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Effect of Antibiotics on Gut and Vaginal Microbiomes Associated with Cervical Cancer Development in Mice.

ABSTRACT: Antibiotics affect microbial diversity in the gut, leading to dysbiosis and impaired immunity. However, the impact of antibiotics on microbial communities at other sites, such as vagina is less understood. It is also not clear whether changes induced by antibiotics in both microbiomes affect the development of cervical cancer. In this study, we utilized the murine model to evaluate these questions. We show that oral application of broad-spectrum antibiotics in mice changed not only diversity, but composition and sharing of gut and vaginal microbiomes in mice and influenced cervical cancer development in an orthotopic tumor model. Antibiotics decreased richness and diversity indexes in the gut but increased them in the vagina. Some beneficial taxa, such as Bacteroides, Ruminococcaceae, and Lachnospiraceae increased their abundance in the vagina while other pathogenic species, such as Proteobacteria, were decreased. As a result of the changes, mice with greater richness and diversity of the vaginal microbiome after antibiotics exposure were less likely developed tumors. No association between richness and diversity of the gut microbiome and tumor development was identified.

SUBMITTER: Karpinets TV

PROVIDER: S-EPMC10583130 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Effect of Antibiotics on Gut and Vaginal Microbiomes Associated with Cervical Cancer Development in Mice.

Karpinets Tatiana V TV Solley Travis N TN Mikkelson Megan D MD Dorta-Estremera Stephanie S Nookala Sita S SS Medrano Andrea Y Delgado AYD Petrosino Joseph F JF Mezzari Melissa P MP Zhang Jinghua J Futreal P Andrew PA Sastry K Jagannadha KJ Colbert Lauren E LE Klopp Ann A

Cancer prevention research (Philadelphia, Pa.) 20200911 12

Antibiotics affect microbial diversity in the gut, leading to dysbiosis and impaired immunity. However, the impact of antibiotics on microbial communities at other sites, such as vagina is less understood. It is also not clear whether changes induced by antibiotics in both microbiomes affect the development of cervical cancer. In this study, we utilized the murine model to evaluate these questions. We show that oral application of broad-spectrum antibiotics in mice changed not only diversity, bu ...[more]

PMID: 32917644

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Project description:BackgroundAn increasing number of studies indicate that the gut, cervical, and vaginal microbiota may play crucial roles in the development of cervical cancer (CC). However, the interactions between the microbiota and the host are yet unknown. To address this gap, a systematic review and meta-analysis were conducted to assess the microbiota alterations in a variety of body locations, including the gut and genital tract.MethodsElectronic searches of PubMed, Embase, Web of Science, and the Cochrane Library were conducted to retrieve eligible papers published from January 1, 2014, to January 1, 2024 (PROSPERO: CRD42024554433). This study was restricted to English-language studies reporting on alpha diversity, beta diversity, and relative abundance, as well as on patients with CC whose microbiota had been analyzed via next-generation sequencing technologies. To assess the risk of bias (RoB), we utilized the Newcastle‒Ottawa Quality Assessment Scale (NOS) and the ROBINS-I tool. For the meta-analysis, we employed Review Manager 5.4.ResultsThirty-six eligible studies were included in this review. The Chao1 index (SMD = 0.96, [95% CI: 0.71, 1.21], I2 = 0%) and the Shannon index (SMD = 1.02, [95% CI: 0.53, 1.50], I2 = 85%) values from vaginal samples were significantly greater in patients than in the controls. In the cervical samples, the Shannon index value (SMD = 1.29, [95% CI: 0.61, 1.97], I2 = 93%) significantly increased, whereas the Chao1 index value did not significantly differ (SMD = 0.50, [95% CI: -0.46, 1.46], I2 = 89%). The Shannon index value (SMD = 0.25, [95% CI: -0.22, 0.72], I2 = 38%) did not significantly differ across the gut samples. The majority of studies (19/25) indicated that the patients and noncancer controls differed significantly in terms of beta diversity. Cancer-associated changes were observed, with a dramatic decrease in the Lactobacillus genus and significant increases in pathogenic bacteria, including the Anaerococcus, Peptostreptococcus, Porphyromonas, Prevotella, and Sneathia genera. Additionally, the impact of antineoplastic therapies on microbial diversity was inconsistently reported across several studies.ConclusionThis systematic review elucidates the microbiota alterations associated with the prevalence of CC and its response to anti-tumor therapies, aiming to provide insights for future research directions and precision medicine strategies to enhance women's quality of life.Prospero registrationCRD42024554433.

Project description:Cervical intraepithelial neoplasia (CIN) is a precancerous condition inducing local lesions on the surface of the squamocolumnar junction of the cervix. Despite the role of vaginal microbiota having been under-discussed, the role of the cervical microbiome and the microbial migration across the reproductive tract involved in CIN was limitedly studied. We aimed to synchronously characterize the dysbiosis associated with CIN in both the cervix and vagina in a Chinese population. Profiling of cervical and vaginal microbiota from 60 CIN women and 60 healthy women was conducted. 16S rRNA sequencing was adopted. By comparing the microbial profiles between different parts of the reproductive tract, our results demonstrated an increased shift of microbial diversity in the cervix compared with that in the vagina for the CIN patients, specifically in CIN 1. Less dysbiosis was found between the CIN patients and controls, in either the vagina or cervix. The microbial community may be modulated by the onset of sexual activity, a known clinical risk factor for cervical neoplasia. Distinct patterns of perturbated bacteria were found in the vaginal and cervical microbiota, in which reduced Actinobacteria-related operational taxonomic units (OTUs) and increased Proteobacteria-related OTUs were found in the vagina and cervix, respectively. A good agreement between the direction of the top-significant perturbated OTUs was observed between the vaginal and cervical microbiome, suggesting a potential microbial migration in the reproductive tract. Enriched genera such as Sphingomonas and Stenotrophomonas were found in cervical microbiota-associated CIN. Multivariate analysis revealed Comamonas, Rhizobium, and Pseudomonas as independent genera contributing to CIN in the cervix. In summary, this study revealed the perturbation of microbiota in the presence of CIN and demonstrated a distinct pattern of characteristic bacteria community between the vagina and cervix involved in the development of CIN.

Dataset Information

Effect of Antibiotics on Gut and Vaginal Microbiomes Associated with Cervical Cancer Development in Mice.

Publications

Effect of Antibiotics on Gut and Vaginal Microbiomes Associated with Cervical Cancer Development in Mice.

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