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粪便微生物群移植通过下调黏膜和血清中的促炎细胞因子来改善活动性溃疡性结肠炎。

Fecal Microbiota Transplantation Ameliorates Active Ulcerative Colitis by Downregulating Pro-inflammatory Cytokines in Mucosa and Serum.

作者信息

Zhang Wen-Hui, Jin Ze-Yu, Yang Zhong-Hua, Zhang Jia-Yi, Ma Xiao-Han, Guan Jing, Sun Bao-Lin, Chen Xi

机构信息

Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

USTC-IAT and Chorain Health Joint Laboratory for Human Microbiome, Institute of Advanced Technology, University of Science and Technology of China, Hefei, China.

出版信息

Front Microbiol. 2022 Apr 4;13:818111. doi: 10.3389/fmicb.2022.818111. eCollection 2022.

Abstract

BACKGROUND

Ulcerative colitis (UC) is a multi-factor disease characterized by alternating remission periods and repeated occurrence. It has been shown that fecal microbiota transplantation (FMT) is an emerging and effective approach for UC treatment. Since most existing studies chose adults as donors for fecal microbiota, we conducted this study to determine the long-term efficacy and safety of the microbiota from young UC patient donors and illustrate its specific physiological effects.

METHODS

Thirty active UC patients were enrolled and FMT were administered with the first colonoscopy and two subsequent enema/transendoscopic enteral tubing (TET) practical regimens in The First Affiliated Hospital of Anhui Medical University in China. Disease activity and inflammatory biomarkers were assessed 6 weeks/over 1 year after treatment. The occurrence of adverse events was also recorded. The samples from blood and mucosa were collected to detect the changes of inflammatory biomarkers and cytokines. The composition of gut and oral microbiota were also sampled and sequenced to confirm the alteration of microbial composition.

RESULTS

Twenty-seven patients completed the treatment, among which 16 (59.3%) achieved efficacious clinical response and 11 (40.7%) clinical remission. Full Mayo score and calprotectin dropped significantly and remained stable over 1 year. FMT also significantly reduced the levels of C-reactive protein (CRP), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). The gut microbiota altered significantly with increased bacterial diversity and decreased metabolic diversity in responsive patients. The pro-inflammatory enterobacteria decreased after FMT and the abundance of Collinsella increased. Accordingly, the altered metabolic functions, including antigen synthesis, amino acids metabolism, short chain fatty acid production, and vitamin K synthesis of microbiota, were also corrected by FMT.

CONCLUSION

Fecal microbiota transplantation seems to be safe and effective for active UC patients who are nonresponsive to mesalazine or prednisone in the long-term. FMT could efficiently downregulate pro-inflammatory cytokines to ameliorate the inflammation.

摘要

背景

溃疡性结肠炎(UC)是一种多因素疾病,其特点是缓解期与复发交替出现。已有研究表明,粪便微生物群移植(FMT)是一种新兴且有效的UC治疗方法。由于大多数现有研究选择成年人为粪便微生物群的供体,我们开展了本研究,以确定来自年轻UC患者供体的微生物群的长期疗效和安全性,并阐明其具体生理效应。

方法

在中国安徽医科大学第一附属医院,招募了30例活动期UC患者,并在首次结肠镜检查时以及随后的两次灌肠/经内镜肠内导管(TET)实际治疗方案中进行FMT。在治疗后6周/超过1年评估疾病活动度和炎症生物标志物。还记录了不良事件的发生情况。采集血液和黏膜样本以检测炎症生物标志物和细胞因子的变化。同时对肠道和口腔微生物群的组成进行采样和测序,以确认微生物组成的改变。

结果

27例患者完成治疗,其中16例(59.3%)获得有效临床反应,11例(40.7%)临床缓解。梅奥总评分和钙卫蛋白显著下降,并在1年内保持稳定。FMT还显著降低了C反应蛋白(CRP)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)的水平。反应性患者的肠道微生物群发生显著改变,细菌多样性增加,代谢多样性降低。FMT后促炎肠杆菌减少,柯林斯菌属丰度增加。相应地,微生物群改变的代谢功能,包括抗原合成、氨基酸代谢、短链脂肪酸产生和维生素K合成,也通过FMT得到纠正。

结论

粪便微生物群移植对于长期对美沙拉嗪或泼尼松无反应的活动期UC患者似乎是安全有效的。FMT可有效下调促炎细胞因子以减轻炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf56/9014222/665904f7b9ba/fmicb-13-818111-g001.jpg

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