Data_Sheet_1_Alterations in bile acids as metabolic signatures in the patients with human adenovirus type 7 infection.pdf

ObjectivesThe changes in metabolism by human adenovirus (HAdV) infection was unclear. The potential mechanism of HAdV-7 causing acute respiratory tract infection was explored.MethodsTotally 35 patients with HAdV-7 infection, 32 asymptomatic cases with HAdV-7 and 14 healthy controls were enrolled from an outbreak of HAdV-7 in the army. The serum samples were analyzed by untargeted and targeted metabolomics. The effects of differential metabolites were verified on HAdV-7 replication in an A549 cell line.ResultsThe untargeted metabolomics analysis revealed more significant changes in the classes of sphingolipids, polyketides, glycerolipids, fatty acyls, and carboxylic acids and their derivatives in the patients with HAdV-7 than in healthy controls. Two key metabolic pathways of secondary and primary bile acid biosynthesis were noted from pathway enrichment analysis. Targeted metabolomics analysis showed that the levels of unconjugated bile acids in the patients were significantly lower, while the levels of glyco- and tauro- conjugated bile acids in patients and asymptomatic cases were higher than those in the healthy controls. The profiles of cytokines and peripheral lymphocyte subsets obviously varied at different levels of bile acids, with significant differences after HAdV-7 infection. A cell verification test demonstrated that the replication of HAdV-7 significantly reduced when GCDCA and TCA were added.ConclusionBile acids inhibited HAdV-7 replication in vitro. Alterations in bile acids was metabolic signatures of HAdV-7 infected subjects, and our results suggested bile acids might play protective roles against HAdV-7 infection.

研究目标：人类腺病毒（HAdV）感染引起的代谢变化尚不明确。探讨了HAdV-7引发急性呼吸道感染的潜在机制。
研究方法：从军队中HAdV-7疫情中招募了35例HAdV-7感染患者、32例无症状HAdV-7携带者和14名健康对照者。通过非靶向和靶向代谢组学分析了血清样本。在A549细胞系中，验证了差异代谢物对HAdV-7复制的影响。
研究结果：非靶向代谢组学分析显示，与健康对照者相比，HAdV-7感染患者的鞘脂类、聚酮类、甘油酯、脂肪酸酰基和羧酸及其衍生物的类别发生了更显著的变化。通路富集分析中，发现了次级和初级胆汁酸生物合成的两个关键代谢途径。靶向代谢组学分析表明，患者的非结合胆汁酸水平显著降低，而患者和无症状携带者的糖基化和牛磺酸结合胆汁酸水平高于健康对照者。在胆汁酸的不同水平上，细胞因子和外周淋巴细胞亚群的水平明显不同，HAdV-7感染后差异显著。细胞验证实验表明，添加GCDCA和TCA后，HAdV-7的复制显著减少。
研究结论：胆汁酸抑制了体外HAdV-7的复制。胆汁酸的变化是HAdV-7感染个体的代谢特征，我们的结果表明胆汁酸可能在抵御HAdV-7感染中发挥保护作用。