Table 5 Fold change of cervicovaginal fluid metabolites that differ in preterm- vs. term-delivered women at GTP1 (20-22 weeks)

From: Vaginal host immune-microbiome-metabolite interactions associated with spontaneous preterm birth in a predominantly white cohort

Metabolic pathway

Sub-pathway

Metabolite

Preterm/Term fold change (Log2)

p-value

KEGG ID

Function

Alcohols and polyols

Inositol phosphate metabolism;

Phosphatidylinositol signalling system

Phytate

3.477

0.030

C01204

• Complexing agent for the removal of traces of heavy metal ions.

• Hypocalcemic agent.

• Strong chelator of important minerals such as calcium, magnesium, iron, and zinc

• Contribute to mineral deficiencies in developing countries

• Antioxidant and anti-inflammatory68,69,70

Carbonyl compounds

Alkyl-phenyl ketones

Hydroxybupropion

1.591

0.016

NA

Has pro-inflammatory effect at high doses77

Carbohydrates and carbohydrate conjugates

Aminocyclitol glycosides

Gentamicin

1.513

0.034

C00505

• Gentamicin action pathway

• Directly involved in growth, development or reproduction

• Anti-inflammatory action75

Phenylpropanoids

Hydroxycoumarins

Ostruthin

1.315

0.031

NA

• Inhibits LPS-induced iNOS and COX-2 expression

• Reduces nitric oxide and PGE2 production.

• Antimycobacterial activity

• Used to treat inflammatory diseases.

• Attenuates the up-regulation of ICAM-1 mRNA expression and inhibits NF-κB73,74.

Furanocoumarins

Bergapten

1.173

0.035

C01557

• Decreases NF-κB, COX-2, iNOS72

Xanthotoxin

1.173

0.035

C01864

• Reduces iNOS and COX-2 and production of NO and PGE2.

• Reduces TNF-α and IL-6 production and expression

• Inhibits the activation of AP-1 and NF-κB subunits.

• Increases IkB71.

Lipids

Flavonoids

Phloretin

1.185

0.018

C00774

• Anti-inflammatory agent similar to NSAIDs

• Employed in the treatment of vaginal inflammation (vaginitis)66

• Inhibit cell growth and inducing apoptosis

• Inhibitor of eukaryotic urea transporters, blocks VacA-mediated urea and ion transport116,117,118

• a metabolite of Escherichia119

Acacetin

1.020

0.031

C01470

• Inhibits macrophage infiltration and production of NO, iNOS and COX-2 in LPS-induced macrophage cells.

• Tocolytic agent to prevent premature labour64,65

Isobutrin

−1.393

0.020

C08649

• Hepatoprotective and anti-inflammatory agent

• Inhibit PGE2 and MMP 1, 2, 9 and 1081,82,83

Nucleotides

Pyrimidine metabolism

DTMP

1.088

0.017

C00364

• DNA formation79,80

Alkaloids

Purine alkaloid biosynthesis; Purine metabolism

Xanthosine

1.020

0.031

C01762

• RNA damage product probably found at sites of inflammation by nucleobase deamination76

  1. p-values are false discovery rate (FDR) adjusted.
  2. COX-2 cyclooxygenase-2, DNA deoxyribonucleic acid, DTMP deoxythymidine monophosphate, GTP gestational time point, ICAM-1 intercellular adhesion molecule 1, IkB inhibitor of kappa-light-chain-enhancer of activated B cells, iNOS inducible nitric oxide synthase, KEGG Kyoto Encyclopaedia of Genes and Genomes, LPS lipopolysaccharide, MMP matrix metalloproteinase, NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells, NO nitric oxide, NSAIDs nonsteroidal anti-inflammatory drugs, PGE2 prostaglandin E2, RNA ribonucleic acid.
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