Immune-related colitis is associated with fecal microbial dysbiosis and can be mitigated by fecal microbiota transplantation Journal Article
| Authors: | Elkrief, A.; Waters, N. R.; Smith, N.; Dai, A.; Slingerland, J.; Aleynick, N.; Febles, B.; Gogia, P.; Socci, N. D.; Lumish, M.; Giardina, P. A.; Chaft, J. E.; Eng, J.; Motzer, R. J.; Mendelsohn, R. B.; Markey, K. A.; Zhuang, M.; Li, Y.; Yang, Z.; Hollmann, T. J.; Rudin, C. M.; van den Brink, M. R. M.; Shia, J.; DeWolf, S.; Schoenfeld, A. J.; Hellmann, M. D.; Babady, N. E.; Faleck, D. M.; Peled, J. U. |
| Article Title: | Immune-related colitis is associated with fecal microbial dysbiosis and can be mitigated by fecal microbiota transplantation |
| 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 a-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. |
| Keywords: | treatment outcome; prospective study; prospective studies; colitis; intestine flora; biological product; biological products; complication; humans; human; fecal microbiota transplantation; dysbiosis; gastrointestinal microbiome |
| Journal Title: | Cancer Immunology Research |
| Volume: | 12 |
| Issue: | 3 |
| ISSN: | 2326-6066 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2024-03-01 |
| Start Page: | 308 |
| End Page: | 321 |
| Language: | English |
| DOI: | 10.1158/2326-6066.Cir-23-0498 |
| PUBMED: | 38108398 |
| PROVIDER: | scopus |
| PMCID: | PMC10932930 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK authors: Jonathan U. Peled -- Source: Scopus |
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