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

Objective: 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. Methods: 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. Results: 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 P> 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 (F=16.910, P<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 (F=5.255, P=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 (F=10.383, P=0.001). The differences of acetic acid and propionic acid among three groups were not statistically significant (all P>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, P=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, P=0.027). Comparing the incidences of other types of complications, no statistically significant differences were found (all P>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 (P>0.05); there was a positive correlation trend in IBD, IBS and autism, but the differences were not statistically significant (all P>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 P<0.05). Conclusions: 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.目的： 探讨菌群移植（FMT）受体与供体选择的关系，以及不同有效率供体间肠道菌群及代谢产物的特征。 方法： 采用回顾性病例对照研究方法，收集同济大学附属第十人民医院肠道微生态诊疗中心2018年10月至2019年12月期间，治疗病例数≥30例的粪便捐献者（供体）的资料。收集每位供体对应受体（患者）的FMT治疗后随访8周的疗效，依据每位供体的疗效，将供体分为高效组（有效率>60%，10例）、中效组（有效率30%~60%，6例）和低效组（有效率<30%，4例）3组，检测并比较每组供体菌群结构及粪便短链脂肪酸的含量，分析每组供体疗效与并发症发生率，以及供体与受体疗效的关系。FMT疗效的评价指标包括客观临床有效和（或）主观有效，客观有效=临床治愈+临床改善，主观有效指通过问卷随访为显效+中等疗效。 结果： 全组20名供体，共治疗病例总数为1 387例，治疗病种包括慢性便秘749例，慢性腹泻141例，炎性肠病（IBD）107例，肠易激综合征（IBS）121例，自闭症83例，其他疾病包括放射性肠损伤、假性肠梗阻、麻痹性肠梗阻、功能性腹胀和过敏性疾病等共186例。高效组、中效组及低效组分别治疗829例、403例及155例患者，3组治疗患者基线资料的比较，差异均无统计学意义（均P>0.05）。不同有效率供体组间菌群丰度（OTU）的比较，高效组最高（330.68±57.28），中效组次之（237.79±41.89），低效组OTU最低（160.60±49.61）；差异有统计学意义（F=16.910，P<0.001）。菌群多样性（Shannon指数）的比较，高效组和中效组最高（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）。3组间丁酸含量的比较，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OTU最低[（37.23±5.03）μmol/g]；差异有统计学意义（F=10.383，P=0.001）。而乙酸和丙酸3组间差异均无统计学意义（均P>0.05）。全组1 387例患者行FMT治疗，总体不良反应事件418例（30.1%）。低效组、中效组及高效组不良反应发生率分别为40.6%（63/155）、30.0%（121/403）及28.2%（243/829），差异具有统计学意义（χ(2)=9.568，P=0.008）。低效组、中效组及高效组腹泻发生率分别为7.1%（11/155）、4.0%（16/403）及2.8%（23/829），差异具有统计学意义（χ(2)=7.239，P=0.027）。其余各类不良反应发生率的比较，差异均无统计学意义（均P>0.05）。FMT治疗结束8周后进行随访，总随访率为83.6%（1 160/1 387），总有效率为58.3%（676/1 160）。各类疾病的有效率分别：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）。3组间在治疗慢性腹泻的疗效差异无统计学意义（均P>0.05）；治疗IBD、IBS和自闭症有效率与供体疗效存在正相关趋势，但差异未达到统计学意义（均P>0.05）。在治疗慢性便秘和其他疾病上，高效组的治疗有效率最高[分别为65.0%（243/374）和63.2%（55/87）]，中效组次之[分别为49.4%（86/174）和38.1%（16/42）]，而低效组最差[16.1%（9/56）]，差异均有统计学意义（均P<0.05）。 结论： 不同供体对不同疾病有效率存在差异，慢性便秘、放射性肠损伤等需要选择供体疗效较高的供体，IBD、IBS和自闭症的疗效也可能与供体有效性有关，而慢性腹泻症疗效与供体无关。供体有效率与并发症的发生率成负相关，肠道菌群丰度和多样性及丁酸含量可能影响供体的疗效。.