Investigation of the relationship between vaginal dysbiosis with the activation of genital and intestinal inflammation during the pregnancy in an in vivo mouse model

The vaginal microbiota dysbiosis is represented by a low rate of Lactobacillus and several facultative pathogens such as Gardnerella, Atopobium, and Prevotella. A low abundance of Lactobacillus crispatus and a high abundance Gardnerella vaginalis and Atopobium vaginae species are significantly associated with preterm birth. The host-microbiota has been shown to regulate maternal and fetal immune interaction and birth outcomes. Bacterial taxa associated with dysbiosis have been found to stimulate proinflammatory cytokines that induce preterm labor. Progesterone treatment is one of the targeted therapies to prevent premature birth. The study aims to investigate the role of dysbiotic microbiota in the inflammatory process in a mouse model and also the effect of progesterone treatment on immune modulation in the genital and intestinal systems during pregnancy. Our mouse model revealed that vaginal exposure to dysbiotic microbiota showed an increasing trend of proinflammatory cytokine levels in the uterus and pathological inflammation through macrophage accumulation, resulting in 28% preterm birth. After the progesterone treatment in the dysbiosis group, TNFa and IL-6 levels were decreased. Besides, the macrophage density in the uterus was reduced, and less cellular damage in the placenta was observed. Analyzing the vaginal microbiota before or during pregnancy may support the decision for initiation of progesterone therapy. Besides, our results may guide new strategies like personalized treatments with novel drugs for preventing preterm birth.