) [52]. Other suspected causative factors for BV include smoking, vaginal lubricants, and the presence of bacteriophages that destroy Lactobacillus spp. [76] and [77]. Evaluations of the longitudinal dynamics of bacterial communities has revealed that some communities change markedly over short time periods, whereas others are relatively stable [54] and [78] (Fig. 4 and Fig. 5). The menstrual cycle is associated with a significant (negative) effect on the stability of the microbiota, but these effects are influenced by bacterial communities [54]. Sexual

activity is also associated with lack of stability. Profiles of CSTs can be derived from time series DNA Synthesis inhibitor of community samples and clustered into five cohorts, which Gajer et al. referred to as community classes [54]. These classes reflect similarities in changes in community composition over time. Some classes were highly dynamic and reflected frequent switches between different CSTs. Classes dominated by L. crispatus and L. gasseri

Fulvestrant chemical structure experienced the fewest fluctuations at the level of community composition, however, some communities that lacked significant number of Lactobacillus spp. also demonstrated stability ( Fig. 5). These communities were stable over time and were observed to have consistently high or intermediate Nugent scores. Vaginal communities dominated by L. iners demonstrated either a lack of constancy or notable stability. L. iners-dominated communities were often seen transitioning to CST Adenylyl cyclase IV, a low-Lactobacillus state. These findings are critical, as they highlight a novel concept – there may be intervals of susceptibility to STIs and risk could be established by the frequency and duration of these increased susceptibility events. The microbiome is thought to impact the Libraries cervicovaginal mucosal immune responses. Certain bacterial products,

particularly from anaerobes, have been shown to result in induction of proinflammatory cytokine production through TLR stimulation [79], dendritic cell activation and maturation [80], and immune cell migration, apoptosis, and phagocytosis through the production of specific short-chain fatty acids [81]. G. vaginalis, a facultative anaerobe, has been shown to produce sialidases, which are capable of inactivating local IgA [82]. The vaginal microbiome plays a major role in women’s reproductive health. We are just beginning to understand the temporal dynamics of vaginal bacterial communities, how they shift from a healthy state to a BV-like state, and how the bacterial communities differ in terms of resistance and resilience to internally or externally imposed disturbances. Surprisingly little is known about the composition of vaginal bacteria across the lifespan, how the interactions of the microbiota with vaccines may vary by age, how they differ between individuals, or how we can harness the vaginal microbiome to protect against STIs.