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

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 the intestinal tract, a condition called leaky gut, resulting in invasion by bacteria and bacterial components. Here, we investigated the role of outer-membrane vesicles (OMVs) of Escherichia coli, which is the representative pathogenic gut-derived bacteria in patients with cirrhosis in the pathogenesis of cirrhosis. Methods:We investigated the involvement of OMVs in humans using human serum and ascites samples and also investigated the involvement of OMVs from E. coli in mice using mouse liver-derived cells and a mouse cirrhosis model.

Urinary NGAL in gastrointestinal diseases can be used as an indicator of early infection in addition to acute kidney injury marker

“… 14 , 15 In patients with liver cirrhosis, the invasion of enteric bacteria and bacteria‐associated substances, such as lipopolysaccharide (LPS) and pathogen‐associated molecular patterns (PAMPs) (bacterial invasion is called bacterial translocation), can cause extremely serious liver and systemic conditions. 16 These not only cause liver damage, but also lead to systemic inflammation. These conditions lead to cirrhosis‐associated immune dysfunction (CAID).…”

Analysis of distribution, collection, and confirmation of capacity dependency of small extracellular vesicles toward a therapy for liver cirrhosis

“…Parenchymal and non-parenchymal cell fractions were isolated using liver perfusion medium (Thermo Fisher Scientific) and liver digestive medium (Thermo Fisher Scientific). Hepatocytes were obtained from the parenchymal cell fraction, and HSCs and LSECs were obtained from the non-parenchymal cell fraction [ 3 ].…”

“…As portal hypertension and hepatic dysfunction progress, various symptoms such as bleeding, jaundice, edema, ascites, hepatic encephalopathy, and increased infections occur owing to changes in circulatory dynamics, invasion of intestinal bacteria and components, systemic inflammation, immune system changes, and metabolic and nutritional disorders, which significantly reduce the quality of life and lead to fatal complications in patients. Liver transplantation is the ultimate treatment; however, donor shortage poses a serious challenge [ 2 , 3 ].…”

Gut microbe and hepatic macrophage polarization in non-alcoholic fatty liver disease

“…These activated M1 macrophages, through the mTOR-S6K1-SREBP-1 signaling pathway, amplify disturbances in hepatic lipid metabolism in NAFLD mice, exacerbating liver injury and promoting NAFLD progression ( Zhang et al, 2020 ). In the context of cirrhosis, an advanced stage of NAFLD, outer-membrane vesicles from E. coli have been shown to induce C-type lectin domain family 4 member E (Clec4e) expression in hepatic macrophages and neutrophils, which influences hepatic immunity, activates hepatic M1 macrophages, and exacerbates cirrhosis development ( Natsui et al, 2023 ).…”