Research of cervical microbiota alterations with human papillomavirus infection status and women age in Sanmenxia area of China

Background Human papillomavirus (HPV) infection is the leading cause of cervical cancer. More and more studies discovered that cervical microbiota (CM) composition correlated with HPV infection and the development of cervical cancer. However, more studies need to be implemented to clarify the complex interaction between microbiota and the mechanism of disease development, especially in a specific area of China. Materials and methods In this study, 16S rDNA sequencing was applied on 276 Thin-prep Cytologic Test (TCT) samples of patients from the Sanmenxia area. Systematical analysis of the microbiota structure, diversity, group, and functional differences between different HPV infection groups and age groups, and co-occurrence relationships of the microbiota was carried out. Results The major microbiota compositions of all patients include Lactobacillus iners, Escherichia coli, Enterococcus faecalis, and Atopobium vaginae at species level, and Staphylococcus, Lactobacillus, Gardnerella, Bosea, Streptococcus, and Sneathia in genus level. Microbiota diversity was found significantly different between HPV-positive (Chao1 index: 98.8869, p < 0.01), unique-268 infected (infections with one of the HPV genotype 52, 56, or 58, 107.3885, p < 0.01), multi-268 infected (infections with two or more of HPV genotype 52, 56, and 58, 97.5337, p = 0.1012), other1 (94.9619, p < 0.05) groups and HPV-negative group (83.5299). Women older than 60 years old have higher microbiota diversity (108.8851, p < 0.01, n = 255) than younger women (87.0171, n = 21). The abundance of Gardnerella and Atopobium vaginae was significantly higher in the HPV-positive group than in the HPV-negative group, while Burkholderiaceae and Mycoplasma were more abundant in the unique-268 group compared to the negative group. Gamma-proteobacteria and Pseudomonas were found more abundant in older than 60 patients than younger groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG) analysis revealed the effects on metabolism by microbiota that the metabolism of cells, proteins, and genetic information-related pathways significantly differed between HPV-negative and positive groups. In contrast, lipid metabolism, signal transduction, and cell cycle metabolism pathway significantly differed between multi-268 and negative groups. Conclusion The HPV infection status and age of women were related to CM’s diversity and function pathways. The complex CM co-occurrent relationships and their mechanism in disease development need to be further investigated.

[1]  Lin Zhang,et al.  Simulated root exudates stimulate the abundance of Saccharimonadales to improve the alkaline phosphatase activity in maize rhizosphere , 2022, Applied Soil Ecology.

[2]  Zonghe Yu,et al.  Environmental filtering dominates bacterioplankton community assembly in a highly urbanized estuarine ecosystem. , 2021, Environmental research.

[3]  T. Kindaichi,et al.  Cometabolism of the Superphylum Patescibacteria with Anammox Bacteria in a Long-Term Freshwater Anammox Column Reactor , 2021, Water.

[4]  Guilian Yang,et al.  Depiction of Vaginal Microbiota in Women With High-Risk Human Papillomavirus Infection , 2021, Frontiers in Public Health.

[5]  K. Hua,et al.  Types and viral load of human papillomavirus, and vaginal microbiota in vaginal intraepithelial neoplasia: a cross-sectional study , 2020, Annals of translational medicine.

[6]  Jie Wu,et al.  Triage human papillomavirus testing for cytology-based cervical screening in women of different ages in primary hospitals , 2020, Medicine.

[7]  Phillip R. Bennett,et al.  The vaginal microbiota and innate immunity after local excisional treatment for cervical intraepithelial neoplasia , 2020, Genome medicine.

[8]  Shan Zheng,et al.  Analysis of Clinicopathological Features of Cervical Mucinous Adenocarcinoma with a Solitary Ovarian Metastatic Mass as the First Manifestation , 2020, Cancer management and research.

[9]  Sarah J. Vancuren,et al.  A Generalist Lifestyle Allows Rare Gardnerella spp. to Persist at Low Levels in the Vaginal Microbiome , 2020, Microbial Ecology.

[10]  Zhaohui Liu,et al.  Distinction between vaginal and cervical microbiota in high-risk human papilloma virus-infected women in China , 2020, BMC microbiology.

[11]  F. Masjedian,et al.  Distribution of Lactobacillus species in Iranian women with both human papillomavirus (HPV) infection and bacterial vaginosis (BV) , 2020 .

[12]  C. Blackwood,et al.  Potential microbial bioindicators of phosphorus mining in a temperate deciduous forest , 2020, Journal of applied microbiology.

[13]  A. Arkin,et al.  Small and mighty: adaptation of superphylum Patescibacteria to groundwater environment drives their genome simplicity , 2020, Microbiome.

