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健康新生儿脐带血和胎粪中的胆汁酸代谢组:独特特征及意义

The bile acid metabolome in umbilical cord blood and meconium of healthy newborns: distinct characteristics and implications.

作者信息

Lu Chunxia, Gao Zhiyong, Zhang Siqi, Du Ke, Xu Die, Dong Wenbin, Zhang Yujiao, Lei Xiaoping

机构信息

Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.

Department of Obstetrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.

出版信息

PeerJ. 2024 Dec 13;12:e18506. doi: 10.7717/peerj.18506. eCollection 2024.

Abstract

OBJECTIVE

To characterize the bile acid metabolomic profiles of umbilical cord blood and meconium in healthy newborns.

METHODS

Fifteen healthy newborns, which born in the Obstetrics Department of the Affiliated Hospital of Southwest Medical University between July 1 and August 31, 2023, were selected as study subjects. Umbilical cord blood and meconium samples were collected, and bile acid metabolomics were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry.

RESULTS

The ratio of primary to secondary bile acids in cord blood was significantly higher than in meconium [2.64 (2.49, 5.70) . 0.99 (0.37, 1.58), Z = -3.80, < 0.05]. The ratio of unconjugated to conjugated bile acids was notably higher in cord blood than in meconium [0.14 (0.07, 0.18) . 0.01 (0.01, 0.04), Z = -3.88, < 0.05]. The ratio of cholic acid to chenodeoxycholic acid in conjugated primary bile acids was significantly lower in cord blood than in meconium [0.59 (0.19, 0.75) . 2.21 (1.34, 3.04), Z = -4.21, < 0.05], but the ratio of cholic acid to chenodeoxycholic acid in secondary bile acids was significantly higher in cord blood than in meconium [0.42 (0.21, 0.63) . 0.03 (0.01, 0.05), Z = -4.54, < 0.05]. Only three primary bile acids (taurochenodeoxycholic acid, glycochenodeoxycholic acid, and glycochenodeoxycholic acid 3-glucoside in umbilical cord blood) were correlated with their downstream metabolites in meconium (with hyodesoxycholic acid (r = -0.66, = 0.01), tauro-ω-muricholic acid (r = 0.52, = 0.048) and ursodeoxycholic acid-7S (r = -0.53, = 0.04), respectively). In meconium, most of primary bile acids were correlated with their downstream metabolites ( all < 0.05): cholic acid was positively correlated with 3-dehydrocholic acid, taurocholic acid was positively correlated with taurodeoxycholic acid and 3-dehydrocholic acid, glycocholic acid was positively correlated with 3-dehydrocholic acid, chenodeoxycholic acid was positively correlated with glycoursodeoxycholic acid, taurolithocholic acid, and 7-keto lithocholic acid and negatively correlated with isolithocholic acid. Taurochenodeoxycholic acid was positively correlated with taurohyodeoxycholic acid, tauroursodeoxycholic acid, glycoursodeoxycholic acid, taurolithocholic acid, tauro-ω-muricholic acid, and glycohyodeoxycholic acid, while glycochenodeoxycholic acid was positively correlated with tauroursodeoxycholic acid, glycoursodeoxycholic acid, taurolithocholic acid, and glycohyodeoxycholic acid, and negatively correlated with isolithocholic acid.

CONCLUSION

The bile acid metabolites in umbilical cord blood and meconium differ significantly, and the downstream bile acid metabolites in meconium are predominantly correlated with their upstream bile acids in meconium, but not those bile acids in umbilical cord blood. These findings contribute to a better understanding of bile acid metabolism and lay the foundation for future research in this topic.

摘要

目的

表征健康新生儿脐带血和胎粪中的胆汁酸代谢组学特征。

方法

选取2023年7月1日至8月31日在西南医科大学附属医院产科出生的15例健康新生儿作为研究对象。收集脐带血和胎粪样本,采用超高效液相色谱 - 串联质谱法分析胆汁酸代谢组学。

结果

脐带血中初级胆汁酸与次级胆汁酸的比值显著高于胎粪[2.64(2.49, 5.70) . 0.99(0.37, 1.58),Z = -3.80, < 0.05]。脐带血中未结合胆汁酸与结合胆汁酸的比值显著高于胎粪[0.14(0.07, 0.18) . 0.01(0.01, 0.04),Z = -3.88, < 0.05]。脐带血中结合型初级胆汁酸中胆酸与鹅去氧胆酸的比值显著低于胎粪[0.59(0.19, 0.75) . 2.21(1.34, 3.04),Z = -4.21, < 0.05],但脐带血中次级胆汁酸中胆酸与鹅去氧胆酸的比值显著高于胎粪[0.42(0.21, 0.63) . 0.03(0.01, 0.05),Z = -4.54, < 0.05]。脐带血中仅3种初级胆汁酸(脐带血中的牛磺鹅去氧胆酸、甘氨鹅去氧胆酸和甘氨鹅去氧胆酸3 - 葡萄糖苷)与其在胎粪中的下游代谢产物相关(分别与猪去氧胆酸(r = -0.66, = 0.01)、牛磺 - ω - 鼠胆酸(r = 0.52, = 0.048)和熊去氧胆酸 - 7S(r = -0.53, = 0.04)相关)。在胎粪中,大多数初级胆汁酸与其下游代谢产物相关(所有 < 0.05):胆酸与3 - 脱氢胆酸呈正相关,牛磺胆酸与牛磺去氧胆酸和3 - 脱氢胆酸呈正相关,甘氨胆酸与3 - 脱氢胆酸呈正相关,鹅去氧胆酸与甘氨熊去氧胆酸、牛磺石胆酸和7 - 酮石胆酸呈正相关,与异石胆酸呈负相关。牛磺鹅去氧胆酸与牛磺猪去氧胆酸、牛磺熊去氧胆酸、甘氨熊去氧胆酸、牛磺石胆酸、牛磺 - ω - 鼠胆酸和甘氨猪去氧胆酸呈正相关,而甘氨鹅去氧胆酸与牛磺熊去氧胆酸、甘氨熊去氧胆酸、牛磺石胆酸和甘氨猪去氧胆酸呈正相关,与异石胆酸呈负相关。

结论

脐带血和胎粪中的胆汁酸代谢产物存在显著差异,胎粪中胆汁酸的下游代谢产物主要与其胎粪中的上游胆汁酸相关,而非脐带血中的胆汁酸。这些发现有助于更好地理解胆汁酸代谢,并为该主题的未来研究奠定基础。

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