The success of implantation and pregnancy development is based on interactive processes and complex signaling between embryonic and maternal tissues. Modulation of the maternal immune system prior to conception thus plays a major role in determining subsequent pregnancy outcome. During early pregnancy, even subtle alterations in endometrial immunity and in the surrounding environment can have potentially negative impacts on the implantation process and placental development. Consistent with this, several studies have shown that an abnormal endometrial inflammatory status is associated with recurrent pregnancy loss. Furthermore, reduced immune tolerance to trophoblastic tissues has been suggested as an early mechanism responsible for “poor placentation” and pre-eclampsia, the obstetric syndrome characterized by the occurrence of arterial hypertension and proteinuria, which is still a main cause of maternal and neonatal morbidity and mortality.

Growing evidence suggests that both local and systemic immunity are greatly influenced by the microbiota. Interestingly, recent work suggests that the uterus is likely a non-sterile compartment. Lessons learned from the gut microbiome indicate that the uterine microbiome may be able to modulate immune cell subsets needed for implantation, thereby having potential implications for placental development and pregnancy outcome. The uterine microbiota can also be crucial in protection against uterine infections by defending their niche and competing with pathogens. This may have huge implications for reducing the risk of chorioamniotitis, responsible for 40-70% preterm births due to premature membrane rupture and/or spontaneous labor. However, the impact of maternal bacterial colonization on pregnancy outcomes depends not only on the composition of the microbiome, but also on genetic factors and environmental stimuli, that are able to influence maternal immune responses.

In conclusion, a normal, healthy endometrial state, including the local immune environment, is crucial not only for fertility but also for placenta formation, since the initiation of placentation highly depends on interaction between trophoblasts and immune cells such as decidual natural killer cells and T cells. Future research is needed to increase our understanding of how the vagina and the uterus are colonized by microbes; how these microbiomes influence the modulation of the immune system and how this interplay influences implantation, placental development and pregnancy outcome.

This Research Topic aims to summarize recent developments in the field, focusing on:
(a) Current knowledge of normal female genital tract microbiome
(b) Immunity and maternal microbiome
(c) The interplay between immunity, maternal uterine, vaginal and gut microbiome and obstetric syndromes (recurrent pregnancy loss, placental-insufficiency, preterm delivery etc.)
(d) Novel therapeutic approaches towards restoring a normal female genital tract microbiome
(e) How maternal uterine, vaginal and gut microbiome may impact preterm infant microbiome composition and the future wellbeing of newborns

We welcome the submission of the following article types to this Research Topic: Original Research Articles, Reviews and Mini-Reviews.

Topic Editor Eytan R. Barnea is the Founder and Chief Scientific Officer of BioIncept, LLC. All other Topic Editors declare no competing interests with regards to the Research Topic subject.

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Frontiers in Immunology

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