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      Taxonomic and Functional Differences in Cervical Microbiome Associated with Cervical Cancer Development

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          Abstract

          The cervical microbiome is associated with cervical cancer risk, but how microbial diversity and functional profiles change in cervical cancer remains unclear. Herein, we investigated microbial-compositional and functional differences between a control group and a high-grade cervical intraepithelial neoplasia and cervical cancer (CIN2/3-CC) group. After retrospective collection of 92 cervical swab samples, we carried out 16S rRNA amplicon sequencing on 50 and 42 samples from the control and CIN2/3-CC groups, respectively. The EzBioCloud pipeline was applied to identify the genomic features associated with the groups using 16S rRNA data. A linear discriminant analysis effect size (LEfSe) was performed to assess the enrichment in the assigned taxonomic and functional profiles. We found a lower richness in the control group relative to the CIN2/3-CC group; however, the β-diversity tended to be similar between the groups. The LEfSe analysis showed that a phylum Sacchaaribacteria_TM7, 11 genera, and 21 species were more abundant in the CIN2/3-CC group and that one uncharacterized Gardnerella species was more abundant only in the control group. Further characterization of the functional pathways using EzBioCloud showed that the 4 KEGG orthologs (Phosphotransferase system [PTS] sucrose-specific IIA, IIB, IIC components and PTS cellubiose-specific IIC component) were involved in the KEGG pathway of starch and sucrose metabolism. The two pathways of folate biosynthesis and oxidative phosphorylation were more abundant in the CIN2/3-CC group. Further confirmation of these results in larger samples can help to elucidate the potential association between the cervical microbiome and cervical cancer.

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          Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation (Review).

          Jie Zheng (2012)
          Metabolic activities in normal cells rely primarily on mitochondrial oxidative phosphorylation (OXPHOS) to generate ATP for energy. Unlike in normal cells, glycolysis is enhanced and OXPHOS capacity is reduced in various cancer cells. It has long been believed that the glycolytic phenotype in cancer is due to a permanent impairment of mitochondrial OXPHOS, as proposed by Otto Warburg. This view is challenged by recent investigations which find that the function of mitochondrial OXPHOS in most cancers is intact. Aerobic glycolysis in many cancers is the combined result of various factors such as oncogenes, tumor suppressors, a hypoxic microenvironment, mtDNA mutations, genetic background and others. Understanding the features and complexity of the cancer energy metabolism will help to develop new approaches in early diagnosis and effectively target therapy of cancer.
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            Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota

            Objective Gastric carcinoma development is triggered by Helicobacter pylori. Chronic H. pylori infection leads to reduced acid secretion, which may allow the growth of a different gastric bacterial community. This change in the microbiome may increase aggression to the gastric mucosa and contribute to malignancy. Our aim was to evaluate the composition of the gastric microbiota in chronic gastritis and in gastric carcinoma. Design The gastric microbiota was retrospectively investigated in 54 patients with gastric carcinoma and 81 patients with chronic gastritis by 16S rRNA gene profiling, using next-generation sequencing. Differences in microbial composition of the two patient groups were assessed using linear discriminant analysis effect size. Associations between the most relevant taxa and clinical diagnosis were validated by real-time quantitative PCR. Predictive functional profiling of microbial communities was obtained with PICRUSt. Results The gastric carcinoma microbiota was characterised by reduced microbial diversity, by decreased abundance of Helicobacter and by the enrichment of other bacterial genera, mostly represented by intestinal commensals. The combination of these taxa into a microbial dysbiosis index revealed that dysbiosis has excellent capacity to discriminate between gastritis and gastric carcinoma. Analysis of the functional features of the microbiota was compatible with the presence of a nitrosating microbial community in carcinoma. The major observations were confirmed in validation cohorts from different geographic origins. Conclusions Detailed analysis of the gastric microbiota revealed for the first time that patients with gastric carcinoma exhibit a dysbiotic microbial community with genotoxic potential, which is distinct from that of patients with chronic gastritis.
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              Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity

              Persistent infection with oncogenic Human Papillomavirus (HPV) is necessary for cervical carcinogenesis. Although evidence suggests that the vaginal microbiome plays a functional role in the persistence or regression of HPV infections, this has yet to be described in women with cervical intra-epithelial neoplasia (CIN). We hypothesised that increasing microbiome diversity is associated with increasing CIN severity. llumina MiSeq sequencing of 16S rRNA gene amplicons was used to characterise the vaginal microbiota of women with low-grade squamous intra-epithelial lesions (LSIL; n = 52), high-grade (HSIL; n = 92), invasive cervical cancer (ICC; n = 5) and healthy controls (n = 20). Hierarchical clustering analysis revealed an increased prevalence of microbiomes characterised by high-diversity and low levels of Lactobacillus spp. (community state type-CST IV) with increasing disease severity, irrespective of HPV status (Normal = 2/20,10%; LSIL = 11/52,21%; HSIL = 25/92,27%; ICC = 2/5,40%). Increasing disease severity was associated with decreasing relative abundance of Lactobacillus spp. The vaginal microbiome in HSIL was characterised by higher levels of Sneathia sanguinegens (P < 0.01), Anaerococcus tetradius (P < 0.05) and Peptostreptococcus anaerobius (P < 0.05) and lower levels of Lactobacillus jensenii (P < 0.01) compared to LSIL. Our results suggest advancing CIN disease severity is associated with increasing vaginal microbiota diversity and may be involved in regulating viral persistence and disease progression.
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                Author and article information

                Contributors
                alrud@ncc.re.kr
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                16 June 2020
                16 June 2020
                2020
                : 10
                : 9720
                Affiliations
                [1 ]ISNI 0000 0004 0628 9810, GRID grid.410914.9, Division of Cancer Epidemiology and Prevention, , National Cancer Center, ; 323, Ilsan-ro, Ilsandong-gu, Goyang-si, 10408 Republic of Korea
                [2 ]ISNI 0000 0004 0628 9810, GRID grid.410914.9, Center for Uterine Cancer, National Cancer Center, ; 323, Ilsan-ro, Ilsandong-gu, Goyang-si, 10408 Republic of Korea
                Author information
                http://orcid.org/0000-0001-5279-4162
                Article
                66607
                10.1038/s41598-020-66607-4
                7297964
                32546712
                3df9c987-2a45-4b17-a6ec-905d9b198c9d
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 3 December 2019
                : 19 May 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100003645, National Cancer Center (NCC);
                Award ID: 1910180
                Award ID: 1810920
                Award ID: 1910180
                Award ID: 1810920
                Award ID: 1910180
                Award ID: 1810920
                Award ID: 1810920
                Award Recipient :
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                © The Author(s) 2020

                Uncategorized
                cervical cancer
                Uncategorized
                cervical cancer

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