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高胆红素血症新生儿肠道菌群特点及与β-葡萄糖醛酸苷酶活性的相关性
Characteristics of gut microbiota and its association with the activity of β-glucuronidase in neonates with hyperbilirubinemia
目的 探讨高胆红素血症新生儿肠道菌群特点及与β-葡萄糖醛酸苷酶（β-glucuronidase，β-GD）活性的关系。方法 选取2018年1~12月入院治疗的高胆红素血症新生儿50例为高胆红素血症组，选取非高胆红素血症新生儿30例为对照组。通过16S rRNA高通量测序方法分析两组新生儿肠道菌群的差异。通过酚酞-葡萄糖醛酸底物法测定高胆红素血症新生儿治疗前后肠道内的β-GD活性。结果 对治疗前高胆红素血症组和对照组肠道菌群分布属水平进行比较，发现两组间有52种细菌的丰度差异有统计学意义（P < 0.05）。对治疗后第3天高胆红素血症组和对照组入组3 d后肠道菌群分布属水平进行比较，发现两组间有42种细菌的丰度差异有统计学意义（P < 0.05）。高胆红素血症组新生儿治疗后，埃希氏菌属和葡萄球菌属在肠道内的含量明显低于治疗前（P < 0.05），粪便中β-GD活性较治疗前明显降低（P < 0.05）。高胆红素血症新生儿治疗前后粪便β-GD活性与葡萄球菌属和埃希氏菌属丰度均呈正相关（rs=0.5948~0.7245，均P < 0.01）。结论 高胆红素血症新生儿和非高胆红素血症新生儿肠道菌群存在差异。高胆红素血症新生儿粪便中β-GD活性与差异菌葡萄球菌属和埃希氏菌属丰度呈正相关。肠道菌群可能通过调节β-GD活性影响新生儿高胆红素血症的发生，通过对新生儿肠道菌群和β-GD活性进行测定和分析，可能对早期评估新生儿高胆红素血症的发生有一定的临床意义。
Objective To study the characteristics of gut microbiota and its association with the activity of β-glucuronidase (β-GD) in neonates with hyperbilirubinemia. Methods A total of 50 neonates with hyperbilirubinemia who were admitted in January to December, 2018, were enrolled as the hyperbilirubinemia group, and 30 neonates without hyperbilirubinemia were enrolled as the control group. The 16S rRNA high-throughput sequencing method was used to compare gut microbiota between the two groups. The phenolphthalein-glucuronic acid substrate method was used to measure the activity of β-GD in the intestinal tract of neonates with hyperbilirubinemia before and after treatment. Results The comparison of the distribution of gut microbiota at the genus level showed a significant difference in the abundance of 52 bacteria between the hyperbilirubinemia and control groups before treatment (P < 0.05), as well as a significant difference in the abundance of 42 bacteria between the hyperbilirubinemia group on day 3 after treatment and the control group on day 3 after enrollment (P < 0.05). After treatment, the hyperbilirubinemia group had significant reductions in the content of Escherichia and Staphylococcus in the intestinal tract (P < 0.05) and the activity of β-GD in feces (P < 0.05). The activity of β-GD in feces was positively correlated with the abundance of Staphylococcus and Escherichia before and after treatment in the neonates with hyperbilirubinemia (rs=0.5948-0.7245, P < 0.01). Conclusions There are differences in gut microbiota between the neonates with hyperbilirubinemia and those without hyperbilirubinemia. The activity of β-GD in feces is positively correlated with the abundance of Staphylococcus and Escherichia in neonates with hyperbilirubinemia. Gut microbiota may affect the development of neonatal hyperbilirubinemia by regulating the activity of β-GD. The determination and analysis of gut microbiota and β-GD activity may have certain clinical significance for the early assessment of the development of neonatal hyperbilirubinemia.
高胆红素血症 / 肠道菌群 / 16S rRNA高通量测序 / β-葡萄糖醛酸苷酶 / 新生儿
Hyperbilirubinemia / Gut microbiota / 16S rRNA high-throughput sequencing / β-glucuronidase / Neonate
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镇江市社会发展项目（SH2019055）；江苏省妇幼保健项目（F201648）。
