Multi-Omics Analysis Reveals Inflammatory Activation and Maternal-Fetal Interface Remodeling in Spontaneous Abortion

Abstract

Background

Spontaneous abortion (SA) is a common adverse outcome of early pregnancy, yet its underlying pathophysiological mechanisms remain incompletely understood. Accumulating evidence suggests that dysregulated inflammatory responses at the maternal-fetal interface play a critical role in pregnancy loss. However, the potential associations between alterations in gut microbiota, metabolic disturbances, and localized decidual inflammation in patients with SA have not been systematically characterized.

Methods

Women with SA (n = 30) and those with normal early pregnancy (NP, n = 28) were enrolled in this study. Proinflammatory cytokines were quantified in decidual tissue homogenates, and histopathological and molecular analyses were performed to evaluate inflammatory activation at the maternal-fetal interface. The gut microbiota composition was profiled using shotgun metagenomic sequencing, while metabolic alterations in the feces were assessed by untargeted metabolomics. Integrated multi-omics analyses were conducted to explore associations among gut microbial dysbiosis, metabolic perturbations, decidual inflammatory signaling, and molecular alterations.

Results

Compared with those from the NP group, the decidual tissues from the SA group exhibited significantly elevated levels of IL-1β and TNF-α (1.49-fold and 1.51-fold, both P < 0.0001), accompanied by pronounced histopathological abnormalities. Enhanced activation of the NF-κB signaling pathway was observed at the maternal–fetal interface in SA patients. Metagenomic analyses revealed distinct differences in the gut microbiota composition and community structure between the two groups, with differentially abundant bacterial taxa identified (LDA score > 2.0). Consistent with these findings, fecal metabolomic profiling clearly revealed differences between SA and NP patients, with differentially abundant metabolites (VIP > 1.0, adjusted P < 0.05) predominantly enriched in lipid metabolism, amino acid metabolism, and immune-related pathways. In addition, the expression of leucine-rich repeat-containing G protein-coupled receptor 6 was significantly upregulated (P < 0.0001) in the decidual tissue of SA patients.

Conclusions

These findings indicate that SA is associated with localized inflammatory activation at the maternal-fetal interface, dysregulation of decidual molecular activity, gut microbiota dysbiosis, and metabolic perturbations. Integrated multi-omics analyses suggest potential interactions among these factors that may be linked to decidual dysfunction during early pregnancy, providing new insights into the complex pathophysiology of SA.

Keywords

Spontaneous abortion / Maternal-fetal interface / Inflammation / Gut microbiota / Metabolomics / Multi-omics / Decidual tissue / Leucine-rich repeat-containing G protein-coupled receptor 6

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