[14]  J. Ravel,et al.  The vaginal metabolome and microbiota of cervical HPV‐positive and HPV‐negative women: a cross‐sectional analysis , 2019, BJOG : an international journal of obstetrics and gynaecology.

[15]  F. Dini-Andreote,et al.  Genomic signatures and co‐occurrence patterns of the ultra‐small Saccharimonadia (phylum CPR/Patescibacteria) suggest a symbiotic lifestyle , 2019, Molecular ecology.

[16]  K. Totsche,et al.  Predominance of Cand. Patescibacteria in Groundwater Is Caused by Their Preferential Mobilization From Soils and Flourishing Under Oligotrophic Conditions , 2019, Front. Microbiol..

[17]  M. Xi,et al.  Association between genital mycoplasmas infection and human papillomavirus infection, abnormal cervical cytopathology, and cervical cancer: a systematic review and meta-analysis , 2018, Archives of Gynecology and Obstetrics.

[18]  M. Soares,et al.  Analysis of the cervical microbiome and potential biomarkers from postpartum HIV-positive women displaying cervical intraepithelial lesions , 2017, Scientific Reports.

[19]  D. Cavalieri,et al.  Characterization of cervico-vaginal microbiota in women developing persistent high-risk Human Papillomavirus infection , 2017, Scientific Reports.

[20]  Melis N. Anahtar,et al.  Lactobacillus‐Deficient Cervicovaginal Bacterial Communities Are Associated with Increased HIV Acquisition in Young South African Women , 2017, Immunity.

[21]  J. Marchesi,et al.  The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: what do we know and where are we going next? , 2016, Microbiome.

[22]  R. Fichorova,et al.  The Human Microbiome during Bacterial Vaginosis , 2016, Clinical Microbiology Reviews.

[23]  J. K. Nicholson,et al.  Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity , 2015, Scientific Reports.

[24]  Xiaojie Huang,et al.  Distribution of HPV genotypes in Shanghai women. , 2015, International journal of clinical and experimental pathology.

[25]  S. Seo,et al.  The association of uterine cervical microbiota with an increased risk for cervical intraepithelial neoplasia in Korea. , 2015, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[26]  R. Menon,et al.  Cervical Microbiota in Women with Preterm Prelabor Rupture of Membranes , 2015, PloS one.

[27]  Melis N. Anahtar,et al.  Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract. , 2015, Immunity.

[28]  Jacques Ravel,et al.  Interplay between the temporal dynamics of the vaginal microbiota and human papillomavirus detection. , 2014, The Journal of infectious diseases.

[29]  M. Stemmet,et al.  Anaerobes and Bacterial Vaginosis in Pregnancy: Virulence Factors Contributing to Vaginal Colonisation , 2014, International journal of environmental research and public health.

[30]  Yun-Mi Song,et al.  Association of the Vaginal Microbiota with Human Papillomavirus Infection in a Korean Twin Cohort , 2013, PloS one.

[31]  Jennifer M. Fettweis,et al.  Genomic sequence analysis and characterization of Sneathia amnii sp. nov , 2012, BMC Genomics.

[32]  S. Garland,et al.  Bacterial Vaginosis (BV) Candidate Bacteria: Associations with BV and Behavioural Practices in Sexually-Experienced and Inexperienced Women , 2012, PloS one.

[33]  M. Ulanova,et al.  Expression of integrins and Toll-like receptors in cervical cancer: Effect of infectious agents , 2012, Innate immunity.

[34]  F. Polatti Bacterial Vaginosis, Atopobium vaginae and Nifuratel , 2012, Current clinical pharmacology.

[35]  M. Klimek,et al.  Concomitant infections with human papillomavirus and various mycoplasma and ureaplasma species in women with abnormal cervical cytology. , 2011, Advances in medical sciences.

[36]  Joris Meys,et al.  Bacterial vaginosis is associated with uterine cervical human papillomavirus infection: a meta-analysis , 2011, BMC infectious diseases.

[37]  G. Buck,et al.  Drawing the line between commensal and pathogenic Gardnerella vaginalis through genome analysis and virulence studies , 2010, BMC Genomics.

[38]  Kristen E Pascal,et al.  Atopobium vaginae triggers an innate immune response in an in vitro model of bacterial vaginosis. , 2008, Microbes and infection.

[39]  P. Larsson,et al.  Is Bacterial Vaginosis a Sexually Transmitted Disease? , 1991, International journal of STD & AIDS.

[40]  J. Mahlangu,et al.  Access to Systemic Anticancer Treatment and Radiotherapy Services in Sub-Saharan Africa , 2017 .

[41]  W. Wade,et al.  Bergey’s Manual of Systematic Bacteriology , 2012 .

[42]  J. T. Staley,et al.  The alpha-, beta-, delta-, and epsilonproteobacteria , 2005 .