Gut microbiota can impact liver disease development via the gut-liver axis. Liver inflammation is a shared pathological event in various liver diseases and gut microbiota might influence this pathological process. In this study, we studied the influence of gut microbiota on the inflammatory response of the liver to lipopolysaccharide (LPS). The inflammatory response to LPS (1–10 μg/ml) of livers of specific-pathogen-free (SPF) or germ-free (GF) mice was evaluated ex vivo, using precision-cut liver slices (PCLS). LPS induced a more pronounced inflammatory response in GF PCLS than in SPF PCLS. Baseline TNF-α gene expression was significantly higher in GF slices as compared to SPF slices. LPS treatment induced TNF-α, IL-1β, IL-6 and iNOS expression in both SPF and GF PCLS, but the increase was more intense in GF slices. The anti-inflammatory markers SOCS3 and IRAK-M gene expression was significantly higher in GF PCLS than SPF PCLS at 24h with 1 µg/ml LPS treatment, and IL-10 was not differently expressed in GF PCLS than SPF PCLS. In addition, TLR-4 mRNA, but not protein, at basal level was higher in GF slices than in SPF slices. Taken together, this study shows that, in mice, the host microbiota attenuates the pro-inflammatory impact of LPS in the liver, indicating a positive role of the gut microbiota on the immune homeostasis of the liver.

肠道菌群可以通过肠肝轴影响肝脏疾病的发展。肝炎是各种肝脏疾病中共同的病理事件，肠道菌群可能会影响这一病理过程。在这项研究中，我们研究了肠道菌群对肝脏对脂多糖（LPS）的炎症反应的影响。离体评估了无特定病原（SPF）或无菌（GF）小鼠的肝脏对LPS（1-10μg/ ml）的炎症反应，使用精确切割的肝切片（PCLS）。与SPF PCLS相比，LPS在GF PCLS中引起更明显的炎症反应。与SPF切片相比，GF切片中的基线TNF-α基因表达明显更高。LPS处理可在SPF和GF PCLS中诱导TNF-α，IL-1β，IL-6和iNOS表达，但在GF切片中增加更为明显。用1 µg / ml LPS处理，在24 h时，GF PCLS中的抗炎标记SOCS3和IRAK-M基因表达显着高于SPF PCLS，并且与SPF PCLS相比，GF PCLS中IL-10的表达没有差异。此外，GF切片中的基础水平的TLR-4 mRNA而非蛋白水平高于SPF切片。两者合计，这项研究表明，在小鼠中，宿主菌群减弱了LPS对肝脏的促炎作用，表明肠道菌群对肝脏的免疫稳态具有积极作用。