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. 2025 Feb 8;25(1):130.
doi: 10.1186/s12884-025-07218-7.

Amniotic fluid microbiota and metabolism with non-syndromic congenital heart defects: a multi-omics analysis

Wenli Xu #  1   2 , Lu Li #  1 , Hong Kang  1 , Meixian Wang  1 , Yanqun Liu  3 , Guicun Wang  4 , Ping Yu  1   2 , Juan Liang  1   2 , Zhen Liu  5   6
Affiliations

Amniotic fluid microbiota and metabolism with non-syndromic congenital heart defects: a multi-omics analysis

Wenli Xu et al. BMC Pregnancy Childbirth. .

Abstract

Background and aims: Recent studies have indicated possible links between the microbiota and the fetal heart, while the relevant mechanism is still unknown. This study is aims to investigate whether analyzing the microbiota and metabolic profiles of amniotic fluid collected from pregnant women whose fetuses with or without non-syndromic congenital heart defects (CHDs), during the second and third trimester of pregnancy, could offer valuable insights into CHDs.

Methods and results: A case-control study was conducted with 17 cases diagnosed with non-syndromic CHDs (CHDs group) and 34 controls without congenital anomalies (control group) at a ratio of 1:2. The 16 S rDNA gene sequencing and metabolomics methods were employed to assess 51 amniotic fluid samples. The amniotic fluid microbiome from the CHDs group exhibited significantly higher Shannon and Simpson indices compared to the control group. At the genus level, 240 bacterial taxa were substantially enriched in the two groups, with 93 of those taxa being highly enriched in the case group. Compared to the control group, the case group exhibited 177 metabolites that were significantly increased and 480 metabolites that were down-regulated. The differential metabolites were primarily enriched in the steroid hormone biosynthesis, bile secretion and ovarian steroidogenesis, according to KEGG analysis. The observed variations in nine metabolites could attributed to fifty-eight distinct bacterial taxa. The nine differential metabolites were mainly associated with pathways involving steroid hormone biosynthesis, bile secretion, glycolysis, tricarboxylic acid (TCA) cycle, NADPH metabolism, and acyl transfer pathways.

Conclusion: The CHDs group has disturbed amniotic fluid microbiota and metabolites, and more research was required to elucidate the mechanism.

Keywords: Birth development; Congenital heart defects; Metabolite; Microbiota; Multiomics analysis.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The program was approved by the Ethics Committee of Sichuan University (No. 2010004) and West China Second University Hospital (No. 2015(011)). All subjects provided informed consent during the enrollment process. Consent for publication: The work has not been published elsewhere and does not contain any content that infringes upon the rights of others, including copyright or privacy rights. The author understand that once published, the work will be publicly accessible. Clinical trial number: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The amniotic fluid alpha-diversity and beta-diversity of the case and control groups, estimated by the Shannon index (a), Simpson index (b), and ACE index (c), and the different amniotic fluid microbiota composition between the case and control groups by PCoA based on Bray_Curtis distance (d)
Fig. 2
Fig. 2
The amniotic fluid microbiota composition of the case and control groups, at the genus level (a) and differentially abundant microbial taxa identified by LEfSe analysis (LDA score > 4 and P < 0.05; b)
Fig. 3
Fig. 3
Variations of amniotic fluid metabolites between the case and control groups. (a) OPLS-DA analysis under the comprehensive positive and negative ion mode. (b) The leading differential metabolic pathways according to the KEGG analysis of differential metabolites
Fig. 4
Fig. 4
The heatmap describing the information on contributing reactions for each taxon-metabolite pair. Contribution results were only included for metabolites with a model p-value less than 0.1
See this image and copyright information in PMC

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