新生儿胆汁淤积性黄疸血清胆红素水平与肠道菌群失调的相关性

doi:10.3969/j.issn.1004-583X.2022.12.010

摘要/Abstract

摘要：

目的探讨新生儿胆汁淤积性黄疸血清胆红素水平与肠道菌群失调的相关性。方法选取2019年8月至2021年8月南阳市中心医院的新生儿胆汁淤积性黄疸患儿109例,同时选取母乳性黄疸患儿68例,健康新生儿80例。检测3组血清中胆红素水平和粪便标准肠道菌群,对比3组门水平优势菌群和属水平优势菌群的差异,采用Pearson相关系数分析血清胆红素水平与肠道菌群及肠道菌群失调的相关性。结果胆汁淤积症组丙氨酸氨基转移酶(ALT)、直接胆红素水平和总胆红素比值(DBIL/TBIL)明显高于健康组和母乳性黄疸组(P均<0.05),胆汁淤积症组Ⅱ度菌群失调和Ⅲ度菌群失调占比明显高于健康组和母乳性黄疸组(P<0.05);胆汁淤积症组拟杆菌门和厚壁菌门水平显著高于母乳性黄疸组和健康组(P<0.05),胆汁淤积症组变形菌门水平显著低于母乳性黄疸组(P<0.05),胆汁淤积症组中放线菌门水平明显低于健康组和母乳性黄疸组(P均<0.05);胆汁淤积症组双歧杆菌和乳酸杆菌丰度显著低于健康组和母乳性黄疸组(P<0.05),胆汁淤积症组大肠杆菌和肠球菌丰度明显高于健康组和母乳性黄疸组(P<0.05),胆汁淤积症组双歧杆菌/大肠杆菌(B/E)值低于健康组和母乳性黄疸组(P<0.05);Pearson相关分析发现,ALT、TBIL、DBIL、DBIL/TBIL与拟杆菌门、厚壁菌门呈正相关(均P<0.05),与放线菌门呈负相关(均P<0.05);TBIL与双歧杆菌、B/E值呈负相关(均P<0.05),与大肠杆菌、肠球菌呈正相关(均P<0.05);DBIL与双歧杆菌、B/E值呈负相关(均P<0.05);DBIL/TBIL与双歧杆菌、大肠杆菌、肠球菌、B/E值呈负相关(均P<0.05)。结论胆汁淤积性黄疸患儿菌群失调,双歧杆菌明显减少,且血清胆红素水平与菌群具有一定的相关性,积极补充益生菌可能成为治疗胆汁淤积性黄疸一种有效方式。

关键词: 黄疸, 新生儿, 胆红素, 肠道菌群失调, 双歧杆菌

Abstract:

Objective To investigate the correlation between serum bilirubin level and the imbalance of normal gut microbiota in neonates with cholestatic jaundice. Methods A total of 109 neonates with cholestatic jaundice treated in Nanyang Central Hospital from August 2019 to August 2021were selected as the cholestatic jaundice group, 68 neonates with breast milk jaundice were selected as the breast milk jaundice group, and 80 healthy neonates during the same period were selected as the healthy group. Serum bilirubin level andgut microbiotain stools were detected. Differences in the dominant flora at the level of phylum and genus in three groups were compared. The correlation between serum bilirubin level and the imbalance of normal gut microbiota was analyzed by Pearson’s correlation coefficient. Results Serum level of alanine aminotransferase (ALT) and direct bilirubin and total bilirubin ratio (DBIL/TBIL) in cholestatic jaundice group were significantly higher than those in healthy group and breast milk jaundice group (all P<0.05). The proportion of grade Ⅱ and Ⅲ imbalance of gut microbiota was significantly higher in cholestatic jaundice group than that in the healthy group and breast milk jaundice group (P<0.05).The abundances of Bacteroides and Firmicutes in cholestatic jaundice group were significantly higher than those in breast milk jaundice group and healthy group (P<0.05).The abundances of Bifidobacteria and Lactobacillus in cholestatic jaundice group were significantly lower than that in healthy group and breast milk jaundice group (P<0.05), and the abundances of Escherichia coli and Enterococcus in cholestatic jaundice group weresignificantly higher than that in healthy group and breast milk jaundice group (P<0.05). The ratio of Bifidobacteria/Escherichia coli (B/E) in cholestatic jaundice group was significantly lower than that in healthy group and breast milk jaundice group (P<0.05).ALT, TBIL, DBIL, DBIL/TBIL were positively correlated with the abundances of Bacteroides and Firmicutes (all P<0.05), and negatively correlated with that of Actinomyces (all P<0.05).TBIL was negatively correlated with the abundance of Bifidobacterium and B/E (P<0.05), and positively correlated with abundances of Escherichia coli and Enterococcus (P<0.05).DBIL was negatively correlated with the abundance of Bifidobacterium and B/E (P<0.05) DBIL/TBIL were negatively correlated with the abundances of Bifidobacterium, Escherichia coli, and Enterococcus, and B/E (all P<0.05). Conclusion The gut microbiota of neonates with cholestatic jaundice is imbalance, with significantly reduced abundance of Bifidobacteria, and the serum bilirubin level has a certain correlation with the gut microbiota. An active supplement of probiotics may be an effective way to treat cholestatic jaundice.

