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Deciphering the complex interplay between microbiota, HPV, inflammation and cancer through cervicovaginal metabolic profiling.

ABSTRACT: BACKGROUND:Dysbiotic vaginal microbiota have been implicated as contributors to persistent HPV-mediated cervical carcinogenesis and genital inflammation with mechanisms unknown. Given that cancer is a metabolic disease, metabolic profiling of the cervicovaginal microenvironment has the potential to reveal the functional interplay between the host and microbes in HPV persistence and progression to cancer. METHODS:Our study design included HPV-negative/positive controls, women with low-grade and high-grade cervical dysplasia, or cervical cancer (n?=?78). Metabolic fingerprints were profiled using liquid chromatography-mass spectrometry. Vaginal microbiota and genital inflammation were analysed using 16S rRNA gene sequencing and immunoassays, respectively. We used an integrative bioinformatic pipeline to reveal host and microbe contributions to the metabolome and to comprehensively assess the link between HPV, microbiota, inflammation and cervical disease. FINDINGS:Metabolic analysis yielded 475 metabolites with known identities. Unique metabolic fingerprints discriminated patient groups from healthy controls. Three-hydroxybutyrate, eicosenoate, and oleate/vaccenate discriminated (with excellent capacity) between cancer patients versus the healthy participants. Sphingolipids, plasmalogens, and linoleate positively correlated with genital inflammation. Non-Lactobacillus dominant communities, particularly in high-grade dysplasia, perturbed amino acid and nucleotide metabolisms. Adenosine and cytosine correlated positively with Lactobacillus abundance and negatively with genital inflammation. Glycochenodeoxycholate and carnitine metabolisms connected non-Lactobacillus dominance to genital inflammation. INTERPRETATION:Cervicovaginal metabolic profiles were driven by cancer followed by genital inflammation, HPV infection, and vaginal microbiota. This study provides evidence for metabolite-driven complex host-microbe interactions as hallmarks of cervical cancer with future translational potential. FUND: Flinn Foundation (#1974), Banner Foundation Obstetrics/Gynecology, and NIH NCI (P30-CA023074).

SUBMITTER: Ilhan ZE

PROVIDER: S-EPMC6604110 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Deciphering the complex interplay between microbiota, HPV, inflammation and cancer through cervicovaginal metabolic profiling.

Ilhan Zehra Esra ZE Łaniewski Paweł P Thomas Natalie N Roe Denise J DJ Chase Dana M DM Herbst-Kralovetz Melissa M MM

EBioMedicine 20190424

<h4>Background</h4>Dysbiotic vaginal microbiota have been implicated as contributors to persistent HPV-mediated cervical carcinogenesis and genital inflammation with mechanisms unknown. Given that cancer is a metabolic disease, metabolic profiling of the cervicovaginal microenvironment has the potential to reveal the functional interplay between the host and microbes in HPV persistence and progression to cancer.<h4>Methods</h4>Our study design included HPV-negative/positive controls, women with ...[more]

