ИСТИНА

IL-6 is known to promote gut carcinogenesis and to support epithelial barrier function during colitis. The gut microbiome is a crucial factor for shaping immune responses. Accumulating evidence suggests that IL-6 may regulate intestinal homeostasis via modulation of gut microbiota. To test this hypothesis, we studied susceptibility of IL-6 knockout (IL-6 KO) mice to tumor development in the model of AOM/DSS-induced colorectal cancer under separate housing and cohousing conditions. We found that housing conditions do not affect intestinal inflammation in the acute DSS-induced colitis model. However, in AOM/DSS-induced colorectal cancer model separately housed IL-6 KO mice showed a reduced number of tumors as compared to wild type controls, whereas no difference in tumor development was observed between cohoused IL-6-deficient and wild type mice. Similarly, IL-6 KO mice suffered from increased body weight loss during chronic intestinal inflammation induced by DSS under separate housing, but not cohousing conditions. Interestingly, the abundance of Enterobacteriaceae family was significantly higher in the feces of naïve IL-6-deficient mice cohoused with wild type mice, which did not occur during separate housing. Moreover, aged IL-6 KO mice demonstrated an increased level of commensal segmented filamentous bacteria in the ileum as compared to cohoused wild type controls. These results indicate that IL-6 plays an essential role in maintaining gut microbiota composition, and its disturbance may result in the altered susceptibility to intestinal carcinogenesis. Altogether, our data suggest that IL-6 can promote intestinal tumor progression by modulating gut microbiota.