牛奶蛋白过敏婴儿肠道菌群动态变化特点

doi:10.12372/jcp.2022.21e1524

摘要/Abstract

摘要：

目的动态监测分析牛奶蛋白过敏（CMPA）患儿临床治疗过程中牛奶蛋白耐受和肠道菌群变化情况。方法选择2020年9月至2021年3月门诊就诊的CMPA儿童50例为CMPA组，选取同期健康体检儿童20例为对照组，比较两组肠道菌群差异。结果 CMPA组男21例、女29例，中位月龄4.00（2.00~4.75）月。对照组男12例、女8例，中位月龄4.00（3.00~5.00）月。CMPA组的Shannon指数及Shannoneven指数较对照组增高，差异有统计学意义（P<0.05）。Anosim检验结果显示两组样本间群落组成差异有统计学意义（P<0.01）。CMPA组放线菌门的相对丰度明显降低，厚壁菌门相对丰度升高。随访第1、3、6个月CMPA组儿童治疗及转归情况发现，至6个月时共38例患儿建立免疫耐受，另12例仍存在CMPA。随访半年后，耐受组较过敏组的放线菌纲、双歧杆菌属的相对丰度升高。CMPA耐受组儿童丰度逐渐升高的物种有双歧杆菌属（P<0.01）、布劳特菌属（P<0.01）、瘤胃球菌属（P<0.01）和普氏粪植杆菌属（P<0.01），除双歧杆菌属为产乙酸菌外，其他菌种均为产丁酸菌。结论 CMPA患儿与健康儿童肠道菌群不同。在建立免疫耐受过程中，CMPA患儿肠道中双歧杆菌及产丁酸菌群相对丰度升高。

关键词: 牛奶蛋白过敏, 肠道菌群, 16S rRNA高通量测序, 双歧杆菌

Abstract:

Objective To dynamically monitor and analyze infants with cow’s milk protein allergy (CMPA), milk protein tolerance and changes in gut microbiome during clinical treatment. Methods Fifty infants with CMPA attended the pediatric outpatient clinic were selected as the CMPA group, and 20 infants underwent health checkups were selected as the healthy control groupat the Child Health Development Center of Peking University Third Hospital from September 2020 to March 2021. The differences in gut microbiome between the two groups were compared. Results There were 50 patients in the CMPA group, including 21 males and 29 females, with a median age of 4 months. The control group consisted of 20 cases, of 12 males and 8 females, with a median age of 4 months. There were no statistically significant differences between the CMPA group and the control group in terms of age inmonths, sex, birth mass, mode of delivery, and feeding mode (all P>0.05). The baseline data of the children in the two groups were comparable. Follow-up of treatment and regression of children in the CMPA group at months 1, 3, and 6 revealed that a total of 38 children had established immune tolerance by 6 months, and 12 others still had CMPA. The Shannon index and Shannoneven index were statistically higher in the CMPA group compared with the control group (P<0.05), and the Anosim test showed statistically significant differences in community composition between the two sample groups (R=0.26, P=0.001). The relative abundance of Actinobacteria was significantly lower in the CMPA group. The relative abundance of Firmicutes was higher in the tolerant group than in the allergic group after six months of follow-up. During the treatment of CMPA-tolerant infants, species with progressively higher abundance were observed for Bifidobacterium (P<0.01), Blautia (P<0.01), Ruminococcus (P<0.01) and Faecalibacterium (P<0.01). Except for Bifidobacterium, all other species were known as butyrate producers. Conclusion The gut microbiome of children with CMPA differs from that of healthy children. The relative abundance of Bifidobacterium and butyrate-producers microbiome in the intestine of children with CMPA was increased during the establishment of immune tolerance.

Key words: cow’s milk protein allergy, gut microbiome, 16S rRNA high-throughput sequencing, Bifidobacterium

李心悦, 王硕, 张华, 李在玲. 牛奶蛋白过敏婴儿肠道菌群动态变化特点[J]. 临床儿科杂志, 2022, 40(11): 831-838.

LI Xinyue, WANG Shuo, ZHANG Hua, LI Zailing. Characteristics of dynamic changes in the gut microbiome of infants with cow's milk protein allergy[J]. Journal of Clinical Pediatrics, 2022, 40(11): 831-838.

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项目	对照组(n=20)	CMPA组(n=50)	统计量	P
月龄[M(P₂₅~P₇₅)]/月	4.00(3.00~5.00)	4.00(2.00~4.75)	Z=0.52	0.602
出生体重(x±s)/kg	3.20±0.37	3.23±0.40	t=0.30	0.768
男性[n(%)]	12(60.0)	21(42.0)	χ²=1.86	0.173
自然分娩[n(%)]	11(55.0)	32(64.0)	χ²=0.49	0.485
喂养方式[n(%)]			-	0.261¹⁾
母乳	12(60.0)	29(58.0)
奶粉	2(10.0)	1(2.0)
混合	6(30.0)	20(40.0)

组别	Ace指数	Chao指数	Shannon指数	Shannoneven指数	Pd指数
对照组	98.63±45.93	99.78±48.35	1.44(0.94~1.96)	0.35(0.24~0.45)	7.96(5.93~9.06)
CMPA组	117.50±40.93	109.49±35.95	1.91(1.50~2.13)	0.43(0.37~0.48)	8.27(6.10~12.41)
统计量	t=1.48	t=0.79	Z=2.00	Z=2.09	Z=1.03
P	0.145	0.434	0.041	0.037	0.302