通过门静脉的肠道代谢物影响多种肝功能，包括再生。在这里，我们研究了肝再生过程中门静脉和外周血清中肠道微生物群衍生的代谢物。我们开发了 70% 部分肝切除术 (PHx) 的大鼠模型，有或没有通过为期三周的抗生素 (Abx) 治疗进行肠道微生物群调节。不使用 Abx 的假手术作为对照，并与使用 Abx 的假手术进行比较。通过肝组织中增殖细胞核抗原（PCNA）蛋白和原代肝细胞中细胞周期蛋白基因的表达来评估 PHx 后第 2 天的肝再生。采用基于门脉和外周静脉血清代谢组学的高压液相色谱-质谱法 (HPLC-MS) 来鉴定差异改变的代谢物 (DAM)。与对照组相比，PHx后第2天的大鼠肝脏显示PCNA阳性细胞的平均数量显着上调，这与肝细胞中细胞周期基因的表达呈正相关。在 Abx 处理的 PHx 中，我们观察到与 PHx 相比，肝细胞中 PCNA 阳性率降低，各种细胞周期蛋白基因表达下调。我们在门静脉血清中鉴定出对照与 PHx 之间有 224 个 DAM，而经 Abx 处理的 PHx 与 PHx 之间有 189 个 DAM。许多常见的 DAM 在门静脉血清中的 PHx 与对照以及 Abx PHx 与 PHx 中表现出相反的表达趋势，例如 1-磷酸鞘氨醇和脱氧胆酸。脱氧胆酸的体外研究表明，它可以增强原代肝细胞和肝细胞类器官的活力和增殖。该研究强调了门血中脱氧胆酸在增强肝细胞增殖以及随后的肝脏再生方面的关键作用。

Gut metabolites via the portal vein affect several liver functions, including regeneration. Here, we investigated gut microbiota-derived metabolites in portal and peripheral serum during liver regeneration. We developed rat models of 70% partial hepatectomy (PHx) with and without prior gut microbiota modulation by three-week antibiotic (Abx) treatment. Sham without Abx were used as controls and compared to sham with Abx. Liver regeneration at day 2 following PHx was assessed by expression of proliferating cell nuclear antigen (PCNA) protein in liver tissues and cyclin genes in primary hepatocytes. High pressure liquid chromatography-mass spectrometry (HPLC-MS) based portal and peripheral venous serum metabolomics was performed to identify differentially altered metabolites (DAMs). Compared to controls, rat livers at day 2 post-PHx showed significant upregulation in the average number of PCNA-positive cells, which positively correlated with the expression of cell cycle genes in hepatocytes. In Abx-treated PHx, we observed reduced PCNA-positivity and downregulation in gene expression of various cyclins in hepatocytes compared to PHx. We identified 224 DAMs between controls vs PHx and 189 DAMs between Abx-treated PHx vs PHx in portal serum. Many common DAMs showed opposite expression trends in PHx vs controls and then Abx+PHx vs PHx in portal serum, such as sphingosine-1-phosphate and deoxycholic acid. In vitro studies with deoxycholic acid demonstrated that it enhanced the viability and proliferation of primary hepatocytes and hepatocyte organoids. The study underscores the critical role of deoxycholic acid in portal blood in enhancing hepatocyte proliferation and subsequently, liver regeneration.