Table 1_Characterization of gut microbiota signatures in Indian preterm infants with necrotizing enterocolitis: a shotgun metagenomic approach.docx

IntroductionNecrotizing enterocolitis (NEC) is an inflammatory bowel disease that primarily affects preterm infants. Predisposing risk factors for NEC include prematurity, formula feeding, anemia, and sepsis. To date, no studies have investigated the gut microbiota of preterm infants with NEC in India.
MethodIn the current study, shotgun metagenomic sequencing was performed on fecal samples from premature infants with NEC and healthy preterm infants (n = 24). Sequencing was conducted using the NovaSeq X Plus platform, generating 2 × 150 bp paired-end reads. The infants were matched based on gestational age and postnatal age.
ResultThe median time to NEC diagnosis was 9 days (range: 1–30 days). Taxonomic analysis revealed a high prevalence of Enterobacteriaceae at the family level, with the genera Klebsiella and Escherichia particularly prominent in neonates with NEC. No statistically significant differences in alpha or beta diversity were observed between stool samples from infants with and without NEC. Linear regression analysis demonstrated that Enterobacteriaceae were significantly more abundant in stool samples from infants with NEC than without NEC (q < 0.05). Differential abundance analysis using Linear Discriminant Analysis Effect Size (LEfSe) identified Klebsiella pneumoniae and Escherichia coli as enriched in the gut microbiota of preterm infants with NEC. Functional analysis revealed an increase in genes associated with lipopolysaccharide (LPS) O-antigen, the type IV secretion system (T4SS), the L-rhamnose pathway, quorum sensing, and iron transporters, including ABC transporters, in stool samples from infants with NEC.
ConclusionThe high prevalence of Enterobacteriaceae and enrichment of LPS O-antigen and T4SS genes may be associated with NEC in Indian preterm infants.

引言
坏死性小肠结肠炎（Necrotizing enterocolitis, NEC）是一种主要累及早产儿的炎症性肠病。该病的易感危险因素包括早产、配方奶喂养、贫血及败血症。截至目前，尚未有针对印度坏死性小肠结肠炎早产儿肠道菌群的相关研究。

方法
本研究对24名坏死性小肠结肠炎早产儿与健康早产儿的粪便样本开展鸟枪宏基因组测序。测序采用NovaSeq X Plus平台，生成2×150 bp双端读长序列。两组婴儿按胎龄及生后年龄进行匹配。

结果
本研究中，坏死性小肠结肠炎确诊的中位时间为9天（范围：1~30天）。分类学分析显示，在科水平上肠杆菌科（Enterobacteriaceae）的检出率极高，其中克雷伯菌属（Klebsiella）与埃希菌属（Escherichia）在坏死性小肠结肠炎新生儿的粪便菌群中尤为突出。两组婴儿粪便样本的α多样性与β多样性均未呈现统计学显著性差异。线性回归分析表明，坏死性小肠结肠炎患儿粪便样本中的肠杆菌科丰度显著高于健康早产儿（q<0.05）。采用线性判别分析效应尺寸（Linear Discriminant Analysis Effect Size, LEfSe）进行差异丰度分析，结果显示肺炎克雷伯菌（Klebsiella pneumoniae）与大肠埃希菌（Escherichia coli）在坏死性小肠结肠炎早产儿的肠道菌群中显著富集。功能分析显示，坏死性小肠结肠炎患儿的粪便样本中，与脂多糖（Lipopolysaccharide, LPS）O抗原、Ⅳ型分泌系统（Type IV Secretion System, T4SS）、L-鼠李糖代谢途径、群体感应以及包括ABC转运蛋白在内的铁转运蛋白相关的基因丰度均有所升高。

结论
本研究结果提示，肠杆菌科的高检出率以及脂多糖O抗原、Ⅳ型分泌系统相关基因的富集，可能与印度早产儿坏死性小肠结肠炎的发生相关。