Low Abundance Fusobacterium Nucleatum Supports Early Pregnancy Development – An In Vitro Study

Abstract

Pregnancy success depends greatly on a balanced immune homeostasis. The detection of bacterial components in the upper reproductive tract in non-pregnant and pregnant women raised questions on its possible beneficial role in reproductive health. The local conditions that allow the presence of bacteria to harmonize with the establishment of pregnancy are still unknown. Among the described bacterial species in endometrial and placental samples, Fusobacterium nucleatum was found. It has been observed that F. nucleatum can induce tumorigenesis in colon carcinoma, a process that shares several features with embryo implantation. We propose that low concentrations of F. nucleatum may improve trophoblast function without exerting destructive responses. Inactivated F. nucleatum and E. coli were incubated with the trophoblastic cell lines HTR8/SVneo, BeWo, and JEG-3. Viability, proliferation, migratory capacity, invasiveness and the secretion of chemokines, other cytokines and matrix metalloproteinases were assessed. The presence of F. nucleatum significantly induced HTR8/SVneo invasion, accompanied by the secretion of soluble mediators (CXCL1, IL-6 and IL-8) and metalloproteinases (MMP-2 and MMP-9). However, as concentrations of F. nucleatum increased, these did not improve invasiveness, hindered migration, reduced cell viability and induced alterations in the cell cycle. Part of the F. nucleatum effects on cytokine release were reverted with the addition of a TLR4 blocking antibody. Other effects correlated with the level of expression of E-cadherin on the different cell lines tested. Low amounts of F. nucleatum promote invasion of HTR8/SVneo cells and induce the secretion of important mediators for pregnancy establishment. Some effects were independent of LPS and correlated with the expression of E-cadherin on trophoblasts.

Fusobacterium nucleatum: An Overview of Evidence, Demi-Decadal Trends, and Its Role in Adverse Pregnancy Outcomes and Various Gynecological Diseases, including Cancers

“…F. nucleatum, although often found in healthy human placentas [65], has by far been the most prevalent bacterium implicated in various APOs in the last 5 years [16,29,66,67]. Chorioamnionitis and preterm birth, the common complications of pregnancy causingsignificant maternal, perinatal, and long-term adverse outcomes, have often been associated with a high abundance of F. nucleatum in the placenta, amniotic fluid and fetal membranes [15,16,25,28,48,50,65,[68][69][70][71][72][73][74].…”

“…This was the first reported case to reveal the practicability of performing 16S rRNA sequencing on formalin-fixed, paraffin-embedded placental tissues (FFPE) in microbiological identification of F. nucleatum and the first to establish the use of this molecular technique in the neonatal death investigation [76]. A study from Germany by Heusler et al [65] proposed that low concentrations of F. nucleatum might promote the invasion of trophoblast cells and induce the secretion of mediators for pregnancy establishment. However, in contrast, unrestrained infections caused by F. nucleatum in early pregnancy might impact placental development.…”

Female reproductive tract-organ axes

“…For example, L. crispatus significantly promoted invasion of the trophoblast cell line ( 34 ). Low amounts of Fusobacterium nucleatum also promoted the invasion of trophoblast cells and induced the secretion of mediators for pregnancy establishment ( 35 ). Further studies in this field are strongly needed to establish adequate reproductive medicine.…”