Changes in the composition of the intestinal microbiota, associated with IL-6 deficiency

Abstract

Interleukin-6 (IL-6) is a broad-spectrum cytokine involved in the immune, nervous, and endocrine regulation of many biological processes. IL-6 performs both homeostatic and pathogenic functions. It is one of the key factors in the cytokine storm in COVID-19, and it also controls the production of acute phase proteins during inflammation. IL-6 is involved in the maintenance of intestinal homeostasis and is required for both the induction of inflammation and the repair of the injured intestinal tissue. In turn, the commensal microbiota, represented by eukaryotes, prokaryotes, and viruses, is one of the key factors modulating the immune response in the gut. The predominance of certain groups of commensal microorganisms is associated with the development of intestinal inflammation, while probiotics and antibiotics are successfully used to control inflammatory bowel disease. IL-6 is also necessary to maintain the barrier function of the intestine by modulating the proliferation of intestinal cells, which is necessary for their timely renewal both in homeostasis and inflammation. It has been established that the genetic inactivation of IL6 contributes to the development of intestinal inflammation, while the involvement of IL-6 in the control of the gut microbiota composition remains unclear. To investigate this issue, we analyzed stool samples from wild-type naive mice and mice deficient in IL6 (IL-6 KO) generated on the C57Bl/6 genetic background. It has been determined that IL-6 KO shows significant changes in some taxonomic groups of commensals, which may explain the sensitivity of IL-6 KO to the development of colitis. Interestingly, the relative contents of Firmicutes and Clostridiales are significantly reduced, whereas Bacteroides are increased in IL-6 KO as compared with wild-type mice. Our data on the reduction of Firmicutes, Lactobacillaceae, and other large taxa in IL-6 deficient mice suggest that the microbiota composition of IL-6 KO mice is somewhat similar to that of mice with chronic intestinal inflammation. Our study serves as a perspective for further research on the contribution of IL-6-mediated changes in the microbiota composition to the maintenance of intestinal homeostasis and the development of chronic gut inflammation.