ObjectiveThe significance of the liver-microbiome axis has been increasingly recognised as a major modulator of autoimmunity. The aim of this study was to take advantage of a large well-defined corticosteroids treatment-naïve group of patients with autoimmune hepatitis (AIH) to rigorously characterise gut dysbiosis compared with healthy controls.DesignWe performed a cross-sectional study of individuals with AIH (n=91) and matched healthy controls (n=98) by 16S rRNA gene sequencing. An independent cohort of 28 patients and 34 controls was analysed to validate the results. All the patients were collected before corticosteroids therapy.ResultsThe gut microbiome of steroid treatment-naïve AIH was characterised with lower alpha-diversity (Shannon and observed operational taxonomic units, both p<0.01) and distinct overall microbial composition compared with healthy controls (p=0.002). Depletion of obligate anaerobes and expansion of potential pathobionts including Veillonella were associated with disease status. Of note, Veillonella dispar, the most strongly disease-associated taxa (p=8.85E–8), positively correlated with serum level of aspartate aminotransferase and liver inflammation. Furthermore, the combination of four patients with AIH-associated genera distinguished AIH from controls with an area under curves of approximately 0.8 in both exploration and validation cohorts. In addition, multiple predicted functional modules were altered in the AIH gut microbiome, including lipopolysaccharide biosynthesis as well as metabolism of amino acids that can be processed by bacteria to produce immunomodulatory metabolites.ConclusionOur study establishes compositional and functional alterations of gut microbiome in AIH and suggests the potential for using gut microbiota as non-invasive biomarkers to assess disease activity.

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Our results suggest that cucurbitacin B may have a therapeutic value in suppressing the growth of human hepatocellular carcinoma. The mechanism may be attributable to the suppression of STAT3 phosphorylation.

Cucurbitacins are compounds isolated from various plant families, which have been used as folk medicines for centuries in countries such as India and China because of their wide spectrum of pharmacological activities such as cytotoxic, anti-inflammatory, and anticancer effects. Accumulated evidences have shown that cucurbitacin B inhibits the growth of numerous human cancer cell lines and tumor xenografts. To determine whether cucurbitacin B can inhibit the growth of laryngeal squamous cell carcinoma, in the present study we investigated the antitumor effect of cucurbitacin B on Hep-2 cells. Hep-2 cells were treated with different concentrations of cucurbitacin B for different time. Cell proliferation, cell cycle distribution, and cell apoptosis were evaluated using MTT assay, flow cytometry, and fluorescent microscopy. It was found that cucurbitacin B exhibited significant efficacy in growth inhibition, cell cycle arrest at G2/M phase, and apoptosis induction in a dose- and time-dependent manner. Measuring the modulation of regulators in the cell cycle, apoptosis and signal transductions by Western blot analysis showed that the effect of cucurbitacin B was due to suppression of the expression of p-STAT3, Bcl-2, and cyclin B1. Moreover, in vivo studies were performed in a mouse xenograft model, where cucurbitacin B inhibited tumor growth in a dose-dependent manner. In conclusion, the antitumor effect of cucurbitacin B on Hep-2 cells was due to the induction of cell cycle arrest as well as apoptosis. The possible mechanisms underlying the action might be attributed to the suppression of STAT3 phosphorylation. This investigation suggests a potential clinical application of cucurbitacin B for the treatment of laryngeal cancer patients.

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