PDF(Pubmed)
Abstract：
This study mainly investigated the effects of berberine (BBR) on the bile acid metabolism in gut-liver axis and the microbial community in large intestine of weaned piglets challenged with enterotoxigenic Escherichia coli (ETEC) by microbiome and metabolome analyses. Sixty-four piglets were randomly assigned to four groups including Control group, BBR group, ETEC group, and BBR + ETEC group. Dietary BBR supplementation upregulated the colonic mRNA expression of Occludin, Claudin-5, trefoil factor 3 (TFF3), and interleukin (IL)-10, and downregulated colonic IL-1β and IL-8 mRNA expression in piglets challenged with ETEC K88 (p < 0.05). The hepatic non-targeted metabolome results showed that dietary BBR supplementation enriched the metabolic pathways of primary bile acid biosynthesis, tricarboxylic acid cycle, and taurine metabolism. The hepatic targeted metabolome analyses showed that BBR treatment increased the hepatic concentrations of taurocholic acid (TCA) and taurochenodeoxycholic acid (TDCA), but decreased the hepatic cholic acid (CA) concentration (p < 0.05). Further intestinal targeted metabolome analyses indicated that the deoxycholic acid (DCA), hyocholic acid (HCA), 7-ketodeoxycholic acid (7-KDCA), and the unconjugated bile acid concentrations in ileal mucosa was decreased by dietary BBR treatment (p < 0.05). Additionally, BBR treatment significantly upregulated the hepatic holesterol 7 α-hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1) mRNA expression, and upregulated the ileal mRNA expression of farnesoid X receptor (FXR) and apical sodium-dependent bile acid transporter (ASBT) as well as the colonic mRNA expression of FXR, fibroblast growth factor19 (FGF19), takeda G protein-coupled receptor 5 (TGR5) and organic solute transporters beta (OST-β) in piglets (p < 0.05). Moreover, the microbiome analysis showed that BBR significantly altered the composition and diversity of colonic and cecal microbiota community, with the abundances of Firmicutes (phylum), and Lactobacillus and Megasphaera (genus) significantly increased in the large intestine of piglets (p < 0.05). Spearman correlation analysis showed that the relative abundances of Megasphaera (genus) were positively correlated with Claudin-5, Occludin, TFF3, and hepatic TCDCA concentration, but negatively correlated with hepatic CA and glycocholic acid (GCA) concentration (p < 0.05). Moreover, the relative abundances of Firmicute (phylum) and Lactobacillus (genus) were positively correlated with hepatic TCDCA concentration (p < 0.05). Collectively, dietary BBR supplementation could regulate the gut microbiota and bile acid metabolism through modulation of gut-liver axis, and attenuate the decreased intestinal tight junction expression caused by ETEC, which might help maintain intestinal homeostasis in weaned piglets.
摘要：
本研究主要通过微生物组和代谢组分析研究小檗碱(BBR)对产肠毒素大肠杆菌(ETEC)断奶仔猪肠-肝轴胆汁酸代谢和大肠微生物群落的影响。将64头仔猪随机分为4组,包括对照组,BBR组,ETEC组,和BBR+ETEC组。膳食补充BBR上调Occludin的结肠mRNA表达，Claudin-5，三叶因子3（TFF3），和白细胞介素（IL）-10，并下调了用ETECK88攻击的仔猪的结肠IL-1β和IL-8mRNA表达（p<0.05）。肝脏非靶向代谢组结果表明，膳食补充BBR丰富了初级胆汁酸生物合成的代谢途径，三羧酸循环，和牛磺酸代谢.肝靶向代谢组分析表明，BBR治疗增加了牛磺胆酸（TCA）和牛磺鹅去氧胆酸（TDCA）的肝浓度，但降低了肝胆酸（CA）浓度（p<0.05）。进一步的肠道靶向代谢组分析表明，脱氧胆酸(DCA)，猪胆酸（HCA），7-酮脱氧胆酸（7-KDCA），通过饮食BBR治疗，回肠粘膜中未结合的胆汁酸浓度降低（p<0.05）。此外,BBR处理显著上调肝硬脂醇7α-羟化酶(CYP7A1)和甾醇27-羟化酶(CYP27A1)mRNA表达,并上调了法尼醇X受体（FXR）和根尖钠依赖性胆汁酸转运体（ASBT）的回肠mRNA表达以及FXR的结肠mRNA表达，成纤维细胞生长因子19（FGF19），武田G蛋白偶联受体5(TGR5)和有机溶质转运蛋白β(OST-β)在仔猪中的表达(p<0.05)。此外，微生物组分析表明，BBR显著改变了结肠和盲肠微生物群落的组成和多样性，随着Firmicutes（门）的丰富，乳杆菌和Megasphaera(属)在仔猪大肠中显著增加(p<0.05)。Spearman相关分析表明，Megasphaera（属）的相对丰度与Claudin-5，Occludin，TFF3和肝TCDCA浓度，但与肝CA和甘胆酸（GCA）浓度呈负相关（p<0.05）。此外，Firmicute（门）和乳酸杆菌（属）的相对丰度与肝TCDCA浓度呈正相关（p<0.05）。总的来说，膳食补充BBR可以通过调节肠-肝轴调节肠道菌群和胆汁酸代谢,并减弱由ETEC引起的肠紧密连接表达降低，这可能有助于维持断奶仔猪的肠道稳态。
