粪便细菌疗法
医学
免疫系统
炎症性肠病
内科学
耐火材料(行星科学)
结肠炎
免疫学
移植
微生物群
免疫检查点
癌症研究
微生物学
免疫疗法
艰难梭菌
抗生素
生物
疾病
生物信息学
天体生物学
作者
Taylor Halsey,Anusha Shirwaikar Thomas,Tomo Hayase,Weijie Ma,Hamzah Abu-Sbeih,Baohua Sun,Edwin R. Parra,Zhi‐Dong Jiang,Herbert L. DuPont,Christopher A. Sanchez,Rawan K. El-Himri,Alexandria Brown,Ivonne Flores,Lauren McDaniel,Miriam Ortega Turrubiates,Manfred Hensel,Dung Pham,Stephanie S. Watowich,Eiko Hayase,Chia‐Chi Chang,Robert R. Jenq,Yinghong Wang
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2023-06-14
卷期号:15 (700)
被引量:10
标识
DOI:10.1126/scitranslmed.abq4006
摘要
Immune checkpoint inhibitors (ICIs) target advanced malignancies with high efficacy but also predispose patients to immune-related adverse events like immune-mediated colitis (IMC). Given the association between gut bacteria with response to ICI therapy and subsequent IMC, fecal microbiota transplantation (FMT) represents a feasible way to manipulate microbial composition in patients, with a potential benefit for IMC. Here, we present a large case series of 12 patients with refractory IMC who underwent FMT from healthy donors as salvage therapy. All 12 patients had grade 3 or 4 ICI-related diarrhea or colitis that failed to respond to standard first-line (corticosteroids) and second-line immunosuppression (infliximab or vedolizumab). Ten patients (83%) achieved symptom improvement after FMT, and three patients (25%) required repeat FMT, two of whom had no subsequent response. At the end of the study, 92% achieved IMC clinical remission. 16 S rRNA sequencing of patient stool samples revealed that compositional differences between FMT donors and patients with IMC before FMT were associated with a complete response after FMT. Comparison of pre- and post-FMT stool samples in patients with complete responses showed significant increases in alpha diversity and increases in the abundances of Collinsella and Bifidobacterium , which were depleted in FMT responders before FMT. Histologically evaluable complete response patients also had decreases in select immune cells , including CD8 + T cells, in the colon after FMT when compared with non-complete response patients ( n = 4). This study validates FMT as an effective treatment strategy for IMC and gives insights into the microbial signatures that may play a critical role in FMT response.
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