Comparative Analysis of the Placental Microbiome in Pregnancies with Late Fetal Growth Restriction versus Physiological Pregnancies

Abstract

A comparative analysis of the placental microbiome in pregnancies with late fetal growth restriction (FGR) was performed with normal pregnancies to assess the impact of bacteria on placental development and function. The presence of microorganisms in the placenta, amniotic fluid, fetal membranes and umbilical cord blood throughout pregnancy disproves the theory of the “sterile uterus”. FGR occurs when the fetus is unable to follow a biophysically determined growth path. Bacterial infections have been linked to maternal overproduction of pro-inflammatory cytokines, as well as various short- and long-term problems. Proteomics and bioinformatics studies of placental biomass allowed the development of new diagnostic options. In this study, the microbiome of normal and FGR placentas was analyzed by LC-ESI-MS/MS mass spectrometry, and the bacteria present in both placentas were identified by analysis of a set of bacterial proteins. Thirty-six pregnant Caucasian women participated in the study, including 18 women with normal pregnancy and eutrophic fetuses (EFW > 10th percentile) and 18 women with late FGR diagnosed after 32 weeks of gestation. Based on the analysis of the proteinogram, 166 bacterial proteins were detected in the material taken from the placentas in the study group. Of these, 21 proteins had an exponentially modified protein abundance index (emPAI) value of 0 and were not included in further analysis. Of the remaining 145 proteins, 52 were also present in the material from the control group. The remaining 93 proteins were present only in the material collected from the study group. Based on the proteinogram analysis, 732 bacterial proteins were detected in the material taken from the control group. Of these, 104 proteins had an emPAI value of 0 and were not included in further analysis. Of the remaining 628 proteins, 52 were also present in the material from the study group. The remaining 576 proteins were present only in the material taken from the control group. In both groups, we considered the result of ns prot ≥ 60 as the cut-off value for the agreement of the detected protein with its theoretical counterpart. Our study found significantly higher emPAI values of proteins representative of the following bacteria: Actinopolyspora erythraea, Listeria costaricensis, E. coli, Methylobacterium, Acidobacteria bacterium, Bacteroidetes bacterium, Paenisporsarcina sp., Thiodiazotropha endol oripes and Clostridiales bacterium. On the other hand, in the control group statistically more frequently, based on proteomic data, the following were found: Flavobacterial bacterium, Aureimonas sp. and Bacillus cereus. Our study showed that placental dysbiosis may be an important factor in the etiology of FGR. The presence of numerous bacterial proteins present in the control material may indicate their protective role, while the presence of bacterial proteins detected only in the material taken from the placentas of the study group may indicate their potentially pathogenic nature. This phenomenon is probably important in the development of the immune system in early life, and the placental microbiota and its metabolites may have great potential in the screening, prevention, diagnosis and treatment of FGR.

Evaluating Current Molecular Techniques and Evidence in Assessing Microbiome in Placenta-Related Health and Disorders in Pregnancy

“…Despite technology advancements, bioinformatics analysis remains a challenge. In the study of Stupak et al, proteomics (LC–ESI-MS/MS mass spectrometry) and bioinformatics studies of placental biomass were used [ 85 ]. MASCOT 2.4.1 (Matrix Science, London, UK) was used to search the Uniprot 2019_02 (561,356 sequences; 201,858,328 residues) database with bacterial sequences and a filter to examine the spectrum data.…”

“…In the study of Stupak et al, proteomic and bioinformatic (LC–ESI-MS/MS mass spectrometry) analyses of placental biomass in 18 physiological and 18 FGR pregnancies were conducted [ 85 ]. In the FGR group, the results of significantly higher emPAI values of the proteins representative of the following bacteria were detected: Actinopolyspora erythraea , Listeria costaricensis , E. coli , Methylobacterium , Acidobacteria bacterium , Bacteroidetes bacterium , Paenisporsarcina sp., Thiodiazotropha endol oripes , and Clostridiales bacterium .…”

Intestinal flora and pregnancy complications: Current insights and future prospects

“…Staphylococcus and Lactobacillus in fetal tissues activate memory T cells in fetal mesenteric lymph nodes, demonstrating the importance of microbial exposure in fetal immune priming [270] 2022 16S rRNA sequencing shows the placenta has trace microbiota, varying with pregnancy complications [271] 2023 LC-ESI-MS/MS technology detected many bacterial proteins in placentas from both healthy controls and pregnancies with late FGR [272] Abbreviations: FISH, fluorescence in situ hybridization; LC-ESI-MS/MS, liquid chromatography-electrospray ionization-tandem mass spectrometry; rRNA, ribosomal RNA; SEM, scanning electron microscopy; WGS, whole-genome sequencing.…”

Establecimiento del microbiota intestinal del recién nacido durante la lactancia materna

“…Sin embargo, nueva evidencia sugiere que la microbiota materna tiene un efecto importante en el desarrollo intrauterino y podría tener una interacción más activa en el feto. [8][9][10][11] De lo que si estamos seguros es que el proceso del nacimiento representa una importante fuente de bacterias para el bebé dependiendo de la vía de nacimiento:…”