Distinct vaginal microbial signatures in pregnancies complicated by antiphospholipid syndrome: depletion of Lactobacillus johnsonii and enrichment of Bifidobacterium dentium

ABSTRACT Antiphospholipid syndrome (APS) is a systemic autoimmune disease that contributes substantially to recurrent pregnancy loss, fetal death, intrauterine growth restriction, and preeclampsia, posing major threats to maternal and fetal health. These obstetric complications exhibit clinical similarities to those resulting from vaginal dysbiosis, yet the vaginal microbiota in APS pregnancies has not been systematically investigated. In this study, we characterized the vaginal microbiome in 33 pregnant women with APS and 90 healthy controls using 16S rRNA gene sequencing. We identified a unique microbial signature in APS pregnancies that differed from the commonly observed pattern of increased microbial diversity and Lactobacillus depletion seen in classical vaginal dysbiosis. Specifically, while overall alpha diversity and Lactobacillus dominance were preserved, we observed distinct compositional restructuring characterized by selective depletion of Lactobacillus johnsonii and marked enrichment of Bifidobacterium dentium . A logistic regression model integrating the relative abundances of these microbial biomarkers demonstrated robust diagnostic performance in differentiating pregnancies with APS from healthy pregnancies, with risk scores significantly correlating with clinical parameters and pregnancy outcomes. This study demonstrates that pregnant women with APS display a distinct vaginal microbiome pattern defined by species-specific compositional restructuring rather than global dysbiosis. These microbial alterations may contribute to APS-related pregnancy morbidity, highlighting vaginal microbial signatures as promising noninvasive biomarkers for risk stratification and potential therapeutic targets in obstetric APS management. IMPORTANCE Antiphospholipid syndrome (APS) is an autoimmune disease that causes recurrent miscarriage, fetal death, and pregnancy complications in women of reproductive age. While coagulation dysfunction is a known contributing factor, whether APS is accompanied by vaginal microbiota alterations and their role in adverse outcomes remains unclear. We discovered that pregnant women with antiphospholipid syndrome harbor a unique vaginal microbial community: they exhibit depletion of the protective species Lactobacillus johnsonii while showing enrichment of Bifidobacterium dentium , a bacterium typically found in the gut. Unlike typical vaginal infections that display widespread microbial dysbiosis, antiphospholipid syndrome induces only selective alterations in specific bacterial species. These microbial signatures correlated with hematological parameters and adverse pregnancy histories, including prior miscarriages. Our findings suggest that monitoring vaginal microbiota could provide a simple, noninvasive approach to identify high-risk pregnancies in women with antiphospholipid syndrome and may guide novel screening strategies for pregnancy-related disorders targeting the vaginal microbiome.