Vaginal microbiome composition was demonstrated to be associated with cervical disease. The colonization characteristics
of vaginal microbes and their association with the different cervical disease status, especially cervical cancer (CC), are
rarely investigated. In this cross-sectional study, we characterized the vaginal microbiome of women with different status of
cervical diseases, including 22 NV + (normal tissue with HPV infection), low-grade squamous intraepithelial lesion (LSIL,
n = 45), high-grade squamous intraepithelial lesion (HSIL, n = 36) and CC (n = 27) using bacterial 16S DNA sequencing.
Thirty HPV-negative women with normal tissue were used as the control group. We found that higher diversity of microbiome
with gradual depletion of Lactobacillus, especially L. crispatus, was associated with the severity of cervical disease.
High-risk HPV16 infection was associated with higher microbiome diversity and depletion of Lactobacillus in high-grade
cervical diseases (i.e. HSIL and CC). The CC group was characterized by higher levels of Fannyhessea vaginae, Prevotella,
Bacteroides, Finegoldia, Vibrio, Veillonella, Peptostreptococcus, and Dialister. Co-occurrence network analyses showed that
negative correlations were exclusively observed between Lactobacillus and other bacteria, and almost all non-Lactobacillus
bacteria were positively correlated with each other. In particular, the most diverse and complex co-occurrence network of
vaginal bacteria, as well as a complete loss of L. crispatus, was observed in women with CC. Logistic regression model
identified HPV16 and Lactobacillus as significant risk and protective factors for CC, respectively. These results suggest that
specific Lactobacillus species (e.g. L. crispatus and L. iners) can be used as important markers to target prevention measures
prioritizing HPV16-infected women and other hrHPV-infected women for test, vaccination and treat initiatives.
Citations
Citations to this article as recorded by
Vaginal Microbiome and Pregnancy Complications: A Review Angeliki Gerede, Konstantinos Nikolettos, Eleftherios Vavoulidis, Chrysoula Margioula-Siarkou, Stamatios Petousis, Maria Giourga, Panagiotis Fotinopoulos, Maria Salagianni, Sofoklis Stavros, Konstantinos Dinas, Nikolaos Nikolettos, Ekaterini Domali Journal of Clinical Medicine.2024; 13(13): 3875. CrossRef
Advancements in the Vaginal Microenvironment and Regression of High-Risk Human Papillomavirus Na He, Cunjian Yi, Qingsong Zeng, Wumei Jing, Wenrong He Indian Journal of Microbiology.2024;[Epub] CrossRef
Research Progress on Related Factors of Cervical High-Grade Squamous Intraepithelial Lesions 红颖 王 Advances in Clinical Medicine.2023; 13(12): 20536. CrossRef
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Virulence factor gamma-glutamyltransferase (GGT) of H.
pylori consumes glutamine (Gln) in the stomach to decrease
the tricarboxylic acid metabolite alpha-ketoglutarate (α-kg)
and alter the downstream regulation of α-kg as well as cellular
biological characteristics. Our previous research indicated
that under H. pylori infection, mesenchymal stem cells
(MSCs) migrated to the stomach and participated in gastric
cancer (GC) development either by differentiating into epithelial
cells or promoting angiogenesis. However, how MSCs
themselves participate in H. pylori-indicated GC remains
unclear. Therefore, a GGT knockout H. pylori strain (Hp-
KS-1) was constructed, and downstream histone H3K9 and
H3K27 methylation and the PI3K/AKT signaling pathway
of α-kg were detected using Western blotting. The biological
characteristics of MSCs were also examined. An additive α-kg
supplement was also added to H. pylori-treated MSCs to investigate
alterations in these aspects. Compared to the control
and Hp-KS-1 groups, H. pylori-treated MSCs reduced Gln
and α-kg, increased H3K9me3 and H3K27me3, activated the
PI3K-AKT signaling pathway, and promoted the proliferation,
migration, self-renewal, and pluripotency of MSCs. The
addition of α-kg rescued the H. pylori-induced alterations.
Injection of MSCs to nude mice resulted in the largest tumors
in the H. pylori group and significantly reduced tumor sizes
in the Hp-KS-1 and α-kg groups. In summary, GGT of H.
pylori affected MSCs by interfering with the metabolite α-kg
to increase trimethylation of histone H3K9 and H3K27, activating
the PI3K/AKT signaling pathway, and promoting
proliferation, migration, self-renewal, and pluripotency in tumorigenesis,
elucidating the mechanisms of MSCs in GC
development.
Citations
Citations to this article as recorded by
Gamma-glutamyl transferase secreted by Helicobacter pylori promotes the development of gastric cancer by affecting the energy metabolism and histone methylation status of gastric epithelial cells Xin Jiang, Weijun Wang, Zeyu Wang, Zhe Wang, Huiying Shi, Lingjun Meng, Suya Pang, Mengke Fan, Rong Lin Cell Communication and Signaling.2024;[Epub] CrossRef
Design of a Helicobacter pylori multi-epitope vaccine based on immunoinformatics Man Cui, Xiaohui Ji, Fengtao Guan, Guimin Su, Lin Du Frontiers in Immunology.2024;[Epub] CrossRef
Gastric cancer and mesenchymal stem cell-derived exosomes: from pro-tumorigenic effects to anti-cancer vehicles Maryam Dolatshahi, Ahmad Reza Bahrami, Qaiser Iftikhar Sheikh, Mohsen Ghanbari, Maryam M. Matin Archives of Pharmacal Research.2024; 47(1): 1. CrossRef
Mesenchymal Stem Cell-Derived Exosomes Modulate Angiogenesis in Gastric Cancer Fawzy Akad, Veronica Mocanu, Sorin Nicolae Peiu, Viorel Scripcariu, Bogdan Filip, Daniel Timofte, Florin Zugun-Eloae, Magdalena Cuciureanu, Monica Hancianu, Teodor Oboroceanu, Laura Condur, Radu Florin Popa Biomedicines.2023; 11(4): 1031. CrossRef
Helicobacter pylori and Its Role in Gastric Cancer Victor E. Reyes Microorganisms.2023; 11(5): 1312. CrossRef