炎症性肠病患儿血清AGR2、TMAO水平及与肠道菌群的相关性

doi:10.11958/20241934

天津医药 ›› 2025, Vol. 53 ›› Issue (2): 156-160.doi: 10.11958/20241934

炎症性肠病患儿血清AGR2、TMAO水平及与肠道菌群的相关性

党青华¹(), 谷丽芳²^,^△(), 张先霞¹, 张毅¹, 曾宁³

1 西安国际医学中心医院儿内科（邮编714000）
2 西安国际医学中心医院儿童保健科（邮编714000）
3 西安国际医学中心医院医学检验科（邮编714000）

收稿日期:2024-11-21 修回日期:2024-12-17 出版日期:2025-02-15 发布日期:2025-02-26
通讯作者: ^△ E-mail：535239746@qq.com
作者简介:党青华（1978），女，副主任医师，主要从事儿童消化系统疾病方面研究。E-mail：q574132yk@163.com

Serum AGR2 and TMAO levels and their correlation with gut microbiota in children with inflammatory bowel disease

DANG Qinghua¹(), GU Lifang²^,^△(), ZHANG Xianxia¹, ZHANG Yi¹, ZENG Ning³

1 Department of Pediatric Internal Medicine, Xi 'an International Medical Center Hospital, Xi 'an 714000, China
2 Department of Child Healthcare, Xi 'an International Medical Center Hospital, Xi 'an 714000, China
3 Department of Medical Laboratory, Xi 'an International Medical Center Hospital, Xi 'an 714000, China

Received:2024-11-21 Revised:2024-12-17 Published:2025-02-15 Online:2025-02-26
Contact: ^△ E-mail：535239746@qq.com

党青华, 谷丽芳, 张先霞, 张毅, 曾宁. 炎症性肠病患儿血清AGR2、TMAO水平及与肠道菌群的相关性[J]. 天津医药, 2025, 53(2): 156-160.

DANG Qinghua, GU Lifang, ZHANG Xianxia, ZHANG Yi, ZENG Ning. Serum AGR2 and TMAO levels and their correlation with gut microbiota in children with inflammatory bowel disease[J]. Tianjin Medical Journal, 2025, 53(2): 156-160.

摘要/Abstract

摘要：

目的探讨炎症性肠病（IBD）患儿血清前梯度同源蛋白2（AGR2）、氧化三甲胺（TMAO）水平与肠道菌群的关系。方法选取145例IBD患儿为观察组，根据疾病类型分为溃疡性结肠炎组64例和克罗恩病组81例，同时纳入于本院进行健康体检的儿童140例作为对照组。采用酶联免疫吸附试验（ELISA）检测血清AGR2、TMAO水平。分别采用改良梅奥（Mayo）评分和克罗恩病活动指数（CDAI）评分评估溃疡性结肠炎和克罗恩病的疾病活动度，根据疾病活动度分为活动期组（75例）和缓解期组（70例）。采集患儿粪便样本进行肠道菌群培养鉴定和计数。绘制受试者工作特征（ROC）曲线分析血清AGR2、TMAO水平对溃疡性结肠炎和克罗恩病的诊断价值。Pearson检验分析血清AGR2、TMAO水平与肠道菌群的相关性。Logistic回归分析血清AGR2、TMAO水平与IBD患儿疾病分期的关系。结果溃疡性结肠炎组、克罗恩病组血清AGR2水平低于对照组，TMAO水平高于对照组（P<0.05）。血清AGR2、TMAO水平单独和联合诊断溃疡性结肠炎的曲线下面积（AUC）为0.835、0.836、0.896，诊断克罗恩病的AUC为0.859、0.864、0.964。活动期组血清AGR2水平及乳酸杆菌、双歧杆菌数量低于缓解期组，血清TMAO水平及大肠杆菌、肠球菌、幽门螺杆菌、链球菌数量高于缓解期组（P<0.05）。IBD患儿血清AGR2水平与乳酸杆菌、双歧杆菌数量呈正相关，与大肠杆菌、肠球菌、幽门螺杆菌、链球菌数量呈负相关（P<0.05）；血清TMAO水平与乳酸杆菌、双歧杆菌数量呈负相关，与大肠杆菌、肠球菌、幽门螺杆菌、链球菌数量呈正相关（P<0.05）。血清AGR2水平降低、TMAO水平升高是IBD患儿疾病进展为活动期的危险因素（P<0.05）。结论血清AGR2、TMAO联合可有效诊断溃疡性结肠炎和克罗恩病，且对克罗恩病诊断价值更高，二者表达异常可能通过影响肠道菌群结构变化参与IBD疾病进展。

关键词: 炎性肠疾病, Crohn病, 结肠炎, 溃疡性, 儿童, 前梯度同源蛋白2, 氧化三甲胺, 肠道菌群

Abstract:

