Immune-Related Colitis Is Associated with Fecal Microbial Dysbiosis and Can Be Mitigated by Fecal Microbiota Transplantation

失调 粪便细菌疗法 微生物群 医学 粪便 背景(考古学) 肠道菌群 结肠炎 免疫学 移植 内科学 炎症性肠病 胃肠病学 抗生素 艰难梭菌 疾病 生物 微生物学 生物信息学 古生物学
作者
Arielle Elkrief,Nicholas R. Waters,Natalie Smith,Anqi Dai,John Slingerland,Nathan Aleynick,Binita Febles,Pooja Gogia,Nicholas D. Socci,Melissa Lumish,Paul A. Giardina,Jamie E. Chaft,Juliana Eng,Robert J. Motzer,Robin B. Mendelsohn,Kate A. Markey,Mingqiang Zhuang,Yanyun Li,Zhifan Yang,Travis J. Hollmann,Charles M. Rudin,Marcel R.M. van den Brink,Jinru Shia,Susan DeWolf,Adam J. Schoenfeld,Matthew D. Hellmann,N. Esther Babady,David M. Faleck,Jonathan U. Peled
出处
期刊:Cancer immunology research [American Association for Cancer Research]
卷期号:12 (3): 308-321 被引量:4
标识
DOI:10.1158/2326-6066.cir-23-0498
摘要

Abstract Colitis induced by treatment with immune-checkpoint inhibitors (ICI), termed irColitis, is a substantial cause of morbidity complicating cancer treatment. We hypothesized that abnormal fecal microbiome features would be present at the time of irColitis onset and that restoring the microbiome with fecal transplant from a healthy donor would mitigate disease severity. Herein, we present fecal microbiota profiles from 18 patients with irColitis from a single center, 5 of whom were treated with healthy-donor fecal microbial transplantation (FMT). Although fecal samples collected at onset of irColitis had comparable α-diversity to that of comparator groups with gastrointestinal symptoms, irColitis was characterized by fecal microbial dysbiosis. Abundances of Proteobacteria were associated with irColitis in multivariable analyses. Five patients with irColitis refractory to steroids and biologic anti-inflammatory agents received healthy-donor FMT, with initial clinical improvement in irColitis symptoms observed in four of five patients. Two subsequently exhibited recurrence of irColitis symptoms following courses of antibiotics. Both received a second “salvage” FMT that was, again, followed by clinical improvement of irColitis. In summary, we observed distinct microbial community changes that were present at the time of irColitis onset. FMT was followed by clinical improvements in several cases of steroid- and biologic-agent-refractory irColitis. Strategies to restore or prevent microbiome dysbiosis in the context of immunotherapy toxicities should be further explored in prospective clinical trials.
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