Microbial and human transcriptome in vaginal fluid at midgestation: Association with spontaneous preterm delivery.
gene expression profiles
human microbiome
infection
microbial community composition
pregnancy
preterm birth
transcriptome
vagina
Journal
Clinical and translational medicine
ISSN: 2001-1326
Titre abrégé: Clin Transl Med
Pays: United States
ID NLM: 101597971
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
revised:
03
07
2022
received:
28
03
2022
accepted:
08
08
2022
entrez:
14
9
2022
pubmed:
15
9
2022
medline:
17
9
2022
Statut:
ppublish
Résumé
Intrauterine infection and inflammation caused by microbial transfer from the vagina are believed to be important factors causing spontaneous preterm delivery (PTD). Multiple studies have examined the relationship between the cervicovaginal microbiome and spontaneous PTD with divergent results. Most studies have applied a DNA-based 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. 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 <37 + 0 weeks) two term controls were randomized (39 + 0 to 40 + 6 weeks). 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. We found 17 human genes to be differentially expressed (false discovery rate, FDR < 0.05) in the preterm group (n = 48) compared to the term group (n = 96). Gene expression of kallikrein-2 (KLK2), KLK3 and four isoforms of metallothioneins 1 (MT1s) was higher in the preterm group (FDR < 0.05). We found 11 individual bacterial species to be differentially expressed (FDR < 0.05), most with a low occurrence. No statistically significant differences in bacterial load, diversity or microbial community state types were found between the groups. 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.
Sections du résumé
BACKGROUND
Intrauterine infection and inflammation caused by microbial transfer from the vagina are believed to be important factors causing spontaneous preterm delivery (PTD). Multiple studies have examined the relationship between the cervicovaginal microbiome and spontaneous PTD with divergent results. Most studies have applied a DNA-based 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.
METHODS
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 <37 + 0 weeks) two term controls were randomized (39 + 0 to 40 + 6 weeks). 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.
RESULTS
We found 17 human genes to be differentially expressed (false discovery rate, FDR < 0.05) in the preterm group (n = 48) compared to the term group (n = 96). Gene expression of kallikrein-2 (KLK2), KLK3 and four isoforms of metallothioneins 1 (MT1s) was higher in the preterm group (FDR < 0.05). We found 11 individual bacterial species to be differentially expressed (FDR < 0.05), most with a low occurrence. No statistically significant differences in bacterial load, diversity or microbial community state types were found between the groups.
CONCLUSIONS
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.
Identifiants
pubmed: 36103557
doi: 10.1002/ctm2.1023
pmc: PMC9473488
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1023Informations de copyright
© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
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