Baseline colitogenicity and acute perturbations of gut microbiota in immunotherapy-related colitis Journal Article
| Authors: | Shang, J.; Del Valle, D. M.; Britton, G. J.; Mead, K. R.; Rajpal, U.; Chen-Liaw, A.; Mogno, I.; Li, Z.; Menon, R.; Gonzalez-Kozlova, E.; Elkrief, A.; Peled, J. U.; Gonsalves, T. R.; Shah, N. J.; Postow, M.; Colombel, J. F.; Gnjatic, S.; Faleck, D. M.; Faith, J. J. |
| Article Title: | Baseline colitogenicity and acute perturbations of gut microbiota in immunotherapy-related colitis |
| Abstract: | Immunotherapy-related colitis (irC) frequently emerges as an immune-related adverse event during immune checkpoint inhibitor therapy and is presumably influenced by the gut microbiota. We longitudinally studied microbiomes from 38 ICI-treated cancer patients. We compared 13 ICI-treated subjects who developed irC against 25 ICI-treated subjects who remained irC-free, along with a validation cohort. Leveraging a preclinical mouse model, predisease stools from irC subjects induced greater colitigenicity upon transfer to mice. The microbiota during the first 10 days of irC closely resembled inflammatory bowel disease microbiomes, with reduced diversity, increased Proteobacteria and Veillonella, and decreased Faecalibacterium, which normalized before irC remission. These findings highlight the irC gut microbiota as functionally distinct but phylogenetically similar to non-irC and healthy microbiomes, with the exception of an acute, transient disruption early in irC. We underscore the significance of longitudinal microbiome profiling in developing clinical avenues to detect, monitor, and mitigate irC in ICI therapy cancer patients. © 2024 Shang et al. |
| Keywords: | aged; middle aged; neoplasm; neoplasms; mouse; animal; animals; mice; drug effect; mice, inbred c57bl; c57bl mouse; immunology; immunotherapy; colitis; drug therapy; intestine flora; microbiology; feces; therapy; adverse event; procedures; immune checkpoint inhibitor; humans; human; male; female; immune checkpoint inhibitors; gastrointestinal microbiome |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 222 |
| Issue: | 1 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2025-01-06 |
| Language: | English |
| DOI: | 10.1084/jem.20232079 |
| PUBMED: | 39666007 |
| PROVIDER: | scopus |
| PMCID: | PMC11636624 |
| DOI/URL: | |
| Notes: | PDF lists the publication date as winter -- The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: David M. Faleck -- Source: Scopus |
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