Vaginal Microbial Environment Skews Macrophage Polarization and Contributes to Cervical Cancer Development

Zhou, Guannan; Zhou, Fang; Gu, Yuanyuan; Zhang, Menglei; Zhang, Ganrong; Shen, Fang; Hua, Keqin; Ding, Jing

doi:10.1155/2022/3525735

Cited by 11 publications

(4 citation statements)

References 25 publications

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“…In addition, researchers also revealed that tumors (CRC, cervical cancer, and endometrial cancer) were associated with the high level of Prevotella genus, which disrupt vagina homeostasis and contribute to bacterial vaginosis 36 , 37 . We also found that the abundance of Peptostreptococcus was significantly increased in EOC patients, which is an opportunistic pathogen and has been proven by Zhou et al ., to promote cervical cancer development via inducing macrophage polarization, which secreted VEGF to benefit the angiogenesis 38 . Although we observed the significant growth in these pathogenic bacteria ( Bacteroides, Prevotella , and Peptostreptococcus ) and the reduction in probiotics ( Bifidobacterium ), the specific mechanism of these bacteria in EOC progression awaits further investigation.…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota dysbiosis promotes the development of epithelial ovarian cancer via regulating Hedgehog signaling pathway

et al. 2023

Gut Microbes

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Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer, which remains a threat to female health at all ages. Hypotheses for EOC development include the continuous presence of inflammation, in which microbiota and inflammatory cytokines participate in cancer-related signaling pathway activation. Hedgehog (Hh) signaling is prominent for EOC progression, and interacts with inflammation response related to gut microbiota (GM). However, the precise roles of GM during this process are unknown. Here, we showed that the GM from patients with EOC differed from that of healthy women and had GM dysbiosis. We found that EOC modeling may lead to GM changes in mice, and it restored after the administration of GM from healthy controls, while GM from patients with EOC further exacerbated GM dysbiosis. Furthermore, we found that GM from EOC markedly promoted tumor progression and activated Hh signaling; meanwhile, it increased the extent of inflammation and activated NF-κB signaling, but GM from healthy controls improved them. Our results demonstrate how GM dysbiosis promoted EOC progression by activating Hh signaling mediated by TLR4/NF-κB signaling. We anticipate our assay to be a new thought for exploring the role of GM in EOC development. Furthermore, improving GM dysbiosis is a novel therapeutic approach for delaying EOC development.

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Section: Discussionmentioning

confidence: 99%

Gut microbiota dysbiosis promotes the development of epithelial ovarian cancer via regulating Hedgehog signaling pathway

et al. 2023

Gut Microbes

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“…There were several other genera being great importance in disease prediction, such as Streptomyces , Peptostreptococcus , Bauldia , since their coexistence in both models. Genus Peptostreptococcus might benefit the development of cervical cancer 42 . Additionally, when vaginal homeostasis is disrupted, for example, the replacement of Lactobacillus population by other microbes, favors the growth of Peptostreptococcus anaerobius 43 .…”

Section: Discussionmentioning

confidence: 99%

“…Genus Peptostreptococcus might benefit the development of cervical cancer. 42 Additionally, when vaginal homeostasis is disrupted, for example, the replacement of Lactobacillus population by other microbes, favors the growth of Peptostreptococcus anaerobius. 43 While for Streptomyces and Bauldia, there are few information available with regard to vaginal microbiota.…”

Section: Diagnostic Potential Of Hrcd Based On the Vaginal Microbial ...mentioning

confidence: 99%

HPV‐related cervical diseases: Alteration of vaginal microbiotas and promising potential for diagnosis

Rao

Fan

et al. 2022

Journal of Medical Virology

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Vaginal microbiota is closely associated with women's health, however, the correlation between HPV‐related cervical disease (HRCD) and vaginal microbiota is still obscure. In this study, patients with HRCD (n = 98) and healthy controls (n = 58) in Hangzhou were recruited, and their vaginal microbiota were collected and analyzed. The composition of the vaginal microbial community was explored, and a disease classification model was developed by random forest algorithm. The results suggested that the diversity of vaginal microbiota was significantly higher in HRCDs than that in healthy controls (p < 0.05). Firmicutes is the dominant phylum in vaginal microbiota, and Lactobacillus was identified as the most altered genus between two groups (p < 0.01). Kyoto Encyclopedia of Genes and Genomes analysis suggested the difference in vaginal microbial community functions between two groups. Furthermore, we identified 10 biomarkers as the optimal marker sets for the random forest model and found a higher probability of disease values in HRCD group in discovery cohort (p < 0.0001), with an area under the receiver operating characteristic curve reaching 89.7% (95% confidence interval: 78.3%–100%). We further validated the model in both validation and independent diagnosis cohorts, confirming its accuracy in the prediction of HRCD. In conclusion, this study revealed the community composition of vaginal microbiota in HRCDs and successfully constructed a diagnostic model for HRCD.

