Durigast_F_prausnitzii_ICI_gastric_adenocarcinoma
The gut microbiota plays a key role in shaping the immune response and has been found to affect responses to immune checkpoint inhibitors (ICIs) in different cancer types, but mostly in melanoma. Enrichment of specific commensal bacteria has been correlated with improved progression-free survival (PFS) and overall survival (OS). Anti–programmed cell death 1 ICIs have recently been approved as a first-line treatment for advanced esophageal and gastric adenocarcinomas in combination with chemotherapy. Although some data showed that antibiotic administration is associated with worse outcomes in patients treated with programmed cell death 1 blockade, data regarding the specific role of some microbiome taxa in this setting are scarce. Here, we took advantage of the DURIGAST study to address ICI efficacy and toxicity. Patients were randomized to receive FOLFIRI (leucovorin calcium [folinic acid], fluorouracil, and irinotecan hydrochloride) plus durvalumab (anti–programmed cell death ligand 1) with or without tremelimumab (anti–cytotoxic T-lymphocyte–associated protein 4). A prospective stools collection was planned with 1 stool sample before treatment (week 0) and 1 at the first evaluation at 8 weeks. As no difference was observed in terms of PFS or OS between the 2 arms, all of the patients were considered together in the current study. Indeed, we analyzed 41 stools before treatment and 20 after 8 weeks of treatment. Overall, 36% of patients had 2 stools or more by day. After treatment by chemotherapy plus ICI, we observed significant changes in gut microbiota composition and function, but not in terms of a-diversity (Shannon's H diversity index P = .112). Notably, Fusobacterium nucleatum, which is involved in the progression of several cancer types, and several other bacterial species usually found in the oral microbiota were increased at 8 weeks after treatment start as compared with baseline (week 0). At the functional level, the strongest signal driving the difference between week 0 and week 8 is the increased “L-lysine fermentation to acetate and butanoate” pathway, which is directly related to F. nucleatum. Moreover, there was no difference in the microbiota according to programmed cell death ligand 1 combined positive score.