粪菌移植对肠易激综合征临床疗效和肠道菌群影响的非对照初步研究

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目的:探讨粪菌移植治疗IBS的有效性、安全性及其对IBS患者肠道菌群的影响。方法:选择2016年9月至2017年8月在广州市第一人民医院行粪菌移植的IBS住院患者28例。所有IBS患者于粪菌移植前、粪菌移植后4和12周完成肠易激综合征生活质量量表(IBS-QOL)、肠易激综合征严重程度系统评分(IBS-SSS)和胃肠道症状分级(GSRS)评分。IBS患者粪菌移植前和粪菌移植后4周行16S rDNA测序,从门、科、属水平分别分析粪菌移植对IBS患者肠道菌群多样性和菌群结构的影响,进一步应用线性判别分析效应量(LEfSe)筛选差异菌属。采用配对n t检验和配对秩和检验进行统计学分析。n 结果:粪菌移植后12周,IBS-QOL心境恶劣、行为障碍、自体意象、健康担忧、进食逃避和关系拓展6个维度的评分均低于粪菌移植前[分别为43.750分(22.656分,56.250分)比48.438分(32.031分,60.938分)、37.500分(18.750分,56.250分)比46.429分(21.429分,62.500分)、31.250分(14.063分,42.188分)比31.250分(18.750分,50.000分)、41.667分(27.083分,56.250分)比50.000分(41.667分,66.667分)、54.167分(43.750分,72.917分)比66.667分(58.333分,83.333分)、8.333分(0.000分,33.333分)比16.667分(8.333分,33.333分)],差异均有统计学意义(n Z=-2.157、-3.429、-2.274、-3.197、-3.042、-2.329,n P均<0.05)。粪菌移植后12周,IBS-QOL行为障碍和关系拓展2个维度的评分均低于粪菌移植后4周[分别为37.500分(18.750分,56.250分)比39.286分(19.643分,62.500分)和8.333分(0.000分,33.333分)比16.670分(2.083分,41.667分)],差异均有统计学意义(n Z=-1.998、-2.110,n P均<0.05)。粪菌移植后4和12周的IBS-SSS、GSRS评分均低于粪菌移植前[(190.32±106.51)、(201.43±102.48)分比(245.93±86.10)分和5.50分(4.00分,9.00分)、5.50分(4.00分,8.75分)比7.00分(6.00分,9.75分)],差异均有统计学意义(n t=4.402、3.848,n Z=-3.081、-3.609;n P均<0.01)。粪菌移植后患者均无严重不良反应发生。门水平中,粪菌移植后IBS患者粪便中疣微菌门的丰度高于粪菌移植前(6.74%比0.37%);科水平中,粪菌移植后IBS患者粪便中疣微菌科的丰度高于粪菌移植前(6.74%比0.37%);属水平中,粪菌移植后IBS患者粪便中艾克曼菌的丰度高于粪菌移植前(6.74%比0.37%),差异均有统计学意义(n Z均=-2.589,n P均=0.010)。LEfSe法发现,粪菌移植后4周,IBS患者肠道菌群中艾克曼菌的丰度高于粪菌移植前(6.74%比0.37%),差异有统计学意义(线性判别分析值=4.5,n P=0.049)。n 结论:初步证实粪菌移植治疗IBS安全、有效,其作用机制可能是通过上调IBS患者肠道菌群多样性和改变菌群结构发挥疗效。“,”Objective:To investigate the efficacy and safety of fecal microbiota transplantation (FMT) in the treatment of irritable bowel syndrome (IBS), and to explore the effects of FMT on the gut microbiota of IBS patients.Methods:From September 2016 to August 2017, at Guangzhou First People′s Hospital, 28 hospitalized IBS patients who underwent FMT treatment were enrolled. Before FMT, four and 12 weeks after FMT, all the IBS patients completed the irritable bowel syndrome quality of life scale (IBS-QOL), irritable bowel syndrome severity scoring system (IBS-SSS) and gastrointestinal symptom rating scale (GSRS). 16S rDNA sequencing was performed before FMT and four weeks after FMT. The effects of FMT on gut microbiota diversity and microbiota structure of IBS patients were analyzed respectively from the level of phylum, family and genus, and linear discriminant analysis effect size (LEfSe) was further used to screen the different bacteria. Paired n t test and paired rank sum test were used for statistical analysis.n Results:Twelve weeks after FMT, the scores of the six dimensions of IBS-QOL including dysthymia, behavioral disorder, auto imagery, health concerns, eating avoidance, and relationship expansion were all lower than those before FMT (43.750, 22.656 to 56.250 vs. 48.438, 32.031 to 60.938; 37.500, 18.750 to 56.250 vs. 46.429, 21.429 to 62.500; 31.250, 14.063 to 42.188 vs. 31.250, 18.750 to 50.000; 41.667, 27.083 to 56.250 vs. 50.000, 41.667 to 66.667; 54.167, 43.750 to 72.917 vs. 66.667, 58.333 to 83.333; 8.333, 0.000 to 33.333 vs. 16.667, 8.333 to 33.333, respectively), and the differences were statistically significant (n Z=-2.157, -3.429, -2.274, -3.197, -3.042 and -2.329, all n P<0.05). Twelve weeks after FMT, the scores of the two dimensions of IBS-QOL including behavioral disorder and relationship expansion were both lower than those of four weeks after FMT (37.500, 18.750 to 56.250 vs. 39.286, 19.643 to 62.500 and 8.333, 0.000 to 33.333 vs. 16.670, 2.083 to 41.667, respectively), and the differences were statistically significant (n Z=-1.998 and -2.110, both n P<0.05). Four and 12 weeks after FMT, the scores of IBS-SSS and GSRS were both lower than those before FMT ((190.32±106.51), (201.43±102.48) vs. (245.93±86.10) and 5.50, 4.00 to 9.00 and 5.50, 4.00 to 8.75 vs. 7.00, 6.00 to 9.75), and the differences were statistically significant (n t=4.402 and 3.848, n Z=-3.081 and -3.609; all n P<0.01). No serious adverse reactions occurred in the patients after FMT. At the phylum level, after FMT the abundance ofn Verrucomicrobia in the feces of IBS patients was richer than that before FMT (6.74% vs. 0.37%); at the family level, after FMT the abundance of n Verrucomicrobiaceae in the feces of IBS patients was richer than that before FMT (6.74% vs. 0.37%); at the genus level, after FMT the abundance of n Akkermansia was richer than that before FMT (6.74% vs. 0.37%); and the differences were statistically significant (all n Z=-2.589, all n P=0.010). The results of LEfSe method indicated that four weeks after FMT the abundance of n Akkermansia in the gut microbiota of IBS patients was richer than that before FMT (6.74% vs. 0.37%), and the difference was statistically significant (linear discriminant analysis value=4.5, n P=0.049).n Conclusions:FMT is safe and effective in the treatment of IBS. The mechanism may be through upregulating the diversity of gut microbiota and changing the structure of gut microbiota of IBS patients.
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