儿童过敏性紫癜口腔菌群及其代谢产物特征

doi:10.3969/j.issn.1006-5725.2024.09.011

摘要/Abstract

摘要：

目的探讨儿童过敏性紫癜（HSP）的口腔菌群及其代谢产物特征，阐明过敏性紫癜发病的机制。方法纳入合格受试者3组，其中HSP组20例，紫癜性肾炎（HSPN）组20例，对照组20例。对各组的唾液进行16S rRNA测序和代谢组学分析，分析差异性菌群与差异性代谢物之间的相关性。结果（1）与对照组相比，HSPN组丰富度和多样性差异有统计学意义（P < 0.05），HSP组丰富度和多样性差异无统计学意义（P > 0.05）。与HSP组相比，HSPN组丰富度和多样性显著升高（P < 0.05）。其中属水平上，各组中链球菌占比最高。与对照组相比，HSP组无显著性相关菌属，HSPN组假单胞菌属和副拟杆菌属显著增高（P < 0.05）。与HSP组相比，HSPN组假单胞菌属和副拟杆菌属相对丰度显著升高（P < 0.05）。（2）与对照组相比，HSPN组有12种差异性代谢产物，涉及苯丙氨酸代谢等9种代谢途径；HSP组差异无统计学意义代谢产物，无代谢通路。与HSP组相比，HSPN组有15种差异性代谢产物，涉及苯丙氨酸代谢等9种代谢途径。（3）HSPN组与对照组中假单胞菌属、副拟杆菌属与苯丙氨酸代谢途径产物呈负相关。HSPN组与HSP组中假单胞菌属、副拟杆菌属与苯丙氨酸代谢途径产物呈负相关。口腔中参与苯丙氨酸代谢的代谢产物为2-羟基肉桂酸、苯丙酮酸、N-乙酰基-L-苯丙氨酸。结论链球菌属、假单胞菌属、副拟杆菌属可能作为HSPN发病的触发因素之一，苯丙氨酸代谢可能是HSPN的发病过程中的通路之一。相比于HSP患儿，HSPN患儿口腔菌群失调更加明显，代谢产物差异性更强。

关键词: 过敏性紫癜, 16S rRNA, 代谢组学, 口腔, 儿童

Abstract:

Objective To study and compare the oral microbiota and metabolites of children with Henoch Schonlein purpura（HSP） to identify specific microbiota and metabolites related to this disease and elucidate the pathogenesis of HSP. Methods Three groups of qualified subjects were included， including 20 in the HSP group， 20 in the HSP nephritis （HSPN） group， and 20 in the control group. Perform high?throughput 16S rRNA sequencing and metabolic profiling of saliva from each group to analyze the correlation between differential microbiota and differential metabolites. Results （1） Compared with the control group， there was a significant difference in richness and diversity in the HSPN group （P < 0.05）. At the same time， there was no significant difference in richness and diversity in the HSP group （P > 0.05）. Compared with the HSP group， the abundance， and diversity of the HSPN group were significantly increased （P < 0.05）. At the genus level， the proportion of Streptococcus in each group is the highest. Compared with the control group， there was no significant correlation between the HSP group and the genus of bacteria. In contrast， the HSPN group showed a significant increase in the genera of Pseudomonas and Parabacteroides （P < 0.05）. Compared with the HSP group， the abundance of Pseudomonas and Parabacteroides in the HSPN group was significantly increased （P < 0.05）. （2） Compared with the control group， the HSPN group had 12 differential metabolites involving nine metabolic pathways， such as phenylalanine metabolism； There was no significant difference in metabolites and no metabolic pathway in the HSP group. Compared with the HSP group， the HSPN group has 15 differential metabolites involving nine metabolic pathways， such as phenylalanine metabolism. （3） In the HSPN and control groups， Pseudomonas and Parabacteroides negatively correlated with Phenylalanine metabolic pathway products. In the HSPN and HSP groups， Pseudomonas， Parabacteroides， and Phenylalanine metabolic pathway products were negatively correlated. The metabolites involved in phenylalanine metabolism in the oral cavity are 2?hydroxycinnamic acid， Phenylpyruvic acid， and N?acetyl?L?phenylalanine. Conclusion There is a significant difference between HSPN and HSP children and healthy children. Streptococcus， Pseudomonas， and Parabacteroides may be one of the trigger factors of HSPN， and Phenylalanine metabolism may be one of the pathways in the pathogenesis of HSPN. Children with HSPN have a more pronounced imbalance in oral microbiota and greater differences in metabolic products than children with HSP.