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“…Studies have demonstrated the role of the vaginal microbial environment (anaerobic Actinomyces) in cervical cancer [23]. Functional assays, including cell proliferation, tube formation, and immuno uorescence staining, have revealed mechanisms by which anaerobic Actinomyces-induced macrophages secrete VEGF, stimulating cervical cancer angiogenesis in vitro and in vivo.…”

Section: Initial Investigations Have Revealed a Distinctive Compositi...mentioning

confidence: 99%

Exploring the Vaginal Microbiome's Role in HPV Infection Dynamics: A Prospective Cohort Study

Liu,

Wang,

et al. 2024

Preprint

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Background The incidence of cervical cancer is often associated with the persistent infection of Human Papillomavirus (HPV). Identifying biomarkers that can monitor the progression of HPV infection and predict the likelihood of developing high-risk disease states in the early stages of HPV infection is crucial. We hypothesize that the composition of the vaginal microbiome plays a key role in the dynamic changes associated with HPV infection. Thus, the aim of this study is to explore the dynamic changes in microbiome characteristics across different HPV infection outcomes. Methods In this prospective observational cohort study, high-throughput 16S ribosomal RNA (16S rRNA) sequencing technology was employed to comprehensively analyze the characteristics and community composition of the vaginal microbiome (VMB) among 96 Chinese women. Participants were divided into three groups: 1. The persistent infection cohort, consisting of 22 patients with ongoing HPV infections; 2. The transient infection cohort, including 31 patients who had successfully cleared high-risk human papillomavirus (HR-HPV) infections; and 3. The control group, comprising 43 healthy females. Results At the onset of HPV infection, compared to the control group（CG）, the infected group exhibited a lower abundance of Lactobacillus and a significantly higher abundance of Pseudomonas, Bifidobacterium, Limosilactobacillus, Peptostreptococcus, Gardnerella, Prevotella, and Dialister. At the study's endpoint, the abundance of Prevotella in the HPV clearance group（HCG）was significantly higher than the control group, whereas the abundances of Bifidobacterium, Limosilactobacillus, and Peptostreptococcus in the persistent HPV infection group（PHIG） were significantly higher than those in both HC group and control group. Both PHI group and HC group exhibited distinct vaginal microbiome characteristics. The PHI group was characterized by a decrease in Lactobacillus and a significant increase in Bifidobacterium, Limosilactobacillus, and Peptostreptococcus over time. Conversely, the HC group showed an increase in Pseudomonas and a decrease in Prevotella and Peptostreptococcus. Furthermore, KEGG pathway enrichment analysis reveals significant variations in gene functions and metabolic processes, especially in lipid biosynthesis, as HPV infection persists. This increased lipid metabolism suggests that interactions between the virus and host could drive the pathological development and persistence of HPV by altering pathways of lipid synthesis and degradation. Conclusion The observed interplay and mutual regulation between microbial communities suggest that a delicate balance is essential for maintaining cervical health. Disruption of this microbial equilibrium can lead to cervical lesions and potentially result in carcinogenesis. These insights underscore the importance of understanding the microbial ecology within the vaginal environment, as they have profound implications for developing targeted prevention strategies and personalized medical interventions, particularly for high-risk populations. Therefore, maintaining or restoring the microbial balance could be pivotal in preventing cervical pathologies, indicating a promising avenue for future research and clinical applications in the field of gynecological health. Retrospectively registered This study was approved by the Ethics Committee of the Beijing Chaoyang Hospital affiliated with the Capital Medical University (NO.2023-S-415).

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Vaginal Microbial Environment Skews Macrophage Polarization and Contributes to Cervical Cancer Development

Cited by 11 publications

References 25 publications

Gut microbiota dysbiosis promotes the development of epithelial ovarian cancer via regulating Hedgehog signaling pathway

Gut microbiota dysbiosis promotes the development of epithelial ovarian cancer via regulating Hedgehog signaling pathway

HPV‐related cervical diseases: Alteration of vaginal microbiotas and promising potential for diagnosis

Exploring the Vaginal Microbiome's Role in HPV Infection Dynamics: A Prospective Cohort Study

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