Key words: jaundice, neonatal, bilirubin, gut microbiota imbalance, Bifidobacterium

中图分类号:

R722.17

齐玉敏, 王友军. 新生儿胆汁淤积性黄疸血清胆红素水平与肠道菌群失调的相关性[J]. 临床荟萃, 2022, 37(12): 1117-1121.

Qi Yumin, Wang Youjun. Correlation between serum bilirubin level and the imbalance of the normal gut microbiota in neonates with cholestatic jaundice[J]. Clinical Focus, 2022, 37(12): 1117-1121.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2022.12.010

https://huicui.hebmu.edu.cn/CN/Y2022/V37/I12/1117

图/表 5

表1 3组临床特征比较

临床指标	健康组 (n=80)	母乳性黄疸组 (n=68)	胆汁淤积性黄疸组 (n=109)	χ²/ $F$ 值	P值
性别(男/女,例)	47/33	42/26	63/46	2.115	0.764
年龄(d)	14.97±5.21	15.36±5.05	15.23±5.19	1.037	0.942
母乳喂养[例(%)]	68(85.00)	55(80.88)	93(85.32)	0.949	1.253
阴道分娩[例(%)]	53(66.25)	46(67.65)	74(67.89)	1.313	0.815
ALT(IU/L)	23.16±3.79	25.13±16.54	129.37±118.69^*	44.657	<0.01
TBIL(μmol/L)	8.21±0.04	211.18±65.76^*	169.24±77.56^*#	27.848	<0.01
DBIL(μmol/L)	10.14±4.58	11.97±5.79	81.03±38.63^*	38.434	<0.01
DBIL/TBIL(%)	4.97±1.96	5.98±3.57	49.89±10.93^*	19.545	<0.01
菌群正常和Ⅰ度菌群失调[例(%)]	77(96.25)	61(89.71)	59(54.13)	10.838	0.004
Ⅱ度菌群失调[例(%)]	2(2.50)	5(7.35)	39(35.78)	19.273	<0.01
Ⅲ度菌群失调[例(%)]	1(1.25)	2(2.94)	11(10.09)	9.252	0.009

表1 3组临床特征比较

临床指标	健康组 (n=80)	母乳性黄疸组 (n=68)	胆汁淤积性黄疸组 (n=109)	χ²/ $F$ 值	P值
性别(男/女,例)	47/33	42/26	63/46	2.115	0.764
年龄(d)	14.97±5.21	15.36±5.05	15.23±5.19	1.037	0.942
母乳喂养[例(%)]	68(85.00)	55(80.88)	93(85.32)	0.949	1.253
阴道分娩[例(%)]	53(66.25)	46(67.65)	74(67.89)	1.313	0.815
ALT(IU/L)	23.16±3.79	25.13±16.54	129.37±118.69^*	44.657	<0.01
TBIL(μmol/L)	8.21±0.04	211.18±65.76^*	169.24±77.56^*#	27.848	<0.01
DBIL(μmol/L)	10.14±4.58	11.97±5.79	81.03±38.63^*	38.434	<0.01
DBIL/TBIL(%)	4.97±1.96	5.98±3.57	49.89±10.93^*	19.545	<0.01
菌群正常和Ⅰ度菌群失调[例(%)]	77(96.25)	61(89.71)	59(54.13)	10.838	0.004
Ⅱ度菌群失调[例(%)]	2(2.50)	5(7.35)	39(35.78)	19.273	<0.01
Ⅲ度菌群失调[例(%)]	1(1.25)	2(2.94)	11(10.09)	9.252	0.009

