{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T18:07:23Z","timestamp":1788631643843,"version":"build-2803163510"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Torquetenovirus (TTV) is a negative sense, single-stranded DNA virus present in many body fluids of apparently healthy individuals. At present, it is considered a non-pathogenic endogenous virus. TTV can be detected in the vagina of pregnant women, its abundance being modulated with the extent of immune system activation. Until now, there is only scarce information regarding the association between TTV and the composition of the vaginal environment. Therefore, this study aimed to assess the presence of TTV in the vaginal ecosystem of a cohort of white women with a normal pregnancy (<jats:italic>n<\/jats:italic> = 60) at different gestational stages (first, second and third trimester) and in 9 subjects suffering a first trimester miscarriage. For each woman, we determined (i) the presence and titer of TTV, (ii) the vaginal bacterial composition by means of Nugent score and 16S rRNA gene sequencing, (iii) the vaginal metabolic profiles through <jats:sup>1<\/jats:sup>H-NMR spectroscopy, and (iv) the vaginal concentration of two pro-inflammatory cytokines (IL-6 and IL-8). More than one third of women were found negative for TTV at all gestational stages. Although not statistically significant, the positivity for TTV dropped from 53.3% in the first to 36.6% in the third trimester. TTV loads varied greatly among vaginal samples, ranging between 2 \u00d7 10<jats:sup>1<\/jats:sup> and 2 \u00d7 10<jats:sup>5<\/jats:sup> copies\/reaction. No difference in TTV prevalence and loads was observed between women with normal pregnancies and miscarriages. The presence of TTV was more common in women with a higher vaginal leucocyte count (<jats:italic>p<\/jats:italic> = 0.02). The levels of IL-6 (<jats:italic>p<\/jats:italic> = 0.02), IL-8 (<jats:italic>p<\/jats:italic> = 0.03), propionate (<jats:italic>p<\/jats:italic> = 0.001) and cadaverine (<jats:italic>p<\/jats:italic> = 0.006) were significantly higher in TTV-positive samples. TTV titer was positively correlated with the concentrations of 4-hydroxyphenyllactate (<jats:italic>p<\/jats:italic> &amp;lt; 0.0001), isoleucine (<jats:italic>p<\/jats:italic> = 0.01) and phenylalanine (<jats:italic>p<\/jats:italic> = 0.04). TTV-positive samples were characterized by a higher relative abundance of <jats:italic>Sneathia<\/jats:italic> (<jats:italic>p<\/jats:italic> = 0.04) and <jats:italic>Shuttleworthia<\/jats:italic> (<jats:italic>p<\/jats:italic> = 0.0009). In addition, a trend toward a decrease of <jats:italic>Lactobacillus crispatus<\/jats:italic> and <jats:italic>Lactobacillus jensenii<\/jats:italic>, and an increase of <jats:italic>Lactobacillus iners<\/jats:italic> was observed for TTV-positive samples. In conclusion, we found that TTV is quite common in women with normal pregnancy outcomes, representing a possible predictor of local immune status.<\/jats:p>","DOI":"10.3389\/fmicb.2022.998849","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T12:52:17Z","timestamp":1662727937000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Torquetenovirus in pregnancy: Correlation with vaginal microbiome, metabolome and pro-inflammatory cytokines"],"prefix":"10.3389","volume":"13","author":[{"given":"Sara","family":"Morselli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Foschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Laghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Zagonari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Patuelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Camboni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Ceccarani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarissa","family":"Consolandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marielle Ezekielle","family":"Djusse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Federica","family":"Pedna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Marangoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Severgnini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio","family":"Sambri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1016\/j.immuni.2015.04.019","article-title":"Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract","volume":"42","author":"Anahtar","year":"2015","journal-title":"Immunity"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e05535","DOI":"10.1016\/j.heliyon.2020.e05535","article-title":"Blood hormones and torque teno virus in peripheral blood mononuclear cells","volume":"6","author":"Brundin","year":"2020","journal-title":"Heliyon"},{"key":"B3","doi-asserted-by":"publisher","first-page":"155223","DOI":"10.1016\/j.cyto.2020.155223","article-title":"Peridialytic serum cytokine levels and their relationship with postdialysis fatigue and recovery in patients on chronic haemodialysis\u2014a preliminary study","volume":"135","author":"Brys","year":"2020","journal-title":"Cytokine"},{"key":"B4","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/nmeth.f.303","article-title":"Correspondence QIIME allows analysis of high throughput community sequencing data Intensity normalization improves color calling in SOLiD sequencing","volume":"7","author":"Caporaso","year":"2010","journal-title":"Nat. Methods"},{"key":"B5","doi-asserted-by":"publisher","first-page":"14095","DOI":"10.1038\/s41598-019-50410-x","article-title":"Diversity of vaginal microbiome and metabolome during genital infections","volume":"9","author":"Ceccarani","year":"2019","journal-title":"Sci. Rep"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1086\/319983","article-title":"High