Integrated metagenomics and metabolomics analysis of third-trimester pregnant women with premature membrane rupture: a pilot study

Abstract

Background: Premature rupture of membranes (PROM) is a major pregnancy complication in China and usually leads to adverse pregnancy outcomes. The major aim of this study was to search for microorganisms and their related metabolites that have direct relationship with PROM.Methods: For vaginal discharge samples, metagenomics sequencing was applied to identify microorganisms that were enriched in PROM subjects, and untargeted metabolomics was applied to characterize the metabolites changes in PROM subjects compared to healthy controls (HC). Correlation analysis was then used to explore the relationship between these microorganisms and metabolites changes.Results: Two upstream metabolites of glycolysis, N-acetyl-D-galactosamine (GalNAc) and sucrose, were found downregulated in the PROM group (P=0.004 and P=0.041, respectively). Higher percentages of conditional pathogens, such as of Streptococcus (8.4% vs. 6.1% in HC group, P=0.15) and Chlamydia (4.3% vs.2.3% in HC group, P=0.07) were found in PROM group. Other common conditional pathogens including Prevotella, Staphylococcus, Mycobacterium and Enterobacter, were also higher in PROM group, although their absolute percentages were low and the differences did not reach statistical significance due to relative small sample size. Correlation analysis further demonstrated a positive correlation of downregulation of glycolysis metabolites with higher percentage of conditional pathogens.Conclusions: Integrated metagenomics and metabolomics analysis can be used to track the subtle changes in the vaginal microenvironment. Downregulation of glycolysis substrates (GalNAc and sucrose) and increase of related pathogenic microorganisms (Streptococcus and Chlamydia) could serve as early warning biomarkers of PROM.

Interactions between microbiota and cervical epithelial, immune, and mucus barrier

“…The metabolite signature of AV is less characterised than that of BV. A study on premature rupture of membranes (PROM) patients shows that the glycolytic metabolite GalNAc (N-acetylgalactosamine) and sucrose negatively correlate with Streptococcus, Chlamydia, Prevotella, Staphylococcus, Mycobacterium, and Enterobacter genera, which supports the reduction of lactic acid (Liu et al, 2021b). In addition, Streptococcus spp.…”

The vaginal microbial signatures of preterm birth woman

“…The poor health care environment in India compared to other regions may have contributed to the high percentage of Enterobacter. In addition, a study found that an increase in Enterobacter in women with premature rupture of membranes was positively correlated with downregulation of glycolytic metabolites [51], which has the potential value. Moreover, a study found that Enterobacter abundance was negatively correlated with gestational age in fetal fecal and may be involved in the inflammatory response that triggers PTB [52].…”

Gain a Baby Lose a Tooth—Is There an Association between Periodontitis and Preterm Birth?

“…Prevotella belongs to the phylum Bacteroidetes, a common periodontal pathogen of the orange complex [ 79 ], and is associated with bacterial vaginosis [ 80 ]. Prevotella and other oral species may impair neutrophil leukocyte function and produce collagenases and fibrinolysins, which may collectively contribute to the induction of preterm birth [ 81 ]. A connection between Prevotella and preterm birth has also been reported in a study investigating the vaginal microbiome and metabolome of women with preterm membrane rupture, which found Prevotella to be among the most abundant species within the preterm membrane rupture group [ 82 ].…”