The intensive crosstalk between the liver and the intestine performs many essential functions. This crosstalk is important for natural immune surveillance, adaptive immune response regulation and nutrient metabolism and elimination of toxic bacterial metabolites. The interaction between the gut microbiome and bile acids is bidirectional. The gut microbiome regulates the synthesis of bile acids and their biological signaling activity and circulation via enzymes. Similarly, bile acids also shape the composition of the gut microbiome by modulating the host’s natural antibacterial defense and the intestinal immune system. The interaction between bile acids and the gut microbiome has been implicated in the pathophysiology of many intestinal and extra intestinal diseases, especially liver diseases. As essential mediators of the gut-liver crosstalk, bile acids regulate specific host metabolic pathways and modulate the inflammatory responses through farnesoid X-activated receptor and G protein-coupled bile acid receptor 1. Several clinical trials have demonstrated the signaling effects of bile acids in the context of liver diseases. We hypothesize the existence of a gut microbiome-bile acids-liver triangle and explore the potential therapeutic strategies for liver diseases targeting the triangle.

Background: Lithocholic acid are essential signaling molecules that mediate the relationship between the gut microbiome and liver function by regulating inflammation. The purpose of this study is to investigate the role of lithocholic acid in liver fibrosis. Methods: A liver fibrosis mouse model was induced by carbon tetrachloride followed by gavage of lithocholic acid, and the effects of lithocholic acid were evaluated by serum biochemical analysis and liver histology. Plasma cytokine levels and the number of immune cells were determined by cytometric bead array and flow cytometry, respectively. Results: Lithocholic acid treatment increased the recruitment of NK cells and reduced the activation of NKT cells, and reduced M1 macrophages differentiation and increased M2 macrophages differentiation. Furthermore, the lithocholic acid prevented inflammatory liver disease by reducing TNF-α and IL-22 secretion. However, the effect of lithocholic acid disappeared when the host gut microbiome was treated with antibiotics. Conclusions: It showed that the activation of lithocholic acid-mediated signaling was linked to the inhibition of inflammation and improvement of liver fibrosis. The role of lithocholic acid in liver fibrosis is mediated by the gut microbiome. The association between the gut microbiome, lithocholic acid, and liver function can serve as a therapeutic target for liver fibrosis.

Background and Objective Polymicrobial bloodstream infections (PBSI) in hospitalized patients are associated with increased mortality, while few studies have characterized the clinical features in this population. This study aimed to assess the risk factors and short-term prognosis of PBSI in hospitalized patients.Materials and Methods 4066 patients with culture-positive blood were included between January 1, 2015 and December 31, 2017 in the First Affiliated Hospital of Zhejiang University School of Medicine (Hangzhou, China) in our study. 218 patients were diagnosed as PBSI. The patients were divided into two groups according to the outcome after 30-day follow-up. The number of survival group were 129, while the number of non-survival group were 89. The clinical data, identified microorganisms and severity models were compared between the two groups. A cox regression model was used to identify the risk factors of 30-day mortality in PBSI patients. Five prediction models were compared by Z-test to test the value of these models to predict outcome of PBSI.Results The patients in the non-survival group were more likely to receive inappropriate antibiotic therapy at the time of PBSI and showed more severe in systemic inflammatory. They were more likely to develop to be septic shock and to be admitted in ICU than the patients in the survival group. Inappropriate initial empirical antimicrobial therapy (HR=1.713 95% CI: 1.063-2.760, p=0.027), white blood cell (HR=1.740 95% CI: 1.002-3.020, p=0.049) and platelet (HR=2.940 95% CI: 1.754-4.930, p<0.001) were independent risk factors for 30-day mortality in PBSI patients. SOFA (AUROC=0.882, 95% CI=0.832-0.922) scores was a good prognostic scoring system for predicting short-term mortality in PBSI patients. The SOFA score was more valuable than the other four models in predicting the outcome of PBSI according to the Z-test (p<0.05).Discussion and Conclusions Inappropriate initial empirical antimicrobial therapy, white blood cell and platelet were closely associated with short-term mortality.