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.
Highlights
Positive Negative Menopause status (%)b Pre-menopause Post-menopause Smoking status (%)b No Yes Alcohol-drinking status (%) No Yes Oral contraception use (%)b No Yes
The microbial richness of cervical swabs evaluated at the species level was significantly higher in the CIN2/3-CC group than in the control group, as measured by Chao 1 (p = 0.03), and the number of operational taxonomic units (OTUs) found in the microbiome taxonomic profile (MTP) index (p = 0.017) was higher in the CIN2/3-CC group as well
We compared the diversity indices among the datasets to find whether the control group showed higher species diversity relative to the CIN2/3-CC group
Summary
Positive Negative Menopause status (%)b Pre-menopause Post-menopause Smoking status (%)b No Yes Alcohol-drinking status (%) No Yes Oral contraception use (%)b No Yes. Pipelines predict the gene families that are present in a microbial community along with their relatively abundant pathways and orthologs[18]. Longitudinal studies of the microbiome during the CIN processes using metagenomic sequencing have indicated that host genetic variants can interact with the microbial composition, and that these genetic variants might be more abundant in cancer-cell-related pathways and orthologs[19]. Recent dysbiosis studies have reported that progression of CIN to cancer is often accompanied by increased cervical microbiome diversity[9,20]. We evaluated the microbiome diversity and taxonomic composition along with the related functional pathways and orthologs associated with risk of CINs and cervical cancer
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