表2 3组门水平优势菌群比较($\bar{x}$±s)

肠道菌群	健康组(n=80)	母乳性黄疸组(n=68)	胆汁淤积性黄疸组(n=109)	$F$ 值	P值
拟杆菌门	19.69±11.24	4.87±3.58^*	33.21±21.52^*#	18.671	<0.01
厚壁菌门	16.37±13.72	43.57±15.82^*	49.63±16.73^*#	11.714	0.003
变形菌门	47.89±15.59	59.63±18.41^*	48.24±16.27^#	13.848	0.002
放线菌门	31.22±13.56	22.48±9.92^*	8.57±6.64^*#	15.874	<0.01

表2 3组门水平优势菌群比较($\bar{x}$±s)

肠道菌群	健康组(n=80)	母乳性黄疸组(n=68)	胆汁淤积性黄疸组(n=109)	$F$ 值	P值
拟杆菌门	19.69±11.24	4.87±3.58^*	33.21±21.52^*#	18.671	<0.01
厚壁菌门	16.37±13.72	43.57±15.82^*	49.63±16.73^*#	11.714	0.003
变形菌门	47.89±15.59	59.63±18.41^*	48.24±16.27^#	13.848	0.002
放线菌门	31.22±13.56	22.48±9.92^*	8.57±6.64^*#	15.874	<0.01

表3 3组属水平优势菌群丰度的比较($\bar{x}$±s)

菌属	健康组(n=80)	母乳性黄疸组(n=68)	胆汁淤积性黄疸组(n=109)	$F$ 值	P值
双歧杆菌	8.94±0.89	7.23±0.92^*	6.97±0.53^*#	4.512	0.024
大肠杆菌	6.37±1.13	6.22±1.09	8.09±0.91^*#	3.916	0.039
乳酸杆菌	5.61±0.89	5.72±0.86	4.67±1.21^*#	3.385	0.041
肠球菌	5.29±0.82	5.32±0.79	7.93±0.75^*#	4.116	0.027
B/E值	1.39±0.22	1.15±0.23^*	0.87±0.14^*#	5.742	0.011

表3 3组属水平优势菌群丰度的比较($\bar{x}$±s)

菌属	健康组(n=80)	母乳性黄疸组(n=68)	胆汁淤积性黄疸组(n=109)	$F$ 值	P值
双歧杆菌	8.94±0.89	7.23±0.92^*	6.97±0.53^*#	4.512	0.024
大肠杆菌	6.37±1.13	6.22±1.09	8.09±0.91^*#	3.916	0.039
乳酸杆菌	5.61±0.89	5.72±0.86	4.67±1.21^*#	3.385	0.041
肠球菌	5.29±0.82	5.32±0.79	7.93±0.75^*#	4.116	0.027
B/E值	1.39±0.22	1.15±0.23^*	0.87±0.14^*#	5.742	0.011

表4 血清胆红素水平与门水平优势菌群相关性分析

指标	拟杆菌门		厚壁菌门		变形菌门		放线菌门
指标	r	P	r	P	r	P	r	P
ALT	0.219	0.016	0.252	0.009	0.072	0.626	-0.217	0.025
TBIL	0.198	0.021	0.323	0.01	0.027	0.718	-0.329	0.01
DBIL	0.203	0.009	0.214	0.018	0.104	0.157	-0.179	0.042
DBIL/TBIL	0.167	0.035	0.186	0.029	0.096	0.312	-0.184	0.038

表5 血清胆红素水平与属水平优势菌群相关性分析

指标	双歧杆菌		乳酸杆菌		大肠杆菌		肠球菌		B/E值
指标	r	P	r	P	r	P	r	P	r	P
ALT	0.087	0.657	0.069	0.063	0.026	0.911	0.039	0.812	0.062	0.731
TBIL	-0.475	0.023	0.214	0.272	0.492	0.005	0.412	0.035	-0.337	0.014
DBIL	-0.462	0.009	-0.114	0.583	-0.262	0.217	-0.031	0.887	-0.407	0.011
DBIL/TBIL	-0.438	0.016	-0.129	0.376	-0.398	0.011	-0.394	0.027	-0.439	0.006

