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

Autor:	Elkrief A; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.; Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Waters NR; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York., Smith N; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York., Dai A; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York., Slingerland J; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York., Aleynick N; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York., Febles B; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York., Gogia P; Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Socci ND; Bioinformatics Core Facility, Memorial Sloan Kettering Cancer Center, New York, New York.; Marie-Josée & Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York., Lumish M; Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Giardina PA; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York., Chaft JE; Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Cornell Medical College, New York, New York., Eng J; Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Cornell Medical College, New York, New York., Motzer RJ; Weill Cornell Medical College, New York, New York.; Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Mendelsohn RB; Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Cornell Medical College, New York, New York., Markey KA; Fred Hutchinson Cancer Center, Seattle, Washington.; Division of Medical Oncology, University of Washington, Seattle, Washington., Zhuang M; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York., Li Y; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York., Yang Z; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York., Hollmann TJ; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Bristol Myers Squibb, Princeton, New Jersey., Rudin CM; Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Cornell Medical College, New York, New York., van den Brink MRM; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Cornell Medical College, New York, New York.; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Shia J; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., DeWolf S; Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Schoenfeld AJ; Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Cornell Medical College, New York, New York., Hellmann MD; Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Cornell Medical College, New York, New York., Babady NE; Clinical Microbiology Service, Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Infectious Disease Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Faleck DM; Weill Cornell Medical College, New York, New York.; Gastroenterology, Hepatology and Nutrition Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Peled JU; Weill Cornell Medical College, New York, New York.; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Jazyk:	angličtina
Zdroj:	Cancer immunology research [Cancer Immunol Res] 2024 Mar 04; Vol. 12 (3), pp. 308-321.
DOI:	10.1158/2326-6066.CIR-23-0498
Abstrakt:	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. (©2023 American Association for Cancer Research.)
Databáze:	MEDLINE
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