Moderating role of blood inflammatory markers in the vaginal microbiota-fibrinogen relationship in URSA-affected women

The etiology and pathogenic mechanisms underlying recurrent spontaneous abortion (RSA) are poorly understood. Specifically, patients with unexplained recurrent spontaneous abortion (URSA) frequently exhibit dysbiosis of the vaginal microbiota and elevated blood inflammatory markers. Therefore, this study aimed to investigate the association between vaginal microbiota, blood inflammatory markers, and fibrinogen in URSA, with a specific focus on exploring the potential moderating role of inflammatory markers in the relationship between vaginal microbiota and fibrinogen dynamics. Thirty-one pregnant women with URSA and fifty pregnant women with normal pregnancies completed clinical biochemical indicator testing and vaginal secretion testing in early pregnancy. The characteristics of vaginal microbiomes in patients with URSA and healthy women were evaluated via 16 S rRNA gene sequencing of the V3-V4 region using Illumina MiSeq sequencing. Hayes’ regression was used to analyze the association among vaginal microbiota, blood inflammatory markers, and vaginal microbiota*blood inflammatory markers with fibrinogen. Simple slope analysis was applied to visualize the interaction. The URSA group showed decreased alpha diversity. Principal coordinates analysis revealed significant differences in vaginal microbiota between the URSA and control groups (unweighted UniFrac distance, R2 = 0.03, P = 0.007). Erysipelotrichaceae was positively associated with fibrinogen (B = 6.34, P < 0.05), and NLR was positively associated with fibrinogen (B = 1.46, P < 0.05). However, the combined effect of Erysipelotrichaceae and NLR was negatively associated with fibrinogen (B = -1.5, P < 0.05). The association between Erysipelotrichaceae and fibrinogen was significant in the low NLR group (1 standard deviation (SD) below the mean, B = 3.64, standard error (SE) = 1.15, P < 0.01) but not significant in the high NLR group (1 SD above the mean, B = 0.93, SE = 0.644, P > 0.05). Additionally, the association between Erysipelotrichaceae and fibrinogen was significant in the low WBC group (1 SD below the mean, B = 2.84, SE = 0.94, P < 0.01) but not significant in the high WBC group (1 SD above the mean, B = -0.137, SE = 0.89, P > 0.05). Blood inflammatory markers moderate the link between vaginal microbiota and fibrinogen. Further studies are needed to explore the potential biological mechanisms linking vaginal microbiota and coagulation markers for URSA treatment and to validate our findings.