参考文献 19

[1]	田淑萍, 布如飞, 黄洁蕾. 新生儿早发型母乳性黄疸与生理性黄疸的临床分析[J]. 宁夏医学杂志, 2016, 38(12):1247-1248.
[2]	温美莲, 陈浩. 抚触护理联合熊去氧胆酸治疗新生儿胆汁淤积性黄疸的临床观察[J]. 中国医学创新, 2017, 14(17):79-82.
[3]	黄敏辉, 陈召金, 叶玉婷. 妊娠期肝内胆汁淤积症患者血清胆汁酸水平与新生儿黄疸的关系[J]. 广州医科大学学报, 2020, 48(4):16-19.
[4]	Kim JR, Hwang JY, Yoon HM, et al. Risk estimation for biliary atresia in patients with neonatal cholestasis: Development and validation of a risk score[J]. Radiology, 2018, 288(1):262-269. doi: 10.1148/radiol.2018172390 pmid: 29634437
[5]	李雁彬, 周伟, 袁伟明, 等. 严重高胆红素血症新生儿肠道菌群构成情况及对胆红素脑损伤的影响[J]. 中华实用儿科临床杂志, 2018, 33(2): 103-107.
[6]	李亚璇, 莫茜, 孙建华, 等. 母乳喂养新生儿早期重度高胆红素血症肠道菌群特征研究[J]. 临床儿科杂志, 2019, 37(5):351-355.
[7]	Fawaz R, Baumann U, Ekong U, et al. Guideline for the evaluation of cholestatic jaundice in infants: Joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition[J]. J Pediatr Gastroenterol Nutr, 2017, 64(1):154-168. doi: 10.1097/MPG.0000000000001334 URL
[8]	Bruyne RD, Biervliet SV, Velde SV, et al. Clinical practice: neonatal cholestasis[J]. Eur J Pediatr, 2011, 170(3):279-284. doi: 10.1007/s00431-010-1363-8 pmid: 21249394
[9]	Lane E, Murray KF. Neonatal cholestasis[J]. Pediatr Clin North Am, 2017, 64(3):621-639. doi: 10.1016/j.pcl.2017.01.006 URL
[10]	Han S, Yang JD, Sinn DH, et al. Higher bilirubin levels of healthy living liver donors are associated with lower posttransplant hepatocellular carcinoma recurrence[J]. Transplantation, 2016, 100(9) :1933-1938. doi: 10.1097/TP.0000000000001293 pmid: 27362316
[11]	刘艳辉, 刘丽娟. 茵栀黄颗粒联合双歧杆菌四联活菌片对早产儿肠道菌群及胆红素水平的影响[J]. 中医学报, 2016(9):1401-1404.
[12]	Hernández-Rodríguez D, Vásquez-Aguilar AA, Serio-Silva JC, et al. Molecular detection of Bifidobacterium spp. in faeces of black howler monkeys (Alouatta pigra)[J]. J Med Primatol, 2019, 48(2):99-105. doi: 10.1111/jmp.12395 pmid: 30520095
[13]	张国风. 母乳性黄疸的鉴别诊断[J]. 中国实用儿科杂志, 2001, 16(3):131-132.
[14]	于宏, 程清模. 母乳性黄疸的发病与母乳喂养相关因素的分析[J]. 中华临床医药杂志, 2001, 2(5):37-38.
[15]	Dethlefsen L, Eckburg PB, Bik EM, et al. Assembly of the human intestinal microbiota[J]. Trends Ecol Evol, 2006, 21(9):517-523. pmid: 16820245
[16]	栗冲, 王硕, 张志华. 抗生素与肠道微生态的关系[J]. 临床荟萃, 2021, 36(4):374-378.
[17]	Burkholder R, Martinez M, Chapa-Rodriguez A. An Unusual Cause of Neonatal Cholestasis: 2403[J]. Am J Gastroenterol, 2018, 113(21):1341.
[18]	Amy G, Feldman, Ronald J, et al. Neonatal cholestasis: emerging molecular diagnostics and potential novel therapeutics[J]. Nat Rev Gastroenterol Hepato, 2019, 16(6):346-360. doi: 10.1038/s41575-019-0132-z URL
[19]	Wu G, Chen X, Cui N, et al. Preventive effect of bifidobacterium supplementation on neonatal cholestasis in preterm neonates with very low birth weight[J]. Gastroenterol Res Pract, 2020, 20 (3):1-7.