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[粪便微生物群移植受者的临床疗效与供体选择之间的关联]

[Association between the clinical efficacy of fecal microbiota transplantation in recipients and the choice of donor].

作者信息

Chen Q Y, Yang B, Tian H L, Lin Z L, Zhao D, Ye C, Zhang X Y, Qin H L, Li N

机构信息

Department of Colorectal Disease Specialty, Intestinal Microecology Diagnosis and Treatment Center, the Tenth People's Hospital, Tongji University, Shanghai 200072, China.

Department of Colorectal Disease Specialty, Intestinal Microecology Diagnosis and Treatment Center, the Tenth People's Hospital, Tongji University, Shanghai 200072, China; Institute of Intestinal Diseases, Tongji University, Shanghai 200072, China.

出版信息

Zhonghua Wei Chang Wai Ke Za Zhi. 2020 Jul 10;23(Z1):69-76. doi: 10.3760/cma.j.cn.441530-20200417-00222.

DOI:10.3760/cma.j.cn.441530-20200417-00222
PMID:32594729
Abstract

To examine the association between the clinical efficacy of fecal microbiota transplantation (FMT) in recipients and the choice of donor, and to observe the characteristics of intestinal flora and metabolites among different donors. A retrospective case-control study was conducted. Donor whose feces was administrated for more than 30 recipients was enrolled. Data of 20 FMT donors and corresponding recipients at Intestinal Microecology Diagnosis and Treatment Center of the Tenth People's Hospital from October 2018 to December 2019 were collected retrospectively. During follow-up, the efficacy of each recipient 8-week after FMT treatment was recorded and analyzed. Based on the efficacy of each donor, the donors were divided into three groups: high efficacy group (effective rate >60%, 10 donors), moderate efficacy group (effective rate 30%-60%, 6 donors) and low efficacy group (effective rate <30%, 4 donors). The structure of the bacterial flora and the content of fecal short-chain fatty acids in each group of donors were detected and compared among groups. Association of the efficacy of each donor group with the morbidity of complications, and association of efficacy of recipients with donors were analyzed. The evaluation indicators of FMT efficacy included objective clinical effectiveness and/or subjective effectiveness. Objective effectiveness indicated clinical cure plus clinical improvement, and subjective effectiveness indicated marked effectiveness plus medium effectiveness through questionnaire during follow-up. A total of 1387 recipients were treated by 20 donors, including 749 cases of chronic constipation, 141 cases of chronic diarrhea, 107 cases of inflammatory bowel disease (IBD), 121 cases of irritable bowel syndrome (IBS), 83 cases of autism, and 186 cases of other diseases, such as radiation bowel injury, intestinal pseudo-obstruction, paralytic intestinal obstruction, functional bloating and allergic diseases. There were 829 cases, 403 cases, and 155 cases in high efficacy group, moderate efficacy group and low efficacy group respectively. Baseline data among 3 groups were not significantly different (all > 0.05). In comparison of bacterial abundance (operational taxonomic unit, OTU) among different effective donor groups, the high efficacy group was the highest (330.68±57.28), the moderate efficacy group was the second (237.79±41.89), and the low efficacy group was the lowest (160.60±49.61), whose difference was statistically significant (=16.910, <0.001). In comparison of bacterial diversity (Shannon index), the high efficacy group and the moderate efficacy group were higher (2.96±0.36 and 2.67±0.54, respectively), and the low efficacy group was lower (2.09±0.55), whose difference was statistically significant (=5.255, =0.017). In comparison of butyric acid content among three groups, the high efficacy group had the highest [(59.20±9.00) μmol/g], followed by middle efficacy group [(46.92±9.48) μmol/g], and the low efficacy group had the lowest [(37.23±5.03) μmol/g], whose difference was statistically significant (=10.383, =0.001). The differences of acetic acid and propionic acid among three groups were not statistically significant (all >0.05). A total of 418 cases developed complications (30.1%). Morbidity of complication in low efficacy group, moderate efficacy group and high efficacy group was 40.6% (63/155), 30.0% (121/403) and 28.2% (243/829) respectively, and the difference was statistically significant (χ(2)=9.568, =0.008). The incidence of diarrhea in low efficacy group, moderate efficacy group and high efficacy group was 7.1% (11/155), 4.0% (16/403) and 2.8% (23/829) respectively, and the difference was statistically significant (χ(2)=7.239, =0.027). Comparing the incidences of other types of complications, no statistically significant differences were found (all >0.05). Follow up began 8 weeks after the FMT treatment. The total follow-up rate was 83.6% (1160/1387). The overall effective rate 58.3% (676/1160). Effective rates of various diseases were as follows: chronic constipation 54.3% (328/604), chronic diarrhea 88.5% (115/130), IBD 56.1% (55/98), IBS 55.1% (59/107), autism 61.6% (45/73), and other diseases 50.0% (74/148). Comparing the effective rate of three groups of donors for different diseases, there was no statistically significant difference in chronic diarrhea (>0.05); there was a positive correlation trend in IBD, IBS and autism, but the differences were not statistically significant (all >0.05). For chronic constipation and other diseases, high efficacy group had the highest effective rate [65.0% (243/374) and 63.2% (55/87)], followed by moderate efficacy group [49.4% (86/174) and 38.1% (16/42)], and low efficacy group had the lowest [16.1% (9/56) and 15.8% (3/19)], whose differences were significant (all <0.05). Different donors have different efficacy in different diseases. Chronic constipation, radiation bowel injury, etc. need to choose donors with high efficacy. IBD, IBS and autism may also be related to the effectiveness of donors, while chronic diarrhea is not associated to the donor. The efficiency of the donor is negatively correlated to the morbidity of complications. The abundance and diversity of intestinal flora and the content of butyric acid may affect the efficacy of the donor.

