光疗对于黄疸新生儿肠道菌群及耐药基因的影响分析

doi:10.12372/jcp.2022.21e0643

Abstract

Abstract:

Objective To analyze the changes of intestinal microflora and drug-resistant genes in jaundiced neonates receiving phototherapy, and to explore its clinical significance. Methods Metagenomic sequencing was used to analyze the changes of intestinal flora and drug-resistant genes in neonates with jaundice after phototherapy. Results There was no significant difference in the α- and β-diversity of the intestinal microflora abundance after 24 and 48 hours of phototherapy (P>0.05). At the species level, the relative abundance of some species increased, including Clostridium bolteae, Enterococcus faecium and Streptococcus thermophilus (P<0.01). The intestinal flora of jaundiced neonates carried a large number of drug-resistant genes, a total of 242 genes, mainly tetracycline, β-lactams, macrolides, sulfonamides and aminoglycosides, and more resistant genes of Escherichia coli were also found. With the prolongation of phototherapy time, some drug resistance genes changed significantly. The main increased resistance genes were β-lactam resistance gene (CTX-M-14), aminoglycoside resistance gene (aadA2), tetracycline resistance gene [tet(59)], efflux pump gene (efmA), quinolone resistance gene (QnrS2), carbapenemase gene (OXA-347) and sulfonamide resistance gene (dfrA1), while the abundance of mgrA in Staphylococcus aureus decreased after phototherapy, and the differences were significant (P<0.05). After 48 hours of phototherapy, the species abundance of the following intestinal microflora showed a significant positive correlation with drug resistance genes: Clostridium and aminoglycoside resistance gene [APH(3')-Ia], Bacteroides uniformis and β-lactam resistance gene (CfxA6), Enterobacter cloacae and fosfomycin resistance gene (UhpT), Streptococcus parahaemolyticus and macrolide resistance gene (mefA) (P<0.01); while the species abundance of Enterococcus faecalis was negatively correlated with aminoglycoside resistance gene [ANT(2") -Ia] (P<0.01). Conclusions Phototherapy can change the relative abundance of some bacterial species in the intestinal microflora of neonates and significantly increase the abundance of some drug-resistant genes. Whether the disruption of bacterial homeostasis is related to the adverse reactions of phototherapy and its clinical significance needs further study.

Key words: jaundice, phototherapy, intestinal microflora, drug-resistant gene, neonate

ZHANG Kun, FAN Sainan, ZHENG Fang, ZHANG Jiahui, WU Zhimin, LYU Anping, MA Yanan, FANG Xiaohui, ZHANG Jinping. The effect of phototherapy on intestinal flora and drug-resistant genes in jaundiced neonates[J].Journal of Clinical Pediatrics, 2022, 40(6): 436-441.

Figures/Tables 6

References 25

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菌种	相对丰度			H值	P
菌种	光疗前	光疗24 h后	光疗48 h后	H值	P
梭状芽孢杆菌/×10^–2	10.0(5.0~81.0)	106.0(85.0~210.0)	207.7(114.2~524.6)	9.94	0.008
粪肠球菌	3.7(2.1~7.4)	4.7(2.2~9.7)	5.4 (3.3~12.0)	8.95	0.005
类杆菌	0.2(0.1~0.3)	0.2(0.1~0.4)	1.0(0.5~ 2.4)	7.26	0.034
阴沟肠杆菌	1.0(0.8~4.7)	3.0(1.0~7.2)	3.4(1.7~9.0)	8.45	0.020
巴氏链球菌	0.1(0.1~0.5)	1.7(0.8~3.3)	2.4(1.2~6.1)	7.59	0.035
嗜热链球菌/×10^–2	1.0(0.4~10.0)	3.6(1.4~19.8)	1.2(0.5~2.9)	14.59	<0.001
不动杆菌属
未分类/×10^–3	0.4(0.1~0.9)	1.3(0.7~9.6)	10.0(3.0~96.0)	6.60	0.034
丙酸棒杆菌/×10^–3	0.4(0.1~0.9)	0.1(0.1~0.8)	0.0(0.0~0.0)	4.57	0.041
直肠真杆菌/×10^–3	0.5(0~1.0)	0.9(0.2~1.2)	5.0(7.0~96.0)	9.26	0.015
痤疮丙酸杆菌/×10^–4	3.0(1.2~8.6)	0.9(0.3~3.6)	0.0(0.0~0.0)	6.60	0.037

耐药基因	光疗前	光疗24 h后	光疗48 h后	H值	P
QnrS2/×10^–3	10.0(2.0~63.3)	15.2(4.0~100.0)	20.0(30.0~26.0)	10.55	0.005
CTX-M-14	0.0(0.0~0.1)	3.3(2.6~8.7)	9.0(4.1~15.3)	9.26	0.001
dfrA1/×10^–2	50.0(5.0~90.1)	19.9(16.0~98.0)	57.7(32.2~191.0)	12.14	0.002
aadA2	0.0(0.0~0.0)	1.0(0.2~2.4)	4.7(2.6~8.3)	8.25	0.016
efmA	0.1(0.0~0.4)	0.3(0.3~1.0)	1.3(0.9~3.3)	8.25	0.013
tet(59)/×10^-2	29.9(20.1~40.1)	40.0(30.1~80.2)	85.1(50.0~120.5)	8.69	0.013
OXA-347	0.0(0.0~0.1)	0.1(0.0~0.2)	0.1(0.1~0.4)	5.45	0.031
mgrA	7.1(4.3~15.6)	5.9(2.2~9.7)	1.8(0.6~3.3)	6.09	0.048

耐药基因	菌种	相关系数	P
APH(3')-Ia	梭状芽孢杆菌	0.685	<0.001
ANT(2'')-Ia	粪肠球菌	–0.406	0.002
CfxA6	单形拟杆菌	0.372	0.005
UhpT	阴沟肠杆菌	0.591	<0.001
mefA	副血链球菌	0.403	0.002

The effect of phototherapy on intestinal flora and drug-resistant genes in jaundiced neonates

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