Table_1_The Impact of Gut Microbiome on Metabolic Disorders During Catch-Up Growth in Small-for-Gestational-Age.docx

ObjectiveCatch-up growth (CUG) in small for gestational age (SGA) leads to increased risk of metabolic syndrome and cardiovascular diseases in adults. It remains unclear if microbiota could play an important role in CUG-SGA independent of genetic or nutritional factors. The present study explored the role of gut microbiota in, and its association with, metabolic disorders during CUG-SGA.
MethodsAn SGA rat model was established by restricting food intake during pregnancy, and the rats were divided into catch-up growth (CUG-SGA) and non-catch-up growth (NCUG-SGA) groups based on body weight and length at the fourth postnatal week. High-throughput sequencing of 16S rRNA was conducted to detect the diversity and composition of the gut microbiota. Fecal short-chain fatty acids (SCFAs) were detected by gas chromatography-mass spectrometry. Transcriptome sequencing of liver tissue was performed and verified using real-time PCR. Concentrations of insulin and total cholesterol were determined using enzyme-linked immunosorbent assay.
ResultsThe composition of gut microbiota in CUG-SGA rats differed from that of NCUG-SGA rats, with reduced abundance of Lactobacillus in the CUG-SGA group. The decrease in Lactobacillus was significantly associated with increased body weight and upregulated insulin and total cholesterol levels. Five SCFAs and two branched chain fatty acids were significantly higher in the CUG-SGA group than in the NCUG-SGA group. Additionally, SCFAs were positively associated with clinical indices such as weight, body mass index, insulin, and total cholesterol. Transcriptomic data revealed that insulin-like growth factor-2 expression was significantly decreased in CUG-SGA rats and was associated with a decrease in Lactobacillus bacteria.
ConclusionLactobacillus and SCFAs were associated with the metabolic disorders during CUG in SGA. Gut microbiome may play a certain role on metabolic disorders during catch-up growth in small-for-gestational-age.

目的 小于胎龄儿（small for gestational age, SGA）发生追赶生长（catch-up growth, CUG）后，成年后罹患代谢综合征与心血管疾病的风险显著升高。目前尚不明确肠道菌群是否可独立于遗传或营养因素，在CUG-SGA进程中发挥关键作用。本研究探讨了肠道菌群在SGA追赶生长过程中的作用，及其与代谢紊乱的关联。
方法 本研究通过限制孕期进食量构建SGA大鼠模型，并于出生后第4周根据体质量与体长将大鼠分为追赶生长组（CUG-SGA组）与非追赶生长组（NCUG-SGA组）。采用16S rRNA高通量测序检测肠道菌群的多样性与组成；通过气相色谱-质谱联用技术检测粪便短链脂肪酸（short-chain fatty acids, SCFAs）水平；对肝脏组织进行转录组测序，并采用实时荧光定量PCR（real-time PCR）进行验证；采用酶联免疫吸附试验测定血清胰岛素与总胆固醇浓度。
结果 CUG-SGA大鼠的肠道菌群组成与NCUG-SGA大鼠存在显著差异，CUG-SGA组乳杆菌属（Lactobacillus）的丰度降低。乳杆菌属丰度降低与体质量升高、胰岛素及总胆固醇水平上调显著相关。CUG-SGA组的5种短链脂肪酸与2种支链脂肪酸水平显著高于NCUG-SGA组；此外，短链脂肪酸与体质量、体质量指数、胰岛素及总胆固醇等临床指标呈正相关。转录组数据显示，CUG-SGA大鼠体内胰岛素样生长因子-2（insulin-like growth factor-2）的表达量显著降低，且该表达变化与乳杆菌属丰度下降存在关联。
结论 乳杆菌属与短链脂肪酸与SGA追赶生长过程中的代谢紊乱相关。肠道菌群可能在小于胎龄儿追赶生长所致的代谢紊乱中发挥一定作用。