Lactobacillus spp. create a protective micro-ecological environment through regulating the core fucosylation of vaginal epithelial cells against cervical cancer

Abstract

Vaginal dysbiosis often occurs in patients with cervical cancer. The fucosylation of mucosal epithelial cells is closely related to microbial colonization, and play an important role in protecting the vaginal mucosal epithelial cells. However, no reports on the relationship between vaginal dysbiosis and abnormal mucosal epithelial cell fucosylation, and their roles in the occurrence and development of cervical cancer are unavailable. Here we report that core fucosylation levels were significantly lower in the serum, exfoliated cervical cells and tumor tissue of cervical cancer patients. Core fucosyltransferase gene (Fut8) knockout promoted the proliferation and migration of cervical cancer cells. In patients with cervical cancer, the vaginal dysbiosis, and the abundance of Lactobacillus, especially L. iners, was significantly reduced. Meanwhile, the abundance of L.iners was positively correlated with core fucosylation levels. The L. iners metabolite lactate can activate the Wnt pathway through the lactate-Gpr81 complex, which increases the level of core fucosylation in epidermal cells, inhibiting the proliferation and migration of cervical cancer cells, and have application prospects in regulating the vaginal microecology and preventing cervical cancer.

Disturbances of Vaginal Microbiome Composition in Human Papillomavirus Infection and Cervical Carcinogenesis: A Qualitative Systematic Review

“…Furthermore, L. iners , a strain that is the most common vaginal bacterium in healthy women ( 56 ), was found to be lower in HPV infection, HPV persistence, and Ca, but higher in HSIL. For example, decreased L. iners numbers have been linked to HPV infection, HPV persistence, and Ca ( 19 , 27 , 28 ). Alternatively, the presence of pre-cancer and cancer in women is associated with a high relative abundance of L. iners ( 20 ).…”

“…This intraspecific diversity may be a crucial determinant of structural stability by buffering the dominant Lactobacillus configuration against disturbances ( 58 ). A recent study indicated that the L. iners metabolite, lactate, could inhibit the proliferation and migration of cervical cancer cells ( 19 ). With respect to co-occurrence patterns, suppressed Lactobacillus species L. iners was positively associated with Gardnerella ( 59 ).…”

“…Regarding specific taxa, the most common anaerobes were reported to be associated with HPV infection and cervical dysplasia (i.e., G. vaginals, Megasphaera, Prevotella, and Sneathia) (14), whereas Sneathia and Atopobium were found to be inconsistently abundant (15,16). Other members (i.e., Streptococcus, Staphylococcus, Corynebacterium, Clostridium) have also been reported to be associated with cervical lesions and Ca (17)(18)(19). Additionally, the presence of cervical lesions and Ca among women has been correlated with an increase in Lactobacillus iners (13,20) and a decrease in Lactobacillus jensenii and Lactobacillus crispatus (20).…”

Cancer-associated Lactobacillus iners are genetically distinct and associated with chemoradiation resistance in cervical cancer

“…In the complicated microenvironment of cancer cells, however, these metabolites can also inhibit or accelerate the proliferation of malignant tumors (Zadravec, Štrukelj and Berlec, 2015; Homburg et al ., 2017). In fact, one previous study showed that ATCC L. iners (used as our non-cancer control) actually inhibited the proliferation and migration of cervical cancer cells by activating the WNT pathway in epidermal cells (Fan et al ., 2021). In HPV-related cervical cancer, the presence of Lactobacillus spp has been shown to widely vary with a typically reduced prevalence of L. crispatus and an L .…”

Influence of Lacidophilin Vaginal Capsules plus rh-IFN-α2b on Efficacy, Vaginal Microecology, and Safety of Patients with HPV Infection

“…As a carcinogenic factor, HPV infection can also cause cancers in the vulva, anus, and oropharynx [ 3 ]. The carcinogenic mechanism of HPV infection is shown to be related to vaginal microecology, inflammatory factors, genetics, and immune function [ 4 , 5 ]. This study analyses the clinical effect of drug therapy on HPV infection, aiming to provide novel references for the improvement of vaginal microecology and alleviation of inflammatory factors in HPV-infected patients.…”