carriage rate of TT virus in the cervices of pregnant women","volume":"32","author":"Chen","year":"2011","journal-title":"Clin. Infect. Dis"},{"key":"B7","doi-asserted-by":"publisher","first-page":"702370","DOI":"10.3389\/fmolb.2021.702370","article-title":"Pre-pregnancy diet and vaginal environment in caucasian pregnant women: an exploratory study","volume":"8","author":"Dall'Asta","year":"2021","journal-title":"Front. Mol. Biosci"},{"key":"B8","doi-asserted-by":"publisher","first-page":"528202","DOI":"10.3389\/fimmu.2020.528202","article-title":"Recent insights on the maternal microbiota: impact on pregnancy outcomes","volume":"11","author":"Di Simone","year":"2020","journal-title":"Front. Immunol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1111\/j.1471-0528.2011.03020.x","article-title":"Aerobic vaginitis in pregnancy","volume":"118","author":"Donders","year":"2011","journal-title":"BJO"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1101\/081257","article-title":"UNOISE2: improved error-correction for Illumina 16S and ITS amplicon sequencing","volume":"81257","author":"Edgar","year":"2016","journal-title":"bioRxiv"},{"key":"B11","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.cmi.2016.04.007","article-title":"Torquetenovirus: the human virome from bench to bedside","volume":"22","author":"Focosi","year":"2016","journal-title":"Clin. Microbiol. Infect"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e0207478","DOI":"10.1371\/journal.pone.0207478","article-title":"Impact of meropenem on Klebsiella pneumoniae metabolism","volume":"13","author":"Foschi","year":"2018","journal-title":"PLoS ONE"},{"key":"B13","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1136\/sti.2003.009134","article-title":"Vaginal leucocyte counts in women with bacterial vaginosis: relation to vaginal and cervical infections","volume":"80","author":"Geisler","year":"2004","journal-title":"Sex. Transm. Infect"},{"key":"B14","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1007\/BF02289756","article-title":"Point biserial correlation coefficient and its generalization","volume":"25","author":"Gupta","year":"1960","journal-title":"Psychometrika"},{"key":"B15","doi-asserted-by":"publisher","first-page":"9716","DOI":"10.1007\/s11357-014-9716-2","article-title":"TTV DNA plasma load and its association with age, gender, and HCMV IgG serostatus in healthy adults","volume":"36","author":"Haloschan","year":"2014","journal-title":"Age (Dordr)"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e0006422","DOI":"10.1128\/msystems.00064-22","article-title":"Cervicovaginal DNA virome alterations are associated with genital inflammation and microbiota composition","volume":"7","author":"Kaelin","year":"2022","journal-title":"mSystems"},{"key":"B17","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.fertnstert.2018.06.036","article-title":"Cervicovaginal microbiota, women's health, and reproductive outcomes","volume":"110","author":"Kroon","year":"2018","journal-title":"Fertil. Sterility"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e0249925","DOI":"10.1371\/journal.pone.0249925","article-title":"Vaginal metabolic profiles during pregnancy: Changes between first and second trimester","volume":"16","author":"Laghi","year":"2021","journal-title":"PLoS ONE"},{"key":"B19","doi-asserted-by":"publisher","first-page":"884272","DOI":"10.3389\/fcimb.2022.884272","article-title":"Altered vaginal microbiota composition correlates with human papillomavirus and mucosal immune responses in women with symptomatic cervical ectopy","volume":"12","author":"L\u00f3pez-Filloy","year":"2022","journal-title":"Front. Cell. Infect. Microbiol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/ismej.2010.133","article-title":"UniFrac: an effective distance metric for microbial community comparison","volume":"5","author":"Lozupone","year":"2011","journal-title":"ISME J"},{"key":"B21","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1002\/rmv.668","article-title":"Human anelloviruses and the central nervous system","volume":"20","author":"Maggi","year":"2010","journal-title":"Rev. Med. Virol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"6891","DOI":"10.1128\/JVI.00273-10","article-title":"Role of hematopoietic cells in the maintenance of chronic human torquetenovirus plasma viremia","volume":"84","author":"Maggi","year":"2010","journal-title":"J Virol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"11999","DOI":"10.1128\/JVI.75.24.11999-12004.2001","article-title":"Dynamics of persistent TT virus infection, as determined in patients treated with alpha interferon for concomitant hepatitis C virus infection","volume":"75","author":"Maggi","year":"2001","journal-title":"J. Virol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e0120979","DOI":"10.1371\/journal.pone.0120979","article-title":"Evaluation of the versant CT\/GC DNA 1.0 assay (kPCR) for the detection of extra-genital Chlamydia trachomatis and Neisseria gonorrhoeae infections","volume":"10","author":"Marangoni","year":"2015","journal-title":"PLoS ONE"},{"key":"B25","doi-asserted-by":"publisher","first-page":"656844","DOI":"10.3389\/fmolb.2021.656844","article-title":"New insights into vaginal environment during pregnancy","volume":"8","author":"Marangoni","year":"2021","journal-title":"Front. Mol. Biosci"},{"key":"B26","doi-asserted-by":"publisher","first-page":"904451","DOI":"10.3389\/fmicb.2022.904451","article-title":"Neutrophils dominate the cervical immune cell population in pregnancy and their transcriptome correlates with the microbial vaginal environment","volume":"13","author":"Mohd Zaki","year":"2022","journal-title":"Front. Microbiol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.jbiosc.2009.10.005","article-title":"Production of 4-hydroxyphenyllactic Acid by Lactobacillus Sp. SK007 Fermentation","volume":"109","author":"Mu","year":"2010","journal-title":"J. Biosci. Bioeng."