Transfer of oral bacteria to the fetus during late gestation

Abstract

The fetus develops in a privileged environment, as the placenta serves as both a gateway for nutrients and a barrier for pathogen transfer to the fetus. Regardless, recent evidence suggests the presence of bacterial DNA in both placenta and fetus, and we have reported that DNA and protein from small numbers of bacteria gain access to the fetus from the maternal bloodstream. Other routes of environmental bacterial transfer from the mother to fetus remain unknown, as well as the physiological relevance of their presence. In these experiments, we examine multiple routes by which bacterial cellular components can enter the fetus and the fetal response to influx of bacterial DNA and protein. We inoculated maternal sheep with genetically-labeled S. aureus (Staphylococcus aureus) using three routes: intravenously, orally, and intra-vaginally. The inoculum did not produce sepsis or fever in the ewes, therefore mimicking incidental exposure to bacteria during pregnancy. 3–5 days post inoculation, we assessed the presence of bacterial components in the fetal tissues and analyzed fetal brain tissue to identify any alterations in gene expression. Our results demonstrate that components of bacteria that were introduced into the maternal mouth were detected in the fetal brain and that they stimulated changes in gene expression. We conclude that an oral route of transmission is relevant for transfer of bacterial cellular components to the fetus.

The microbiome of the pregnant uterus in Holstein dairy heifers and cows assessed by bacterial culture and 16S ribosomal RNA gene sequencing

“…We did not test the specific hypothesis that the oral microbiome can be transferred to the pregnancy in our study. The recent demonstration that fluorescently-labeled bacteria that are administered orally, intravenously, or vaginally will populate the ovine fetus during late pregnancy ( Yu et al, 2021 ) clearly demonstrates that exposure of the dam to bacteria through an oral or other route can affect the microbiome of the pregnancy.…”

Oral bacteria, oral health, and adverse pregnancy outcomes

“…A select group of microorganisms, including Aggregatibacter , Campylobacter , Capnocytophaga , Eikenella , Escherichia coli , F. nucleatum , Gemella , Leptotrichia , Neisseria , Peptostreptococcus , Streptococcus , and Veillonella , were detected in the mouse placentas, demonstrating that multiple oral species are capable of oral‐utero translocation 26 . In addition, a recent study found oral Staphylococcus aureus transmitting to fetal sheep brain stimulating changes in gene expression 27 . Detailed mechanistic studies focus mainly on F. nucleatum and Porphyromonas gingivalis (Table 2).…”

“…20,21,24,25 26 In addition, a recent study found oral Staphylococcus aureus transmitting to fetal sheep brain stimulating changes in gene expression. 27 Detailed mechanistic studies focus mainly on F. nucleatum and Porphyromonas gingivalis (Table 2).…”

Life at the borderlands: microbiomes of interfaces critical to One Health

“…A few studies suggest that the maternal gut, vagina, and oral cavity could potentially serve as sources for seeding the foetal microbiome via the placenta during pregnancy (Aagaard et al 2014 , Gomez-Arango et al 2017 , Wang et al 2021a , Hummel et al 2022 , Xiao and Zhao 2023 ). A study in sheep, investigating the routes through which nonpathogenic bacteria can enter the foetus, was unable to recover live bacteria from foetal tissue (Yu et al 2021 ). However, the same study showed that DNA and proteins derived from bacteria introduced into the maternal mouth could be detected in the foetal brain and trigger alterations in foetal gene expression, representing an intriguing avenue of communication between the foetus and its mother’s environment, and a potential mechanism to ready the foetus for ex-utero life.…”