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Purpose: Klebsiella pneumoniae-induced liver abscess and baiacterem is a serious infectious disease with high mortality. Secondary bile acids (SBAs) are produced by intestinal flora through the metabolism of primary bile acids and play a role in promoting or inhibiting inflammation in some diseases. However, the immunomodulatory role of SBAs in bacterial infections of the liver remains unclear. This study aimed to investigate the anti-inflammatory and liver-protective effects of SBAs in K. pneumoniae-infected mice. Methods: The absolute concentrations of deoxycholic acid (DCA) and lithocholic acid (LCA) in feces and serum were analyzed, and intestinal flora alterations between K. pneumoniae-infected and healthy control mice were examined. The effect of SBAs was investigated by analyzing the survival, tissue bacterial load, histopathology, and inflammatory factor levels in SBA-treated mice. The expression of crucial proteins implicated in the NF-κB pathway, as well as the G-protein-coupled bile acid receptor TGR5, was detected. Results: The content of SBAs in feces and serum of the K. pneumoniae-infected group was significantly reduced, and significant changes in the composition of the intestinal flora were detected. The intestinal flora are directly related to the synthesis of SBAs. Ruminococcaceae levels in K. pneumoniae-infected mice were significantly lower than in healthy control mice. Oral administration of SBAs improved the survival and liver pathology of K. pneumoniae-infected mice, and reduced the bacterial load and the level of inflammatory factors. SBAs down-regulated the expression of key proteins in the NF-κB inflammatory signaling pathway, including the phosphorylation of IκBα and NF-κB p50 and the nuclear translocation of NF-κB p65. The protective effect of SBAs may be dependent on high TGR5 expression. Conclusion: SBAs downregulate the NF-κB inflammatory signaling pathway through TGR5, protecting the liver and inhibiting inflammation in K. pneumoniae-induced liver abscess and bacteremia. [ABSTRACT FROM AUTHOR]

Introduction: Klebsiella pneumoniae is a pathogen commonly found in community-onset bacteremia. It causes an invasive syndrome that is frequently presented by metastatic infections and abscesses elsewhere and that is necessary for surgical or drainage intervention. To achieve a scoring algorithm to identify patients with community-onset K. pneumoniae bacteremia (CoKPB) who are at risk for abscess occurrences, a retrospective cohort study consisting of adults with CoKPB was conducted. Methods: A 6-year cohort study consisting of adults having community-onset monomicrobial K. pneumoniae bacteremia was conducted. In addition to clinical variables collected from medical records, the hypermucoviscosity (HMV)-related gene (rmpA and magA) and an HMV phenotype were integrated into the proposed scoring algorithm. Results: Of the 258 eligible adults, only 79 (30.6%) had abscesses related to bacteremia. Besides the presence of magA (ie, capsular serotype K1) and the HMV-phenotype, five clinical predictors were significantly associated with abscesses in a multivariate analysis: male gender, comorbidities with diabetes mellitus or neurological disorders, recent chemotherapy, and high c-reactive protein levels. Together, these predictors were used to calculate the CoKPB abscess score. Based on the scoring algorithm, a cut-off value of +2 yielded the high sensitivity (93.7%) and the acceptable specificity (50.8%); the area under the ROC curve was 0.83. Conclusion: A simple scoring algorithm that has substantial sensitivity and satisfactory specificity was proposed and the importance of the HMV phenotype or capsular K1 serotype was emphasized. The proposed predictive model needs external validation, but this scoring algorithm might be convenient and useful for clinicians. [ABSTRACT FROM AUTHOR]