PMID: 31027917

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Project description:While the link between the cervicovaginal bacterial microbiome, human papillomavirus (HPV) infection, and cervical cancer is recognized (P. Łaniewski, D. Barnes, A. Goulder, H. Cui, et al., Sci. Rep. 8:7593, 2018, http://dx.doi.org/10.1038/s41598-018-25879-7; A. Mitra, D. A. MacIntyre, Y. S. Lee, A. Smith, et al., Sci. Rep. 5:16865, 2015, http://dx.doi.org/10.1038/srep16865; A. Mitra, D. A. MacIntyre, J. R. Marchesi, Y. S. Lee, et al., Microbiome 4:58, 2016, http://dx.doi.org/10.1186/s40168-016-0203-0; J. Norenhag, J. Du, M. Olovsson, H. Verstraelen, et al., BJOG, 127:171-180, 2020, http://dx.doi.org/10.1111/1471-0528.15854; E. O. Dareng, B. Ma, A. O. Famooto, S. N. Adebamowo, et al., Epidemiol. Infect. 144:123-137, 2016, http://dx.doi.org/10.1017/S0950268815000965; A. Audirac-Chalifour, K. Torres-Poveda, M. Bahena-Roman, J. Tellez-Sosa et al., PLoS One 11:e0153274, 2016, http://dx.doi.org/10.1371/journal.pone.0153274; M. Di Paola, C. Sani, A. M. Clemente, A. Iossa, et al., Sci. Rep. 7:10200, 2017, http://dx.doi.org/10.1038/s41598-017-09842-6), the role of the cervicovaginal virome remains poorly understood. In this pilot study, we conducted metagenomic next-generation sequencing of cervicovaginal lavage specimens to investigate the relationship between the cervicovaginal DNA virome, bacterial microbiome, genital inflammation, and HPV infection. Specific virome alterations were associated with features of the local microenvironment related to HPV persistence and progression to cervical cancer. Cervicovaginal viromes clustered distinctly by genital inflammation state. Genital inflammation was associated with decreased virome richness and alpha diversity and an increased abundance of Anelloviridae species from the genus Alphatorquevirus. Lactobacillus bacteriophages were closely associated with increased Lactobacillus abundance, consistent with phage-host relationships. Interestingly, bacteria-bacteriophage transkingdom interactions were linked to genital inflammation and showed specific interactions with bacterial vaginosis-associated bacteria, including Gardnerella, Prevotella, and Sneathia. Taken together, our results reveal prominent virome interactions with features of the cervicovaginal microenvironment that are associated with HPV and cervical cancer. These findings expand our understanding of the cervicovaginal host-microbiome interactions in women's health. IMPORTANCE HPV infection is an established risk factor for cervical cancer. However, more broadly, the role of the cervicovaginal virome in cervical cancer progression is not well understood. Here, we identified cervicovaginal DNA virome alterations associated with local microenvironment factors (vaginal microbiota and genital inflammation) that influence HPV persistence and progression to cervical cancer. These findings indicate that the cervicovaginal virome plays an important role in women's health.

Project description:This study investigates A. mellifera gut microbiota diversity and enzymatic activities, aiming to utilize identified isolates for practical applications in sustainable crop residue management and soil health enhancement. This study sampled honey bees, analyzed gut bacterial diversity via 16S rRNA gene, and screened isolates for cellulolytic, hemicellulolytic, and pectinolytic activities, with subsequent assessment of enzymatic potential. The study reveals that cellulolytic and hemicellulolytic bacterial isolates, mainly from γ-Proteobacteria, Actinobacteria, and Firmicutes, have significant potential for crop residue management. Some genera, like Aneurinibacillus, Bacillus, Clostridium, Enterobacter, Serratia, Stenotrophomonas, Apilactobacillus, Lysinibacillus, and Pseudomonas, are very good at breaking down cellulose and hemicellulase. Notable cellulose-degrading genera include Cedecea (1.390 ± 0.57), Clostridium (1.360 ± 0.86 U/mg), Enterobacter (1.493 ± 1.10 U/mg), Klebsiella (1.380 ± 2.03 U/mg), and Serratia (1.402 ± 0.31 U/mg), while Aneurinibacillus (1.213 ± 1.12 U/mg), Bacillus (3.119 ± 0.55 U/mg), Enterobacter (1.042 ± 0.14 U/mg), Serratia (1.589 ± 0.05 U/mg), and Xanthomonas (1.156 ± 0.08 U/mg) excel in hemicellulase activity. Specific isolates with high cellulolytic and hemicellulolytic activities are identified, highlighting their potential for crop residue management. The research explores gut bacterial compartmentalization in A. mellifera, emphasising gut physiology's role in cellulose and hemicellulose digestion. Pectinolytic activity is observed, particularly in the Bacillaceae clade (3.229 ± 0.02), contributing to understanding the honey bee gut microbiome. The findings offer insights into microbiome diversity and enzymatic capabilities, with implications for biotechnological applications in sustainable crop residue management. The study concludes by emphasizing the need for ongoing research to uncover underlying mechanisms and ecological factors influencing gut microbiota, impacting honey bee health, colony dynamics, and advancements in crop residue management.

Dataset Information

Deciphering the complex interplay between microbiota, HPV, inflammation and cancer through cervicovaginal metabolic profiling.

Publications

Deciphering the complex interplay between microbiota, HPV, inflammation and cancer through cervicovaginal metabolic profiling.

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