Biology subjects

Tribe, R. M.

Publications and source records attributed to Tribe, R. M..

4 recordsLinked to original sources

bioRxiv2025

The maternal inflammatory proteome during pregnancy and its role in predicting the risk of spontaneous preterm birth

BackgroundSpontaneous preterm birth (sPTB) is a significant adverse outcome of pregnancy. Being able to identify and improve the management of those who may be at risk requires robust screening methods. The use of circulating molecular markers provides a promising and non-invasive solution to this problem to allow necessary and successful intervention. The role of inflammation has been continuously demonstrated to play a key role in the onset of sPTB with intrauterine inflammation being a key driver. Here we sought out to explore the inflammatory proteome using a nested case-control approach using samples from pregnant participants in the INSIGHT cohort. ObjectivesTo explore the maternal blood proteome in the second trimester using the Olink Explore panel to identify inflammatory proteins associated with sPTB and assess their predictive value, both independently and in combination with cell-free RNA (cfRNA). Study DesignWe conducted a nested case-control study to investigate inflammatory protein profiles during the second trimester of pregnancy. A total of 138 maternal blood plasma samples were analysed using a targeted proteomic assay quantifying 384 inflammation-related proteins. Differential expression analysis and a LASSO-logistic regression model with Leave-One-Out Cross-Validation (LOOCV) were applied to evaluate the association between inflammatory biomarkers and spontaneous preterm birth (sPTB) outcomes. ResultsUsing predictive modelling of the maternal blood proteome, 16 inflammation-related proteins were identified as key discriminators of sPTB risk, with proteins such as PGF, COL9A1, CST7, CXCL6 and GALNT3 emerging as major contributors for predicting sPTB risk. Using inflammation-related maternal proteins alone to predict sPTB (<35 weeks) achieved an area under the receiver operating characteristic curve (AUC-ROC) of 0.76 (95% CI: 0.66-0.84). The incorporation of both cfRNA and proteomic data into an integrated model, improved the area under the curve to 0.85 (95% CI: 0.78-0.92). The integrated model highlighted inflammatory biomarkers that are not only implicated in preterm birth but also in essential physiological mechanisms such as placental function, tissue remodelling, and extracellular matrix composition, which are critical to maintaining pregnancy and preventing premature labour. ConclusionsThese findings demonstrate that an integrated approach using both cfRNA and proteomic signatures of the second trimester maternal blood plasma yields a more comprehensive biomarker profile for predicting preterm birth risk. This multimodal strategy not only enhances the predictive accuracy but also captures a broader array of biological signals across multiple organ systems. Compared to relying solely on inflammatory proteome markers, this multiomic method offers a deeper molecular characterisation of preterm birth risk in the maternal blood plasma.

systems biology↗

bioRxiv2025

Metabolism of Lactobacillus and Gardnerella vaginalis in vaginal defined media

Lactobacilli and Gardnerella vaginalis are key bacteria within the vaginal microbiota, significantly impacting its chemical environment. Accurately reproducing vaginal bacteria metabolism in vitro is therefore critical in understanding how this may contribute to vaginal health and disease. Complex media such as brain heart infusion (BHI) support the growth of a wide variety of vaginal bacteria but may not accurately reproduce the conditions found in vivo leading to over- or under-representation of important metabolic processes. Here we use a 1H NMR approach to characterise the growth of Lactobacillus crispatus, L. jensenii and a panel of G. vaginalis isolates that differ in their metabolic strategy in a vaginal defined media (VDM). We find that both Lactobacillus species grow well in VDM, produce much more lactate, and consequently acidify the spent culture far more than when cultured in BHI. In contrast, G. vaginalis grows less well in VDM but differences in Bifidobacterium shunt and mixed acid fermentation, previously observed in BHI and evidenced by formate production, are preserved. Importantly neither species consume the available glucose but nevertheless conduct carbohydrate fermentation, implicating a preference for glycogen over glucose metabolism with glucose release evidence of glycogen breakdown. While further work is needed to develop media that can support the growth of a wider variety of vaginal bacteria species and recapitulate all features of their metabolism, VDM nevertheless accurately models the key aspects of the chemical environment when Lactobacillus dominate, and G. vaginalis is prevalent, in the microbiota.

microbiology↗

bioRxiv2021

NMR metabolomics of symbioses between bacterial vaginosis associated bacteria

Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome, characterised by low levels of lacto-bacilli and overgrowth of a diverse group of bacteria, and associated with higher risk of a variety of infections, surgical complications, cancer and spontaneous preterm birth (PTB). Despite the lack of a consistently applicable aetiology, Prevotella spp. are often associated with both BV and PTB and P. bivia has known symbiotic relationships with both Peptostreptococcus anaerobius and Gardnerella vaginalis. Higher risk of PTB can also be predicted by a composite of metabolites linked to bacterial metabolism but their specific bacterial source remains poorly understood. Here we characterise diversity of metabolic strategies among BV associated bacteria and lactobacilli and the symbiotic metabolic relationships between P. bivia and its partners and show how these influence the availability of metabolites associated with BV/PTB and/or pro- or anti-inflammatory immune responses. We confirm a commensal relationship between Pe. anaerobius and P. bivia, refining its mechanism; P. bivia supplies tyrosine, phenylalanine, methionine, uracil and proline, the last of which leads to a substantial increase in overall acetate production. In contrast, our data indicate the relationship between P. bivia and G. vaginalis strains, with sequence variant G2, is mutualistic with outcome dependent on the metabolic strategy of the G. vaginalis strain. Seven G. vaginalis strains could be separated according to whether they performed mixed acid fermentation (MAF) or bifid shunt (BS). In co-culture, P. bivia supplies all G. vaginalis strains with uracil and received substantial amounts of asparagine in return. Acetate production, which is lower in BS strains, then matched that of MAF strains while production of aspartate increased for the latter. Taken together, our data show how knowledge of inter- and intra-species metabolic diversity and the effects of symbiosis may refine our understanding of the mechanism and approach to risk prediction in BV and/or PTB.

microbiology↗

bioRxiv2021

The legacy of maternal SARS-CoV-2 infection on the immunology of the neonate

Despite extensive and ongoing studies of SARS-CoV-2 and evidence that pregnant women are at increased risk of severe COVID-19, the effect of maternal infection on the developing infant remains unclear. To determine the potential impact of exposure to SARS-CoV-2 in utero on the neonate, we have assessed the immunological status of infants born to mothers with confirmed SARS-CoV-2 infection during gestation. No evidence of vertical transmission of SARS-CoV-2 was observed, but transfer of maternal SARS-CoV-2 specific IgG to infants was apparent, although to a lesser extent in cases of active or recent maternal infection. Infants born to mothers with recent/ongoing infection had elevated circulating pro-inflammatory cytokines and enhanced percentages of innate immune cells compared to that seen in infants born to uninfected mothers. In tandem, higher frequencies of FOXP3+ regulatory T cells and circulating IL-10 demonstrated a further nuance to the neonatal effector response. Interestingly, cytokine functionality was enhanced in infants born to mothers exposed to SARS-CoV-2 at any time during pregnancy. This indicates that maternal SARS-CoV-2 infection influences in utero priming of the fetal immune system.

immunology↗