Escherichia coli‐derived outer‐membrane vesicles induce immune activation and progression of cirrhosis in mice and humans

• DOI: 10.1111/liv.15539
• Publication Date: 2023-02-08T08:27:59Z
• Authors: Kazuki Natsui; Atsunori Tsuchiya; Risa Imamiya; Mayuko Osada‐Oka; Yui Ishii; Yohei Koseki; Nobutaka Takeda; Kei Tomiyoshi; Fusako Yamazaki; Yuki Yoshida; Riuko Ohashi; Yiwei Ling; Koji Ueda; Nobuko Moritoki; Kazuhiro Sato; Takahiro Nakajima; Yoshinori Hasegawa; Shujiro Okuda; Shinsuke Shibata; Shuji Terai
• Keywords: Spontaneous bacterial peritonitis; Pathogenesis

Abstract Background and Aims Decompensated cirrhosis with fibrosis progression causes portal hypertension followed by an oedematous intestinal tract. These conditions weaken the barrier function against bacteria in tract, a condition called leaky gut, resulting invasion bacterial components. Here, we investigated role of outer‐membrane vesicles (OMVs) Escherichia coli , which is representative pathogenic gut‐derived patients pathogenesis cirrhosis. Methods We involvement OMVs humans using human serum ascites samples also from E. mice mouse liver‐derived cells model. Results In vitro, induced inflammatory responses to macrophages neutrophils, including upregulation C‐type lectin domain family 4 member E (Clec4e), suppression albumin production hepatocytes but had relatively little direct effect on hepatic stellate cells. model, administration led increased liver inflammation, especially affecting activation macrophages, worsening decreasing production. Albumin weakened these changes. addition, multiple antibodies components were progressing Child‐Pugh grade, detected decompensated Conclusions conclusion, induce production, believe that our study paves way for future prevention treatment