Key words: henoch schonlein purpura, 16S rRNA, metabolomics, oral cavity, children

中图分类号:

R554⁺.6

王晴雯,张淑雅,熊维霖,胡晓磊,李紫薇,郭庆寅. 儿童过敏性紫癜口腔菌群及其代谢产物特征[J]. 实用医学杂志, 2024, 40(9): 1244-1250.

Qingwen WANG,Shuya ZHANG,Weilin XIONG,Xiaolei HU,Ziwei LI,Qingyin. GUO. Characteristics of oral flora and its metabolites in children with henoch⁃schonlein purpura[J]. The Journal of Practical Medicine, 2024, 40(9): 1244-1250.

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项目	对照组（n = 20）	HSP组（n = 20）	HSPN组（n = 19）	统计值	P值
性别（例）				0.210	0.895
男	14	13	11
女	6	7	8
年龄（岁）	8.10 ± 1.89	7.35 ± 2.16	8.74 ± 2.28	1.931	0.132
身高（cm）	132.25 ± 7.23	127.15 ± 10.70	130.37 ± 8.25	1.446	0.236
体质量（kg）	30.75 ± 4.89	28.65 ± 4.83	31.79 ± 8.54	1.364	0.260

组别	Chao1	Observed_species	Simpson
HSPN组	880.85 ± 420.40	686.68 ± 328.06	0.897 ± 0.059
HSP组	478.94 ± 253.91	387.40 ± 153.15	0.930 ± 0.018
健康对照组	508.97 ± 256.70	424.55 ± 195.32	0.937 ± 0.022

组别	R值	P值
HSPN组 VSHSP组	0.304 9	0.001
HSPN组 VS 健康对照组	0.297 5	0.001
HSP组 VS健康对照组	0.040 8	0.089

差异性代谢产物	变化	代谢途径
N-乙酰糠酸酯	-	—
腺苷	-	泛酸和CoA生物合成
琥珀酸	-	丙酸代谢；丁酸代谢
苯丙氨酸	-	苯丙氨酸代谢
γ-氨基丁酸	-	精氨酸和脯氨酸代谢
壬二酸	+	—
N-乙酰-L-苯丙氨酸	-	苯丙氨酸代谢
L-缬氨酸	-	丙酸代谢
苯丙酮酸	-	苯丙氨酸代谢
2-羟基戊二酸	+	柠檬酸循环
2-羟基肉桂酸	-	苯丙氨酸代谢
N、 N-二甲基鸟苷	-	—
β-羟基丙酮酸	+	乙醛酸和二羧酸代谢
甲羟戊酸	-	萜类骨架生物合成
生物素	+	生物素代谢

差异性代谢产物	变化	代谢途径
2-羟基肉桂酸	-	苯丙氨酸代谢
苯丙酮酸	-	苯丙氨酸代谢
L-缬氨酸	-	缬氨酸、亮氨酸和异亮氨酸生物合成；丙氨酸、天冬氨酸和谷氨酸代谢
N-乙酰-L-苯丙氨酸	-	苯丙氨酸代谢
2-羟基-2-甲基丁酸	-	-
腺苷	-	泛酸和CoA生物合成；嘌呤代谢
甲羟戊酸	-	萜类骨架生物合成
N、N-二甲基鸟苷	-	-
2-羟基戊二酸	+	柠檬酸循环
β-羟基丙酮酸	+	乙醛酸和二羧酸代谢
瓜氨酸	-	精氨酸和脯氨酸代谢
γ-氨基丁酸	-	精氨酸和脯氨酸代谢