@phdthesis{Ring2018, author = {Ring, Christiane}, title = {The role of the commensal gut bacterium Akkermansia muciniphila in acute and chronic intestinal inflammation}, year = {2018}, abstract = {Microbiota analyses of patients suffering from various diseases suggest a beneficial role of Akkermansia muciniphila in the maintenance of health, whereas several studies in animal models of intestinal inflammation report that this organism may aggravate inflammation. Therefore, it is important to clarify under which circumstances A. muciniphila exerts negative effects in the intestine of its host. The previously reported observation that A. muciniphila aggravates acute intestinal inflammation in the Salmonella enterica serovar Typhimurium infection mouse model colonized with a simplified human intestinal microbiota was investigated in this study. To unravel the underlying mechanism that led to the observed phenomenon, the time course of events following the infection was analyzed. In mice colonized with a simplified human intestinal microbiota, Salmonella infection induced clear signs of intestinal inflammation three days post infection. The inflammatory response was similar in mice colonized with A. muciniphila before Salmonella infection. These observations were independent of the time when colonization with the simplified human intestinal microbiota occurred, right after birth or only after weaning, and contradict the previous report. To find out whether A. muciniphila influences the development of chronic intestinal inflammation in a genetically predisposed host, mono-associated interleukin-10-deficient (Il10-/-) mice, Il10-/- mice dual-associated with A. muciniphila and colitogenic Escherichia coli NC101, as well as Il10-/- mice associated with A. muciniphila and a simplified human intestinal microbiota were compared to the respective mice without A. muciniphila. The data clearly show that in these gnotobiotic Il10-/- mice, A. muciniphila neither induces intestinal inflammation itself nor modulates it after induction by a colitogenic bacterium or by a simplified human intestinal microbiota. The experiments lead to the conclusion that the promotion of intestinal inflammation is not an intrinsic feature of this bacterium. The results of this study encourage the proposed use of A. muciniphila for the prevention or treatment of metabolic disorders.}, language = {en} }