TY - JOUR
T1 - Baseline colitogenicity and acute perturbations of gut microbiota in immunotherapy-related colitis
AU - Shang, Joan
AU - Del Valle, Diane Marie
AU - Britton, Graham J.
AU - Mead, K. R.
AU - Rajpal, Urvija
AU - Chen-Liaw, Alice
AU - Mogno, Ilaria
AU - Li, Zhihua
AU - Menon, Rajita
AU - Gonzalez-Kozlova, Edgar
AU - Elkrief, Arielle
AU - Peled, Jonathan U.
AU - Gonsalves, Tina Ruth
AU - Shah, Neil J.
AU - Postow, Michael
AU - Colombel, Jean Frederic
AU - Gnjatic, Sacha
AU - Faleck, David M.
AU - Faith, Jeremiah J.
N1 - Publisher Copyright:
© 2024 Shang et al.
PY - 2025/1/6
Y1 - 2025/1/6
N2 - 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 ICItreated 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.
AB - 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 ICItreated 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.
UR - http://www.scopus.com/inward/record.url?scp=85212459824&partnerID=8YFLogxK
U2 - 10.1084/jem.20232079
DO - 10.1084/jem.20232079
M3 - Article
C2 - 39666007
AN - SCOPUS:85212459824
SN - 0022-1007
VL - 222
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 1
M1 - e20232079
ER -