},{"key":"B28","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1128\/jcm.29.2.297-301.1991","article-title":"Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation","volume":"29","author":"Nugent","year":"1991","journal-title":"J. Clin. Microbiol."},{"key":"B29","unstructured":"OksanenJ\n            BlanchetF. G.\n            KindtR.\n            LegendreP.\n            MinchinP. R\n            O'HaraR. B.\n          Package \u201cVegan\u201d. R Package Version 2.0\u2013102013"},{"key":"B30","doi-asserted-by":"publisher","first-page":"600","DOI":"10.3389\/fmicb.2018.00600","article-title":"Insights into vaginal bacterial communities and metabolic profiles of Chlamydia trachomatis infection: positioning between eubiosis and dysbiosis","volume":"9","author":"Parolin","year":"2018","journal-title":"Front. Microbiol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.jri.2014.03.006","article-title":"The microbiome, parturition, and timing of birth: more questions than answers","author":"Prince","year":"2014","journal-title":"J. Reprod. Immunol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.3390\/pathogens10121546","article-title":"Distribution of ermB, ermF, tet(W), and tet(M) resistance genes in the vaginal ecosystem of women during pregnancy and puerperium","volume":"10","author":"Severgnini","year":"2021","journal-title":"Pathogens"},{"key":"B33","doi-asserted-by":"publisher","first-page":"838405","DOI":"10.3389\/fcimb.2022.838405","article-title":"A Deep Look at the Vaginal Environment During Pregnancy and Puerperium","volume":"12","author":"Severgnini","year":"2022","journal-title":"Front. Cell. Infect. Microbiol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1097\/00002030-200103300-00004","article-title":"Inverse relationship between the titre of TT virus DNA and the CD4 cell count in patients infected with HIV","volume":"15","author":"Shibayama","year":"2001","journal-title":"AIDS"},{"key":"B35","doi-asserted-by":"publisher","first-page":"e00204","DOI":"10.1128\/mBio.00204-15","article-title":"Metabolic signatures of bacterial vaginosis","volume":"6","author":"Srinivasan","year":"2015","journal-title":"mBi"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1271\/bbb.121006","article-title":"Identification of antioxidants produced by Lactobacillus plantarum","volume":"77","author":"Suzuki","year":"2013","journal-title":"Biosci. Biotechnol. Biochem"},{"key":"B37","doi-asserted-by":"publisher","first-page":"2075","DOI":"10.1007\/s43032-020-00227-1","article-title":"Torquetenovirus titer in vaginal secretions from pregnant and postpartum women: association with absence of Lactobacillus crispatus and levels of lactic acid and matrix metalloproteinase-8","volume":"27","author":"Tozetto-Mendoza","year":"2020","journal-title":"Reprod. Sci"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e0262672","DOI":"10.1371\/journal.pone.0262672","article-title":"The vaginal torquetenovirus titer varies with vaginal microbiota composition in pregnant women","volume":"17","author":"Tozetto-Mendoza","year":"2022","journal-title":"PLoS ONE"},{"key":"B39","doi-asserted-by":"publisher","first-page":"5261","DOI":"10.1128\/AEM.00062-07","article-title":"Naive bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy","volume":"73","author":"Wang","year":"2007","journal-title":"Appl. Environ. Microbiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1111\/1471-0528.14390","article-title":"Why do lactobacilli dominate the human vaginal microbiota?","volume":"1024","author":"Witkin","year":"2017","journal-title":"BJOG"},{"key":"B41","doi-asserted-by":"publisher","first-page":"e02242","DOI":"10.1128\/mBio.02242-19","article-title":"vaginal biomarkers that predict cervical length and dominant bacteria in the vaginal microbiomes of pregnant women","volume":"10","author":"Witkin","year":"2019","journal-title":"mBio"},{"key":"B42","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s12905-019-0748-8","article-title":"Current patient perspectives of vulvovaginal candidiasis: incidence, symptoms, management and post-treatment outcomes","volume":"19","author":"Yano","year":"2019","journal-title":"BMC Womens Health"},{"key":"B43","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3390\/metabo9010015","article-title":"Univariate statistical analysis as a guide to 1 HNMR spectra signal assignment by visual inspection","volume":"9","author":"Zhu","year":"2019","journal-title":"Metabolites"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.1128\/JCM.00851-09","article-title":"Quantitative PCR assessments of bacterial species in women with and without bacterial vaginosis","volume":"48","author":"Zozaya-Hinchliffe","year":"2010","journal-title":"J. Clin. Microbiol."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.998849\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T12:52:22Z","timestamp":1662727942000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.998849\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,9]]},"references-count":44,"alternative-id":["10.3389\/fmicb.2022.998849"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2022.998849","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,9]]},"article-number":"998849"}}