摘要

探讨粪便微生物群移植(FMT)受者临床疗效与供体选择之间的关联,并观察不同供体肠道菌群及代谢产物特征。进行一项回顾性病例对照研究。纳入粪便用于30名以上受者的供体。回顾性收集2018年10月至2019年12月在上海市第十人民医院肠道微生态诊疗中心接受FMT的20名供体及其相应受者的数据。随访期间,记录并分析每位受者FMT治疗8周后的疗效。根据每位供体的疗效,将供体分为三组:高效组(有效率>60%,10名供体)、中效组(有效率30%-60%,6名供体)和低效组(有效率<30%,4名供体)。检测并比较各组供体的细菌菌群结构及粪便短链脂肪酸含量。分析各供体组疗效与并发症发生率的关联以及受者疗效与供体的关联。FMT疗效评估指标包括客观临床疗效和/或主观疗效。客观疗效指临床治愈加临床改善,主观疗效指随访期间通过问卷评估的显效加中效。20名供体共治疗1387名受者,其中慢性便秘749例、慢性腹泻141例、炎症性肠病(IBD)107例、肠易激综合征(IBS)121例、自闭症83例、其他疾病(如放射性肠损伤、肠假性梗阻、麻痹性肠梗阻、功能性腹胀及过敏性疾病)186例。高效组、中效组和低效组分别有829例、403例和155例。三组间基线数据差异无统计学意义(均>0.05)。不同有效供体组间细菌丰度(可操作分类单元,OTU)比较,高效组最高(330.68±57.28),中效组次之(237.79±41.89),低效组最低(160.60±49.61),差异有统计学意义(F=16.910,P<0.001)。细菌多样性(香农指数)比较,高效组和中效组较高(分别为2.96±0.36和2.67±0.54),低效组较低(2.09±0.55),差异有统计学意义(F=5.255,P=0.017)。三组间丁酸含量比较,高效组最高[(59.20±9.00)μmol/g],中效组次之[(46.92±9.48)μmol/g],低效组最低[(37.23±5.03)μmol/g],差异有统计学意义(F=10.383,P=0.001)。三组间乙酸和丙酸差异无统计学意义(均>0.05)。共418例发生并发症(30.1%)。低效组、中效组和高效组并发症发生率分别为40.6%(63/155)、30.0%(121/403)和28.2%(243/829),差异有统计学意义(χ²=9.568,P=0.008)。低效组、中效组和高效组腹泻发生率分别为7.1%(11/155)、4.0%(16/403)和2.8%(23/829),差异有统计学意义(χ²=7.239,P=0.027)。比较其他类型并发症发生率,差异无统计学意义(均>0.05)。FMT治疗8周后开始随访。总随访率为83.6%(1160/1387)。总有效率为58.3%(676/1160)。各疾病有效率如下:慢性便秘54.3%(328/604)、慢性腹泻88.5%(115/130)、IBD 56.1%(55/98)、IBS 55.1%(59/107)、自闭症61.6%(45/73)、其他疾病50.0%(74/148)。比较三组供体对不同疾病的有效率,慢性腹泻差异无统计学意义(P>0.05);IBD、IBS和自闭症有正相关趋势,但差异无统计学意义(均>0.05)。慢性便秘和其他疾病,高效组有效率最高[65.0%(243/374)和63.2%(55/87)],中效组次之[49.4%(86/174)和38.1%(16/42)],低效组最低[16.1%(9/56)和15.8%(3/19)],差异有统计学意义(均<0.05)。不同供体对不同疾病疗效不同。慢性便秘、放射性肠损伤等需选择高效供体。IBD、IBS和自闭症可能也与供体有效性有关,而慢性腹泻与供体无关。供体有效性与并发症发生率呈负相关。肠道菌群的丰度、多样性及丁酸含量可能影响供体疗效。

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