Table 1.

Known disruptions to the urogenital microbiome. Abbreviations: spp.—species; IL—interleukin; IUD—intrauterine device; LNG—levonorgestrel; CST—community state type; GI—gastrointestinal; HPV—human papilloma virus.

Disruption	Mechanism	Result	Reference
Biological
Menstruation	Temporary dip in estrogen during the secretory phase	Estrogen promotes proliferation of Lactobacillus spp. Responsible for maintaining a low vaginal pH. A decrease in estrogen levels results in a decrease in Lactobacilli and a temporary rise in vaginal pH which increases susceptibility to opportunistic pathogens.	Bardos et al., 2020 [36]
Menopause	Decrease in overall estrogen levels	Chronic low estrogen levels decrease accumulation of glycogen in the vaginal epithelium thereby reducing colonization of lactobacilli dependent on epithelial glycogen levels.	Achilles et al., 2018 [37]
Pregnancy	Inflammatory responses are moderated	Towards the end of pregnancy, the lower reproductive tissues increase microbial diversity and decrease Lactobaccilus spp.	Bardos et al., 2020 [36]
Lifestyle
Hygiene products	Changes to pH levels	Vaginal douching has been linked to increased susceptibility to bacterial vaginosis.	Brotman et al., 2008 [38]
Tampons	Changes to lactic acid production and pH	Decreased vaginal microbiome stability is associated with tampon use.	Carter et al., 2018 [39]
Antibiotic use	Killing of commensal bacteria	Depletion of commensal bacteria due to antibiotic treatment was found to cause increased secretions of IL-33 in vaginal epithelium, suppressing antiviral immunity.	Oh et al., 2016 [40]
IUD-use	Changes in commensal microbial populations	Copper IUD use was associated with an increase in Gardnerella vaginalis and Atopobium vaginae possibly leading to increased bacterial vaginosis risk. LNG-releasing IUD use was associated with a decrease in Lactobacillus spp. Furthermore, an increase in Candida spp.	Achilles et al., 2018 [37]
Sexual activity	Changes in commensal microbial populations, shift in CST type	The number of sex partners and age when sexual activity started is associated with CST grouping and microbiome stability. Women with new sexual partners are at an increased risk for bacterial vaginosis.	Chen et al., 2017 [8]
Causative Pathogenesis
Leaky gut	Hematogenous spread of GI commensals into peritoneal cavity	Increased risk of placental infection, pre-term birth, and miscarriage	Bardos et al., 2020 [36]
Periodontal disease	Microbial transmission from oral cavity	Increased risk of intra-uterine infection and pre-eclampsia	Parihar et al., 2015 [41]
Resultant Pathogenesis
HPV infection	Opportunistic infection	Subjects with HPV infections have less Lactobacillus spp. Furthermore, more microbial diversity	Nicolò et al., 2021 [42]
Cervical cancer	Variable gene expression of L. iners-dependent community functionality and composition	L. Iners decreased amongst women with HPV infection, suggesting a protective effect. Alternatively, L. iners is associated with CIN 2+ and ICC	Piyathilake et al., 2016 [43]