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. 2016 Apr 26;11(4):e0153274.
doi: 10.1371/journal.pone.0153274. eCollection 2016.

Cervical Microbiome and Cytokine Profile at Various Stages of Cervical Cancer: A Pilot Study

Astride Audirac-Chalifour  1 , Kirvis Torres-Poveda  1 , Margarita Bahena-Román  1 , Juan Téllez-Sosa  1 , Jesús Martínez-Barnetche  1 , Bernardo Cortina-Ceballos  1 , Guillermina López-Estrada  2 , Karina Delgado-Romero  3 , Ana I Burguete-García  1 , David Cantú  4 , Alejandro García-Carrancá  5 , Vicente Madrid-Marina  1
Affiliations

Cervical Microbiome and Cytokine Profile at Various Stages of Cervical Cancer: A Pilot Study

V体育官网入口 - Astride Audirac-Chalifour et al. PLoS One. .

V体育官网 - Abstract

Cervical cancer (CC) is caused by high-risk human papillomavirus persistence due to the immunosuppressive tumor microenvironment mediated by cytokines. Vaginal microbiota determines the presence of certain cytokines locally. We assessed the association between cervical microbiota diversity and the histopathological diagnosis of each stage of CC, and we evaluated mRNA cervical expression levels of IL-4, IL-6, IL-10, TGF-β1, TNF-α and IFN-γ across the histopathological diagnosis and specific bacterial clusters. We determined the cervical microbiota by high throughput sequencing of 16S rDNA amplicons and classified it in community state types (CST). Mean difference analyses between alpha-diversity and histopathological diagnosis were carried out, as well as a β-diversity analysis within the histological diagnosis. Cervical cytokine mRNA expression was analyzed across the CSTs and the histopathological diagnoses. We found a significant difference in microbiota's diversity in NCL-HPV negative women vs those with squamous intraepithelial lesions (SIL) and CC(p = 0. 006, p = 0. 036). When β-diversity was evaluated, the CC samples showed the highest variation within groups (p<0. 0006) and the largest distance compared to NCL-HPV negative ones (p<0 VSports手机版. 00001). The predominant bacteria in women with normal cytology were L. crispatus and L. iners, whereas for SIL, it was Sneathia spp. and for CC, Fusobacterium spp. We found higher median cervical levels of IL-4 and TGF-β1 mRNA in the CST dominated by Fusobacterium spp. These results suggest that the cervical microbiota may be implicated in cervical cancer pathology. Further cohort studies are needed to validate these findings. .

