Prevotella as the hub of the cervicovaginal microbiota affects the occurrence of persistent human papillomavirus infection and cervical lesions in women of childbearing age via host NF‐κB/C‐myc

Abstract

There is evidence that coinfection of cervicovaginal high-risk human papillomavirus (HR-HPV) and bacteria is common in women of childbearing age. However, the relationship between bacterial vaginosis (BV) and persistent HR-HPV infection in women of childbearing age and the underlying mechanisms remain unclear. In this study, we determined whether BV affects persistent HR-HPV infection in women aged 20-45 years and explored the possible mechanisms of their interactions. From January 1 to April 30, 2020, we recruited women aged 20-45 years with and without BV at a ratio of 1:2 from Fujian Maternity and Child Health Hospital. All women were followed up at 0, 12, and 24 months. A BV assay, HR-HPV genotyping and cervical cytology were performed at each follow-up. At 0 months, additional vaginal secretions and cervical exfoliated cells were collected for 16S ribosomal RNA sequencing, bacterial metabolite determination, and POU5F1B, C-myc, TLR4, NF-κB, and hTERT quantification. A total of 920 women were included. The

Interactions between microbiota and cervical epithelial, immune, and mucus barrier

“…NOD1 and NOD2 can recognize intracellular PAMPs that can enter the cell through phagocytosis or membrane pores (Anton et al, 2022). BV and associated pathogens, such as Prevotella and Gardnerella, have been shown that associated with the expressions of TLRs and NLRs, especially TLR2/4 (Anahtar et al, 2015;Anton et al, 2022;Dong et al, 2022;Gerson et al, 2022). BV-associated bacteria can induce immune response of cervical cells through the TLR2/4−activated signalling pathways (Zariffard et al, 2005;Anton et al, 2022).…”

“…addition to tryptophan depletion, a recent study found that IFN-g also can down regulate c-Myc, the key regulator of host cell metabolism, resulting in the reduction of TCA cycle intermediates and nucleotides to prevent chlamydial replication and promoting persistence (Rajeeve et al, 2020;Vollmuth et al, 2022). Constitutive expression of c-Myc can rescue CT from persistence induced by IFN-g. Dong et al (Dong et al, 2022) proved that the abundance of Prevotella correlates with the expression of cervical TLR4, NF-kB, C-myc, and hTERT genes. In contrast, Lactobacillus abundance showed negative correlations with these genes.…”

Cervical Microbiome in Women Infected with HPV16 and High-Risk HPVs

“…Overgrowth of Prevotella sp. in the vagina has been linked to the development of cervical lesions caused by persistent Hr-HPV infection by influencing host NF-κB and C-myc signaling pathways [ 45 ]. In addition, Atopobium sp.…”

The role of the genital microbiota in the acquisition and pathogenesis of sexually transmitted infections

“…The cervicovaginal microbiota may alter STI symptomatology, particularly the presence of vaginal discharge and discomfort, or in the case of HPV, viral persistence or development of preneoplastic lesions within the genital tract [91 ▪▪ ] (reviewed in [92]). These symptoms may bias towards STI test seeking behavior, at least for certain STI pathogens, since symptoms of localized inflammation in the genital tract are typical of both cervicovaginal dysbiosis (e.g., BV) and pathogens like N. gonorrhoeae , C. trachomatis , M. genitalium , and Trichomonas vaginalis .…”

“…Vaginal microbiotas dominated by L. crispatus and/or L. gasseri have been associated with a decreased risk of HPV CIN3 progression [78,80] and persistence [79,81]. Prevotella has been implicated in persistence of high-risk HPV types and associated with higher expression of oncogenic and inflammatory markers [91 ▪▪ ].…”