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多组学整合通过16S rRNA测序和代谢组学确定早产儿视网膜病变的关键生物标志物。

Multi-omics integration identifies key biomarkers in retinopathy of prematurity through 16S rRNA sequencing and metabolomics.

作者信息

Guo Linlin, Wang Ruoming, Han Liping, Fu Yongcheng, Wang Xiujuan, Nie Lintao, Fu Wenjun, Ren Hongyan, Wu Lijia, Li Guangshuai, Ding Juan

机构信息

The Second Department of Radiotherapy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Nursing, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Front Microbiol. 2025 Jun 18;16:1601292. doi: 10.3389/fmicb.2025.1601292. eCollection 2025.

Abstract

BACKGROUND

The gut microbiome is increasingly recognized for its role in the pathogenesis of neonatal conditions commonly associated with retinopathy of prematurity (ROP). This study aimed to identify key intestinal microbiota and metabolites in ROP and examine their relationships.

METHODS

Fecal samples were collected from infants with and without ROP at weeks 2 (T1) and 4 (T2) for 16S rRNA sequencing. At T2, additional fecal samples underwent non-targeted metabolomic analyses. A combined analysis of the 16S rRNA sequencing and metabolomics data was performed.

RESULTS

No significant differences in α-diversity indexes were observed between the ROP and non-ROP at T1. However, at T2, the Chao, ACE, and Shannon indices were significantly higher, whereas the Simpson index was lower in ROP compared to non-ROP. At the phylum level, the dominant phyla at T2 included , , , , and . LEfSe analysis of T2 showed that , , , , , , and as key genera associated with ROP. Metabolomic analysis identified 382 differentially accumulated metabolites, which were enriched in steroid hormone biosynthesis; the PPAR signaling pathway; linoleic acid metabolism; histidine metabolism; and alanine, aspartate, and glutamate metabolism. Additionally, the AUC of the combined analysis exceeded that of differential bacterial communities (0.9958) alone.

CONCLUSION

This study revealed characteristic changes in the intestinal flora and metabolites in ROP, which provide promising targets/pathways for ROP diagnosis and therapy.

摘要

背景

肠道微生物群在与早产儿视网膜病变(ROP)相关的新生儿疾病发病机制中的作用日益受到认可。本研究旨在确定ROP中的关键肠道微生物群和代谢产物,并研究它们之间的关系。

方法

在第2周(T1)和第4周(T2)从患有和未患有ROP的婴儿中收集粪便样本进行16S rRNA测序。在T2时,对额外的粪便样本进行非靶向代谢组学分析。对16S rRNA测序和代谢组学数据进行联合分析。

结果

在T1时,ROP组和非ROP组之间的α多样性指数没有显著差异。然而,在T2时,与非ROP组相比,ROP组的Chao、ACE和Shannon指数显著更高,而Simpson指数更低。在门水平上,T2时的优势门包括 、 、 、 和 。T2的LEfSe分析表明, 、 、 、 、 、 和 是与ROP相关的关键属。代谢组学分析确定了382种差异积累的代谢产物,这些产物在类固醇激素生物合成、PPAR信号通路、亚油酸代谢、组氨酸代谢以及丙氨酸、天冬氨酸和谷氨酸代谢中富集。此外,联合分析的曲线下面积超过了单独的差异细菌群落分析(0.9958)。

结论

本研究揭示了ROP中肠道菌群和代谢产物的特征性变化,为ROP的诊断和治疗提供了有前景的靶点/途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6af5/12213487/cce06e95f9bd/fmicb-16-1601292-g006.jpg

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