Akkermansia muciniphila ameliorates Salmonella-induced colitis and intestinal fibrosis.

Abstract

Salmonella enterica serovar Typhimurium is a food-borne pathogen and a major cause of gastroenteritis in humans. The intestinal microbiota provides colonization resistance to enteric pathogens such as S. Typhimurium. Akkermansia muciniphila is an anaerobic bacterium commonly found in the intestinal tract of humans and other mammals and specializes in the degradation of mucin. To study the role of A. muciniphila in affecting the outcome of S. Typhimurium colonization and pathology, we used gnotobiotic mice colonized with a defined simplified human (SIHUMI) or mouse (OMM¹¹) intestinal microbiota and infected them with the attenuated S. Typhimurium ΔaroA strain. By comparing SIHUMI and OMM¹¹ mice to mice additionally colonized with A. muciniphila, we demonstrate that the presence of A. muciniphila leads to a decrease in intestinal Salmonella colonization. In addition, Salmonella-induced colitis is significantly reduced in the presence of A. muciniphila including improved histopathological changes as well as decreased levels of inflammatory cytokines. Furthermore, we demonstrate that viable A. muciniphila inhibit adhesion of Salmonella to the intestinal epithelium in vivo as well as to differentiated, polarized HT29-MTX-E12 epithelial cells. These data indicate that A. muciniphila plays an important role in mediating protection from S. Typhimurium colitis by inhibiting adhesion of Salmonella to the intestinal epithelium.