Figure 2.

Endometrial microbiota interplay in the uterus. Uterine microbes could impact the genomic stability of uterine epithelia through modulation of transcription factors and other genomic and epigenetic alterations; also, microbial-secreted metabolites may support the growth of specific species and suppress the growth of other bacteria; and the consumption of a limited resource can starve the pathogenic invaders. In short, the endometrium is an immunologically suited niche for microbes: the endometrial immune system needs to be well adapted to withstand the continuous threat caused by microbial colonisation of the large endometrial mucosal surface, separated from host tissue by only a single layer of epithelial cells. Thus, tissue invasion of microbes must be limited in order to prevent potentially harmful inflammation or imbalance in the symbiotic relationship. Endometrial microbial homeostasis is probably regulated in three different ways: (1) a single layer of columnar epithelial cells forming a strong barrier through tight junctions anatomically limiting exposure of resident bacteria to the systemic immune system; (2) immune mediators such as infection-controlling molecules (antimicrobial peptides, AMPs) that are present in the endometrial mucosal surface and the endometrial fluid [99] and could restrict direct contact between epithelia and microbes; and (3) a rapid detection (epithelial cells express pattern recognition receptors (PRRs) that recognise and act to pathogens) and killing of bacteria upon a barrier breach by the endometrial lymphocytes that are present throughout all stages of the menstrual cycle [100,101].