Correlation between serum insulin-like growth factor-1 expression and characteristics of gut microbiota in children with cerebral palsy accompanied by growth retardation
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摘要:
目的 探讨脑性瘫痪(简称“脑瘫”)伴生长发育迟缓儿童血清胰岛素样生长因子1(IGF-1)表达、肠道菌群特征及相关性，为促进脑瘫伴生长发育迟缓儿童身心健康提供参考依据。 方法 2022年6月—2023年6月随机选取广州市某福利院的3~14岁112名脑瘫儿童，按照WHO标准是否生长发育迟缓分为脑瘫伴生长发育迟缓组(80名)和脑瘫伴生长发育正常组(32名)，并选取同院生活的健康儿童32名为对照组；对3组儿童进行血清IGF-1测定，并用16S rDNA测序技术测定肠道菌群，探究3组儿童IGF-1表达特点、肠道菌群群落组成和差异特征及相关性。 结果 对3组儿童血清IGF-1水平进行比较，脑瘫伴生长发育迟缓组[97.70(66.35，139.50)ng/mL]、脑瘫伴生长发育正常组[149.00(68.30，233.00)ng/mL]均低于健康对照组[169.90(118.75，293.80)ng/mL]，差异有统计学意义(H=20.13，P < 0.05)。脑瘫伴生长发育迟缓组和脑瘫伴生长发育正常组肠道菌群Alpha多样性均高于健康对照组[Chao指数(482.50，489.90，396.10)、Shannon指数(6.29，6.44，5.89)和Simpson指数(0.97，0.97，0.96)](H值分别为17.20，7.01，6.41，P值均 < 0.05)。IGF-1与Eubacterium coprostanoligenes group、罕见小球菌属相对丰度均呈正相关(r值分别为0.38，0.33，P值均＜0.05)。 结论 脑瘫伴生长发育迟缓儿童血清IGF-1水平低下，同时肠道菌群群落多样、菌种差异。选择适合的肠道菌群作为脑瘫伴生长发育迟缓的潜在预测标志物，可为开展干预治疗提供新策略。 Abstract:Objective To explore expression of serum insulin-like growth factor-1 (IGF-1) and characteristics of gut microbiota in children with cerebral palsy accompanied by growth retardation, and the association between IGF-1 expression and gut microbiota characteristics, so as to provide the basis for promoting the overall health of children with cerebral palsy accompanied by growth retardation. Methods From June 2022 to June 2023, 112 children with cerebral palsy aged 3-14 years old were randomly selected from a welfare institution in Guangzhou. According to the WHO standard for growth and development delay, 112 children with cerebral palsy were divided into a cerebral palsy accompanied by growth and development delay group (80 cases) and a cerebral palsy accompanied by normal growth and development group (32 cases), and 32 healthy children living in the same institution were selected as the control group. Serum IGF-1 levels were measured in three groups of children, and the gut microbiota was determined using 16S rDNA sequencing technology. The expression characteristics, gut microbiota composition, differential features and correlation of IGF-1 in three groups of children were explored. Results The expression levels of serum IGF-1 in three groups of children were compared, and children with cerebral palsy accompanied by growth retardation[97.70(66.35, 139.50)ng/mL] and cerebral palsy accompanied by normal growth development[149.00(68.30, 233.00)ng/mL] were all lower than those in the healthy control group[169.90(118.75, 293.80)ng/mL], with statistical significance(H=20.13, P < 0.05). The Alpha diversity of gut microbiota in the cerebral palsy with growth retardation group and the cerebral palsy with normal growth group were higher than that in the healthy control group[Chao index(482.50, 489.90, 396.10), Shannon index(6.29, 6.44, 5.89), Simpson index(0.97, 0.97, 0.96)](H=17.20, 7.01, 6.41, P < 0.05). IGF-1 was positively correlated with the relative abundunce of Eubacterium coprostanogenes group and Subdoligranulum (r=0.38, 0.33, P < 0.05). Conclusions Cerebral palsy children with growth retardation show lower level in serum IGF-1, substantial variation in gastrointestinal tract community structure. The appropriate gut microbiota could be used as potential predictive markers of cerebral palsy associated with growth retardation, to provide new strategies for future intervention and treatment. -