Objective To explore the relationship between serum levels of anterior gradient 2 (AGR2) and trimethylamine N-oxide (TMAO) and gut microbiota in children with inflammatory bowel disease (IBD). Methods A total of 145 IBD children were selected as the observation group, and children were divided into the ulcerative colitis group (64 cases) and the Crohn's disease group (81 cases) according to the disease type. Meanwhile, 140 healthy children underwent physical examination in our hospital were included as the control group. Serum AGR2 and TMAO levels were detected by enzyme-linked immunosorbent assay (ELISA). The disease activity of ulcerative colitis and Crohn's disease were evaluated using the modified Mayo score and the Crohn's Disease Activity Index (CDAI) score, and patients were divided into the active group (75 cases) and the remission group (70 cases) according to the disease activity. Fecal samples were collected for identification and count of intestinal flora. Receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic value of serum AGR2 and TMAO levels in ulcerative colitis and Crohn's disease. The correlation between serum AGR2 and TMAO levels and intestinal flora was analyzed by Pearson test. Logistic regression was used to analyze the relationship between serum AGR2 and TMAO levels and the disease stage of children with IBD. Results The serum AGR2 level was lower in the ulcerative colitis group and the Crohn's disease group than that in the control group, and the serum TMAO level was higher than that in the control group (P<0.05). The areas under the curve (AUC) of serum AGR2 and TMAO levels were 0.835, 0.836 and 0.896 for diagnosis of ulcerative colitis alone and 0.859, 0.864 and 0.964 for diagnosis of Crohn's disease. The serum AGR2 level and numbers of lactobacillus and bifidobacterium were significantly lower in the active group than those in the remission group, and the serum TMAO level and numbers of Escherichia coli, enterococcus, Helicobacter pylori and streptococcus were significantly higher in the active group than those in the remission group (P<0.05). Serum AGR2 levels in IBD children were positively correlated with numbers of lactobacillus and bifidobacterium, and negatively correlated with numbers of Escherichia coli, Enterococcus, Helicobacter pylori and streptococcus (P<0.05). Serum TMAO level was negatively correlated with numbers of lactobacillus and bifidobacterium, and positively correlated with numbers of Escherichia coli, Enterococcus, Helicobacter pylori and streptococcus (P<0.05). The decreased serum AGR2 level and the increased TMAO level were risk factors for the disease progression to active stage in children with IBD (P<0.05). Conclusion The combination of serum AGR2 and TMAO can effectively diagnose ulcerative colitis and Crohn's disease, and it is more valuable in the diagnosis of Crohn's disease. Abnormal expression of both may participate in the progression of IBD disease by affecting changes in gut microbiota structure.

Key words: inflammatory bowel diseases, Crohn disease, colitis, ulcerative, child, anterior gradient 2, trimethylamine N-oxide, gut microbiota

中图分类号:

R725.74

图/表 9

参考文献 20

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组别	n	AGR2/（ng/L）	TMAO/（μmol/L）
对照组	140	382.75±97.84	4.41±1.12
溃疡性结肠炎组	64	266.24±69.33^a	6.08±1.56^a
克罗恩病组	81	260.81±71.45^a	6.12±1.50^a
F		70.364^＊＊	56.674^＊＊

组别	n	AGR2/（ng/L）	TMAO/（μmol/L）
对照组	140	382.75±97.84	4.41±1.12
溃疡性结肠炎组	64	266.24±69.33^a	6.08±1.56^a
克罗恩病组	81	260.81±71.45^a	6.12±1.50^a
F		70.364^＊＊	56.674^＊＊

指标	敏感度/%	特异度/%	截断值	AUC（95%CI）
AGR2	79.73	72.15	333.33 ng/L	0.835（0.776~0.894）
TMAO	70.38	86.47	5.08 μmol/L	0.836（0.772~0.901）
联合	87.51	82.16		0.896（0.842~0.950）

指标	敏感度/%	特异度/%	截断值	AUC（95%CI）
AGR2	79.73	72.15	333.33 ng/L	0.835（0.776~0.894）
TMAO	70.38	86.47	5.08 μmol/L	0.836（0.772~0.901）
联合	87.51	82.16		0.896（0.842~0.950）

指标	敏感度/%	特异度/%	截断值	AUC（95%CI）
AGR2	88.93	76.43	304.35 ng/L	0.859（0.809~0.908）
TMAO	76.51	85.57	5.29 μmol/L	0.864（0.812~0.917）
联合	90.12	92.12		0.964（0.941~0.988）

炎症性肠病患儿血清AGR2、TMAO水平及与肠道菌群的相关性

Serum AGR2 and TMAO levels and their correlation with gut microbiota in children with inflammatory bowel disease

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组别	n	AGR2/（ng/L）	TMAO/（μmol/L）
缓解期组	70	304.32±78.12	5.50±1.32
活动期组	75	224.84±56.09	6.66±1.61
t		6.994^＊＊	4.741^＊＊

组别	n		大肠杆菌		肠球菌	幽门螺杆菌
缓解期组	70		6.40±1.12		5.42±0.61	6.12±0.71
活动期组	75		8.22±1.53		7.89±1.35	8.86±0.94
t			8.186^＊＊		14.233^＊＊	20.001^＊＊
组别		链球菌		乳酸杆菌			双歧杆菌
缓解期组		5.03±0.76		7.10±1.16			6.96±1.07
活动期组		7.45±0.81		5.54±0.71			5.38±0.66
t		18.532^＊＊		9.583^＊＊			10.532^＊＊

菌群	AGR2	TMAO
大肠杆菌	-0.507^＊＊	0.525^＊＊
肠球菌	-0.533^＊＊	0.519^＊＊
幽门螺杆菌	-0.529^＊＊	0.527^＊＊
链球菌	-0.512^＊＊	0.536^＊＊
乳酸杆菌	0.542^＊＊	-0.541^＊＊
双歧杆菌	0.531^＊＊	-0.535^＊＊

变量	β	SE	Wald χ²	P	OR（95%CI）
AGR2	-0.205	0.072	8.072	0.005	0.815（0.708~0.939）
TMAO	0.992	0.319	9.673	0.002	2.697（1.443~5.040）
常数项	-4.875	1.153	6.724	<0.001	0.004

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