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Baseline colitogenicity and acute perturbations of gut microbiota in immunotherapy-related colitis

2024; Rockefeller University Press; Volume: 222; Issue: 1 Linguagem: Inglês

10.1084/jem.20232079

1540-9538

Joan Shang, Diane M. Del Valle, Graham J. Britton, K Mead, Urvija Rajpal, Alice Chen-Liaw, Ilaria Mogno, Z Li, Rajita Menon, Edgar Gonzalez‐Kozlova, Arielle Elkrief, Jonathan U. Peled, Tina Ruth Gonsalves, Neil J. Shah, Michael A. Postow, Jean‐Frédéric Colombel, Sacha Gnjatic, David Faleck, Jeremiah J. Faith,

Clostridium difficile and Clostridium perfringens research

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.