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

VSports在线直播 - Figures

Fig 1
Fig 1. Community composition of cervical samples at the species level as determined by massively parallel sequencing on the 454 platform.
Unsupervised heatmap of the relative abundance of microbial taxa found in the cervical microbial communities of 29 subjects, based on the Bray Curtis dissimilarity metric. The species present in relative abundance of 1% in at least one sample are listed on the X axis. The first bar on the left side represents the treatment as follows: red–HPV-negative without lesion; blue–HPV-positive without lesion; orange–squamous intraepithelial cervical lesion; green–cervical cancer. CST are depicted in the second left barside; pink–CST III, dominated by Pseudomonas oleovorans; cyan–CST II dominated by L. iners; orange–CST I dominated by L. crispatus; green–CST IV dominated by Sneathia; blue–CST V dominated by G. vaginalis; yellow–CST VIII dominated by Fusobacterium spp.; red–CST VI dominated by S. agalactiae, and purple–CST VII dominated by Fusobacterium necrophorum. Sample names appear on the right side of the graph. The cladograms at the top of the species names indicate the approximate evolutionary relationships between the species. CST: Community State Type. Dx: Histopathological diagnosis.
Fig 2
Fig 2. Community compositions according to histopathological diagnosis groups.
Bar chart of relative abundance of species per group.
Fig 3
Fig 3. Comparison of the Shannon diversity index and the PD whole tree logistic according to the histopathological diagnosis group.
The boxplots show the distribution of the H’ (bit units) and PD values across all the samples.
Fig 4
Fig 4. Beta-diversity of microbial communities by histopathological diagnosis.
A. PCoA profile of the histopathological diagnosis displayed with weighted UniFrac distances. Each figure represents one sample colored according to its histopathological diagnosis. Red circles represent HPV-negative NCL samples; blue squares represent HPV-positive NCL samples; orange triangles represent SIL and green triangles represent CC. A1. Principal component (PC)-1 accounted for 33.44% of the variation in the composition of the microbiota due to the presence of Sneathia spp. and Fusobacterium spp. A2. PC-2 accounted for 26.85% of the variation inthe composition of the microbiota due to the presence of Bifidobacteria spp. and Pseudomonas spp. A3. PC-3 accounted for 10.38% of the variation in the composition of the microbiota due to the presence of Lactobacillus spp. and Streptococcus spp. B. B1. Variation of weighted UniFrac distances within each histological diagnosis group. B2. Variation of weighted UniFrac distances compared with -HPV-negativeNCL.
Fig 5
Fig 5. Cervical cytokine mRNA levels normalized to GAPDH, in NCL versus SIL and in NCL versus CC.
(A) IL-4, (B) IL-6, (C) IL-10, (D) TNFα, (E) IFN-γ, (F) TGF-β1. * p value for the Mann-Whitney test (p = 0.04).
Fig 6
Fig 6. Cervical cytokine mRNA levels normalized to GAPDH per community state type (CST).
(A) IL-4, (B) IL-6, (C) IL-10, (D) TNFα, (E) IFN-γ, (F) TGF-β1. *p value for Kruskal Wallis test (p≤0.05).
Fig 7
Fig 7. INF-γ, IL-4, TGF-β1 and IL-10 expression level per sample in community state type CST I, CST IV and CSTVIII and microbiome composition.
Cervical expression level of INF-γ (A), TGF-β1 (B), IL-4 (C) and IL-10 (D) normalized with GAPDH gen. (E) Microbiome composition in relative abundance.
Fig 8
Fig 8. Suggested mechanism of microbiome changes during immunosuppression development.
The cervical epithelium is represented in each stage of CC as departing from a normal epithelium (left) and its longitudinal change when a HR-HPV infects it and it progresses to SIL and CC. Microbiome composition and diversity is depicted according to the main bacteria per stage. Lactobacillus are represented as purple rectangles, Pseudomonas oleovorans as red rectangles, Fusobacterium and Sneathia as shaped rods, Streptococcus agalactieas purple circles, and HPV as blue circles. After infection takes place, the microbiome changes and its diversity increases. HPV proteins E2, E6 and E7 enhance IL-10 expression and macrophages type 2 presence. The latter is also enhanced by TGFβ-1, which is in turn stimulated by the microbiota present. The diversity of the microbiota increases, through its toxins (FadA from Fusobacterium spp.), which disturb tight junctions and promote a metastasis similar to colon carcinoma.
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References

    1. Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, et al. The GlobalBurden of Cancer2013. JAMA Oncol 2015;1(4):505–27. 10.1001/jamaoncol.2015.0735 - DOI - PMC - PubMed
    1. INEGI 2012. Estadísticas de mortalidad. Cubos dinámicos y CONAPO 2012. Proyecciones de la población de México 2012–2050.
    1. Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003, 348:518–27. 10.1056/NEJMoa021641 - DOI (VSports) - PubMed
    1. Gillet E, Meys JF, Verstraelen H, Bosire C, De Sutter P, Temmerman M, et al. Bacterial vaginosis is associated with uterine cervical human papillomavirus infection: a meta-analysis. BMC Infect Dis 2011, 11:10 10.1186/1471-2334-11-10 - DOI - PMC - PubMed
    1. Guo YL, You K, Qiao J, Zhao YM, Geng L. Bacterial vaginosis is conducive to the persistence of HPV infection. Int J STD AIDS 2012;23(8):581–4. 10.1258/ijsa.2012.011342 - DOI - PubMed

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