Altered circulating blood microbiota in unexplained recurrent spontaneous abortion

Abstract

The etiology of unexplained recurrent spontaneous abortion (URSA) remains poorly understood. Emerging evidence implies that URSA is closely related to dysbiosis of the symbiotic microbiota, while the characteristics of blood microbiome in URSA remain unclear. In the present preliminary exploratory study, 20 patients with URSA and 11 healthy postpartum controls were enrolled for blood microbiome analysis by full-length 16 S rRNA gene sequencing and cytokines profiling by Luminex assay. It was found that although alpha diversity was similar between the two groups, beta diversity analysis revealed a significantly distinct overall microbiota structure in URSA patients. It was found that Blautia wexlerae was remarkably enriched in URSA, while Hydrogenophaga sp. HaHa333 and Zoogloea resiniphila were significantly depleted. Co-occurrence network analysis by topological properties suggested a more pronounced compartmentalized structure with stronger intra‑module associations within the blood microbiome of URSA as indicated by the higher modularity index, which exhibited a predominantly positive and monotonous correlation pattern. Concurrently, the decreased IL-1β and IL-8 in serum co-existed with enrichment of B. wexlerae in URSA. However, IL-27 and IL-13 was elevated, and the level of IL-27 was negatively associated with the URSA-depleted H. sp. HaHa333. In this proof-of-concept investigation, it is the first time to systematically characterize the blood microbiome in URSA patients with cross-sectional clinical observation. These hypothesis-generating findings suggested that URSA is associated with a distinct blood microbiota and an altered cytokine profile, which requires future large-scale validation.