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Multiple studies have examined the relationship between the cervicovaginal microbiome and spontaneous PTD with divergent results. Most studies have applied a DNA\u2010based assessment, providing information on the microbial composition but not transcriptional activity. A transcriptomic approach was applied to investigate differences in the active vaginal microbiome and human transcriptome at midgestation between women delivering spontaneously preterm versus those delivering at term.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Vaginal swabs were collected in women with a singleton pregnancy at 18 + 0 to 20 + 6 gestational weeks. For each case of spontaneous PTD (delivery\u00a0&lt;37 + 0\u00a0weeks) two term controls were randomized (39 + 0 to 40 + 6\u00a0weeks). Vaginal specimens were subject to sequencing of both human and microbial RNA. Microbial reads were taxonomically classified using Kraken2 and RefSeq as a reference. Statistical analyses were performed using DESeq2. GSEA and HUMAnN3 were used for pathway analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found 17 human genes to be differentially expressed (false discovery rate, FDR\u00a0&lt;\u00a00.05) in the preterm group (<jats:italic>n<\/jats:italic>=\u00a048) compared to the term group (<jats:italic>n<\/jats:italic>=\u00a096). Gene expression of kallikrein\u20102 (KLK2), KLK3 and four isoforms of metallothioneins 1 (MT1s) was higher in the preterm group (FDR\u00a0&lt;\u00a00.05). We found 11 individual bacterial species to be differentially expressed (FDR\u00a0&lt;\u00a00.05), most with a low occurrence. No statistically significant differences in bacterial load, diversity or microbial community state types were found between the groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In our mainly white population, primarily bacterial species of low occurrence were differentially expressed at midgestation in women who delivered preterm versus at term. However, the expression of specific human transcripts including KLK2, KLK3 and several isoforms of MT1s was higher in preterm cases. This is of interest, because these genes may be involved in critical inflammatory pathways associated with spontaneous PTD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1023","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T17:55:24Z","timestamp":1663178124000},"source":"Crossref","is-referenced-by-count":11,"title":["Microbial and human transcriptome in vaginal fluid at midgestation: Association with spontaneous preterm delivery"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4208-8667","authenticated-orcid":false,"given":"Tove","family":"Wikstr\u00f6m","sequence":"first","affiliation":[{"name":"Centre of Perinatal Medicine and Health Department of Obstetrics and Gynecology Institute of Clinical Sciences Sahlgrenska Academy University of Gothenburg Gothenburg Sweden"},{"name":"Department of Obstetrics Region V\u00e4stra G\u00f6taland Sahlgrenska University Hospital Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanna","family":"Abrahamsson","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Facility Sahlgrenska Academy University of Gothenburg Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Bengtsson\u2010Palme","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Institute of Biomedicine Sahlgrenska Academy University of Gothenburg Gothenburg Sweden"},{"name":"Centre for Antibiotic Resistance Research (CARe) at University of Gothenburg Gothenburg Sweden"},{"name":"Division of Systems and Synthetic Biology Department of Biology and Biological Engineering Chalmers University of Technology Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joakim","family":"Ek","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology Department of Physiology Sahlgrenska Academy University of Gothenburg Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pihla","family":"Kuusela","sequence":"additional","affiliation":[{"name":"S\u00f6dra \u00c4lvsborg Hospital Bor\u00e5s Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham","family":"Rekabdar","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Facility Sahlgrenska Academy University of Gothenburg Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lindgren","sequence":"additional","affiliation":[{"name":"Department of Clinical Science Intervention and Technology Karolinska Institutet Stockholm Sweden"},{"name":"Centre for Fetal Medicine Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulla\u2010Britt","family":"Wennerholm","sequence":"additional","affiliation":[{"name":"Centre of Perinatal Medicine and Health Department of Obstetrics and Gynecology Institute of Clinical Sciences Sahlgrenska Academy University of Gothenburg Gothenburg Sweden"},{"name":"Department of Obstetrics Region V\u00e4stra G\u00f6taland Sahlgrenska University Hospital Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Jacobsson","sequence":"additional","affiliation":[{"name":"Centre of Perinatal Medicine and Health Department of Obstetrics and Gynecology Institute of Clinical Sciences Sahlgrenska Academy University of Gothenburg Gothenburg Sweden"},{"name":"Department of Obstetrics Region V\u00e4stra G\u00f6taland Sahlgrenska University Hospital Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lil","family":"Valentin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Sk\u00e5ne University Hospital Malm\u00f6 Sweden"},{"name":"Department of Clinical Sciences Malm\u00f6 Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Hagberg","sequence":"additional","affiliation":[{"name":"Centre of Perinatal Medicine and Health Department of Obstetrics and Gynecology Institute of Clinical Sciences Sahlgrenska Academy University of Gothenburg Gothenburg Sweden"},{"name":"Department of Obstetrics Region V\u00e4stra G\u00f6taland Sahlgrenska University Hospital Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","unstructured":"WHO: recommended definitions terminology and format for statistical tables related to the perinatal period and use of a new certificate for cause of perinatal deaths. 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