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Vaginal Microbiome Dysbiosis is Associated with the Different Cervical Disease Status
Yingying Ma , Yanpeng Li , Yanmei Liu , Le Cao , Xiao Han , Shujun Gao , Chiyu Zhang
J. Microbiol. 2023;61(4):423-432.   Published online April 3, 2023
DOI: https://doi.org/10.1007/s12275-023-00039-3
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AbstractAbstract
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.

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  • 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
  • Role of the vaginal microbiome in miscarriage: exploring the relationship
    Marwa Saadaoui, Parul Singh, Osman Ortashi, Souhaila Al Khodor
    Frontiers in Cellular and Infection Microbiology.2023;[Epub]     CrossRef
Gamma-glutamyltransferase of Helicobacter pylori alters the proliferation, migration, and pluripotency of mesenchymal stem cells by affecting metabolism and methylation status
Zeyu Wang , Weijun Wang , Huiying Shi , Lingjun Meng , Xin Jiang , Suya Pang , Mengke Fan , Rong Lin
J. Microbiol. 2022;60(6):627-639.   Published online April 18, 2022
DOI: https://doi.org/10.1007/s12275-022-1575-4
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  • 7 Web of Science
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AbstractAbstract
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
Research Support, Non-U.S. Gov't
Clades of γ-Glutamyltransferases (GGTs) in the Ascomycota and Heterologous Expression of Colletotrichum graminicola CgGGT1, a Member of the Pezizomycotina-only GGT Clade
Marco H. Bello , Lynn Epstein
J. Microbiol. 2013;51(1):88-99.   Published online March 2, 2013
DOI: https://doi.org/10.1007/s12275-013-2434-0
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AbstractAbstract
Gamma-glutamyltransferase (GGT, EC 2.3.2.2) cleaves the γ-glutamyl linkage in glutathione (GSH). Ascomycetes in either the Saccharomycotina or the Taphrinomycotina have one to three GGTs, whereas members of the Pezizomycotina have two to four GGTs. A Bayesian analysis indicates there are three well-supported main clades of GGTs in the Ascomycota. 1) A Saccharomycotina and a Taphrinomycotinaspecific GGT sub-clade form a yeast main clade. This clade has the three relatively well-characterized fungal GGTs: (Saccharomyces cerevisiae CIS2 and Schizosaccharomyces pombe Ggt1 and Ggt2) and most of its members have all 14 of the highly conserved and critical amino acids that are found in GGTs in the other kingdoms. 2) In contrast, a main clade (GGT3) differs in 11 of the 14 highly conserved amino acids that are found in GGTs in the other kingdoms. All of the 44 Pezizomycotina analyzed have either one or two GGT3s. 3) There is a Pezizomycotina-only GGT clade that has two wellsupported sub-clades (GGT1 and GGT2); this clade differs in only two of the 14 highly conserved amino acids found in GGTs in the other kingdoms. Because the Pezizomycotina GGTs differ in apparently critical amino acids from the crosskingdom consensus, a putative GGT from Colletotrichum graminicola, a member of the Pezizomycotina, was cloned and the protein product was expressed as a secreted protein in Pichia pastoris. A GGT enzyme assay of the P. pastoris supernatant showed that the recombinant protein was active, thereby demonstrating that CgGGT1 is a bona fide GGT.

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