improved cognition and psychosocial quality of life. There was reduction in serum IL-6 and lipopolysaccharide-binding protein and increased butyrate/isobutyrate compared with baseline in FMT but not placebo. Microbial diversity increased with higher Ruminococcaceae and other SCFAs, producing taxa following FMT but not placebo, which were linked with SCFA levels. At 6 months, patients with any SAEs (8 vs. 2, P = 0.02), AUD-related SAEs (7 vs. 1, P = 0.02), and SAEs/patient (median [interquartile range], 1.5 [1.25] vs. 0 [0.25] in FMT, P = 0.02) were higher in placebo versus FMT.Conclusions This phase 1 trial shows that FMT is safe and associated with short-term reduction in alcohol craving and consumption with favorable microbial changes versus placebo in patients with alcohol-associated cirrhosis with alcohol misuse. There was also a reduction in AUD-related events over 6 months in patients assigned to FMT.