肠道菌群丰度与病理性黄疸新生儿临床指标的相关性及诊断价值分析

Analysis of the correlation and diagnostic value of gut microbiota abundance with clinical indicators in neonates with pathological jaundice

摘要:

目的 探讨病理性黄疸新生儿与健康新生儿肠道菌群丰度的差异及其与临床指标的相关性，评估肠道菌群丰度在病理性黄疸新生儿诊断中的价值。方法 选取2022年9月—2023年6月宁波大学附属第一医院新生儿科收治的60例病理性黄疸新生儿为黄疸组，选取同期在该院体检的健康新生儿80例作为对照组。收集两组新生儿一般资料并采集静脉血进行临床检测。采集两组新生儿粪便并使用高通量16S rRNA基因测序技术检测两组新生儿粪便样本中菌群RNA，分析肠道菌群α多样性［Chao指数、Shannon指数、Simpson指数］，采用Pearson法分析临床指标与健康、病理性黄疸新生儿肠道菌群失调的相关性。采用受试者工作特征（ROC）曲线分析新生儿肠道菌群丰度与临床指标对病理性黄疸的诊断价值。结果 黄疸组高敏C反应蛋白（hs-CRP）、一氧化碳血红蛋白（CoHb）、白细胞计数（WBC）、血红蛋白浓度（HGB）、红细胞压积（HCT）、丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、γ-谷氨酰转肽酶（γGT）、总胆红素（TBIL）、直接胆红素（DBIL）水平均高于对照组（P <0.05）。两组新生儿红细胞计数（RBC）、中性粒细胞计数（NE）、血红蛋白（Hb）、血小板计数（PLT）、血小板压积（PCT）比较，差异均无统计学意义（P >0.05）。两组新生儿肠道菌群Shannon指数、Simpson指数、Chao指数比较，差异均无统计学意义（P >0.05）。黄疸组普拉梭菌属、柠檬酸杆菌属丰度高于对照组（P <0.05）。两组新生儿肠道埃希菌属、葡萄球菌属、克雷伯菌属、双歧杆菌属丰度比较，差异均无统计学意义（P >0.05）。Pearson相关性分析显示，病理性黄疸组新生儿hs-CRP、CoHb、WBC、ALT、γGT、TBIL、DBIL水平与肠道菌群普拉梭菌属呈正相关（r =0.280、0.330、0.375、0.160、0.229、0.470和0.449，均P <0.05），HGB、HCT、AST与肠道菌群普拉梭菌属无相关性（r =0.161、0.091和0.074，均P >0.05）。hs-CRP、CoHb、WBC、HGB、ALT、γGT、TBIL、DBIL水平与肠道菌群柠檬酸杆菌属呈正相关（r =0.360、0.394、0.475、0.246、0.223、0.256、0.581和0.542，均P <0.05），HCT、AST与肠道菌群柠檬酸杆菌属无相关性（r =0.148和0.118，均P >0.05）。ROC曲线分析结果显示，联合诊断效能最高，其曲线下面积为0.959（95% CI：0.926，0.992），敏感性为95.0%（95% CI：0.861，0.990），特异性为95.1%（95% CI：0.877，0.986）。结论 证实了病理性黄疸新生儿肠道菌群丰度与多样性的变化，其与血清胆红素水平有相关性。肠道菌群的丰度及多样性作为生物标志物，可能对病理性黄疸的早期诊断和治疗具有重要价值。

Abstract:

Objective To investigate the differences in gut microbiota abundance between neonates with pathological jaundice and healthy neonates, explore the correlation between gut microbiota and clinical indicators, and evaluate the diagnostic value of gut microbiota abundance in neonatal pathological jaundice.Methods Sixty neonates with pathological jaundice admitted to the Department of Neonatology at the Affiliated First Hospital of Ningbo University from September 2022 to June 2023 were included in the jaundice group, while eighty healthy neonates undergoing physical examination during the same period were selected as the control group. General data were collected from both groups, and venous blood was sampled for clinical testing. Fecal samples were collected, and high-throughput 16S rRNA gene sequencing was performed to analyze the RNA of gut microbiota. The α-diversity of gut microbiota was assessed using Chao, Shannon, and Simpson indices. The correlation between clinical indicators and gut microbiota dysbiosis in both healthy and jaundiced neonates was analyzed using Pearson correlation. The diagnostic value of gut microbiota abundance and clinical indicators for pathological jaundice was assessed using Receiver Operating Characteristic (ROC) curves.Results The jaundice group showed significantly higher levels of high-sensitivity C-reactive protein (hs-CRP), carboxyhemoglobin (CoHb), white blood cell count (WBC), hemoglobin concentration (HGB), hematocrit (HCT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γGT), total bilirubin (TBIL), and direct bilirubin (DBIL) compared to the control group (P < 0.05). There were no statistically significant differences in red blood cell count (rBC), neutrophil count (NE), hemoglobin (Hb), platelet count (PLT), or plateletcrit (PCT) between the two groups (P > 0.05). The Shannon, Simpson, and Chao indices of gut microbiota did not differ significantly between the two groups (P > 0.05). The abundance of Clostridium and Citrobacter was higher in the jaundice group compared to the control group (P < 0.05). There were no significant differences in the abundance of Escherichia, Staphylococcus, Klebsiella, and Bifidobacterium between the two groups (P > 0.05). Pearson correlation analysis indicated a positive correlation between hs-CRP, CoHb, WBC, ALT, γGT, TBIL, DBIL, and Clostridium abundance in the pathological jaundice group (r = 0.280, 0.330, 0.375, 0.160, 0.229, 0.470, and 0.449, all P < 0.05), with no correlation found for HGB, HCT, and AST (r = 0.161, 0.091, and 0.074, all P > 0.05). Similarly, hs-CRP, CoHb, WBC, HGB, ALT, γGT, TBIL, and DBIL were positively correlated with Citrobacter abundance (r = 0.360, 0.394, 0.475, 0.246, 0.223, 0.256, 0.581, and 0.542, all P < 0.05), with no correlation for HCT and AST (r = 0.148 and 0.118, both P > 0.05). The ROC curve analysis revealed that combined diagnostic efficacy was the highest, with an area under the curve (AUC) of 0.959 (95% CI: 0.926, 0.992), sensitivity of 95.0% (95% CI: 0.861, 0.990), and specificity of 95.1% (95% CI: 0.877, 0.986).Conclusion The study demonstrates changes in gut microbiota abundance and diversity in neonates with pathological jaundice and their correlation with serum bilirubin levels. The abundance and diversity of gut microbiota may serve as biomarkers, offering significant value for the early diagnosis and treatment of pathological jaundice.