Key words:
- Cerebral palsy /
- Developmental disabilities /
- Insulin-like growth factor I /
- Gastrointestinal tract /
- Bacteria /
- Child
1) 利益冲突声明 所有作者声明无利益冲突。2) 黄敏与余小塘为共同第一作者 -
图 1 3组儿童肠道菌群的主成分分析
注：横、纵坐标标识两个选定的主坐标成分，百分比表示主坐标成分对样本组成差异的贡献值，两样本点越接近表明物种组成越相似。
Figure 1. Principal co-ordinate analysis of gut microbiota among three groups of children
图 2 3组儿童肠道菌群的非度量多维尺度分析
注：横、纵坐标标识两个选定的主坐标成分，百分比表示主坐标成分对样本组成差异的贡献值，两样本点越接近表明物种组成越相似。
Figure 2. Nonmetric multidimensional scaling of gut microbiota among three groups of children
表 1 3组儿童身体形态及血清IGF-1水平比较[M(P25，P75)]
Table 1. Comparison of body morphology and IGF-1 levels among the three children groups[M(P25, P75)]
组别 人数 身高/cm BMI/(kg·m-2) HAZ IGF-1/(ng·mL-1) 脑瘫伴生长发育迟缓组 80 112.00(105.00，127.50)ab 13.95(12.08，15.88)b -3.25(-3.82，-2.61)ab 97.70(66.35，139.50)ab 脑瘫伴生长发育正常组 32 125.00(115.00，143.00) 13.30(11.00，15.60)b -1.30(-1.77，-0.58) 149.00(68.30，233.00)b 健康对照组 32 137.50(105.75，147.00) 16.35(14.50，18.15) -0.47(-1.08，0.23) 169.90(118.75，293.80) H值 22.17 20.91 107.65 20.13 P值 ＜0.01 ＜0.01 ＜0.01 ＜0.01 注：a与脑瘫伴生长发育正常组比较，P＜0.05；b与健康对照组比较，P＜0.05。 
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表 2 3组儿童肠道菌群的线性判别分析
Table 2. LEfSe analysis of gut murobita among three groups
组别 微生物类群 LDA分值 脑瘫伴生长发育迟缓组 双岐菌属 4.30 (n=80) 栖粪杆菌属 4.13 Eubacterium coprostanoligenes group 3.89 Christensenellaceae R7 group 3.64 另支菌属 3.37 脑瘫伴生长发育正常组 Clostridia vadinBB60 group 4.05 (n=32) UCG 002 4.03 弯曲菌属 3.99 副拟杆菌属 3.98 Rikenellaceae RC9 gut group 3.92 健康对照组 Escherichia Shigella 4.42 (n=32) 戴阿利斯特杆菌属 3.99 扭链胃球菌属 3.89 罕见小球菌属 3.88 罗姆布茨菌属 3.87
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表 3 3组儿童肠道差异菌群水平与体格发育指标、IGF-1的相关性分析(r值，n=144)
Table 3. 3 Correlation analysis among physical development index, IGF-1 and differential gut murobita levels in children with three groups(r, n=144)
微生物类群 IGF-1 HAZ 体重 BMI 身高 双岐菌属 -0.14 -0.31 -0.37 -0.21 -0.33** 栖粪杆菌属 0.07 0.10 0.19 -0.15 0.35** Eubacterium coprostanoligenes group 0.38** 0.21 0.30** -0.02 0.37** Christensenellaceae R7 group 0.07 0.05 0.11 -0.17 0.24* 另支菌属 0.08 -0.07 0.02 -0.07 0.05 Clostridia vadinBB60 group 0.09 0.00 0.23* 0.16 0.14 UCG 002 -0.08 0.06 0.12 -0.02 0.14 弯曲菌属 0.09 -0.11 -0.07 -0.04 -0.08 副拟杆菌属 0.15 0.23** 0.13 -0.33** 0.38** Rikenellaceae RC9 gut group -0.13 0.04 0.21 -0.02 0.25* Escherichia Shigella -0.05 0.08 -0.07 0.01 -0.10 戴阿利斯特杆菌属 -0.06 0.04 -0.08 0.02 -0.11 扭链胃球菌属 -0.14 0.16 0.02 -0.24* 0.26** 罕见小球菌属 0.33** 0.30** 0.34** 0.17 0.29** 罗姆布茨菌属 -0.06 -0.01 -0.09 -0.22* 0.07 IGF-1 1.00 0.45** 0.58** 0.11 0.55** 注： * P＜0.05，** P＜0.01。
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