Porphyromonas gingivalis Placental Atopobiosis and Inflammatory Responses in Women With Adverse Pregnancy Outcomes

Abstract

The microbiome modulates inflammation at the fetal maternal interface on both term and preterm labor. Inflammophilic oral bacteria, such as Porphyromonas gingivalis, as well as urogenital microorganisms (UGM) could translocate to the placenta and activate immune mechanisms in decidual tissue that is associated with adverse pregnancy outcomes (APO). This study establishes the associations between the presence of microbes in the placenta and placental cytokine patterns in women who presented APO, e.g., low birth weight (LBW), preterm premature rupture of membranes (PPROM), preterm birth (PTB) and other clinical signs related to Chorioamnionitis (CA). A total of 40 pregnant women were included in the study and divided into five groups according to placental infection (PI) and APO, as follows: (1) women without PI and without APO (n = 17), (2) women with P. gingivalis-related PI and APO (n = 5), (3) women with P. gingivalis-related PI and without APO (n = 4), (4) women with PI related to UGM and APO (n = 5) and (5) women without PI with APO (n = 9). Obstetric, clinical periodontal status evaluation, and subgingival plaque sampling were performed at the time of delivery. Placental levels of interleukin IL-1β, IL-6, IL-10, IL-15, IL-17A, IL-17F, IL-21, IL-12p70, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 α (MCP-1α), granzyme B, and interferon-γ (IFN-γ) were determined using a multiplex flow cytometry assay. All patients showed a predominant Th-1 cytokine profile related to labor, characterized by IFN-γ overexpression. The analysis by groups suggests that Th-1 profile was trending to maintain cytotoxic cell activity by the expression of IL-15 and granzyme B, except for the group with P. gingivalis-related PI and APO, which exhibited a reduction of IL-10 and IL-17F cytokines (p < 0.05) and a Th-1 profile favoring macrophage activation by MCP-1 production (p < 0.05). This study confirms a pro-inflammatory pattern associated with labor, characterized by a Th-1 profile and the activity of cytotoxic cells, which is enhanced by PI with UGM. However, PI associated with P. gingivalis suggests a switch where the Th-1 profile favors an inflammatory response mediated by MCP-1 and macrophage activity as a mechanistic explanation of its possible relationship with adverse outcomes in pregnancy.

Atopobiosis and Dysbiosis in Ocular Diseases: Is Fecal Microbiota Transplant and Probiotics a Promising Solution?

“…The APOs observed included low birth weight, preterm premature rupture of membranes, preterm birth, and other clinical signs related to chorioamnionitis. [22] These findings suggest microbiome translocation and possibly a hematogenic spread via the blood brain barrier and/or placental circulation. Further studies are imperative to investigate the intraocular microbiome profile in uveitis and the corresponding gut microbiome.…”

“…It created a switch of the Th-1 profile balance toward an inflammatory state, mediated by monocyte chemoattractant protein-1 (MCP-1) and macrophages. [22] These mechanisms manifested clinically as adverse pregnancy outcomes (APOs). The APOs observed included low birth weight, preterm premature rupture of membranes, preterm birth, and other clinical signs related to chorioamnionitis.…”

Periodontal Conditions and Pathogens Associated with Pre-Eclampsia: A Scoping Review

“…In the 2017, the role of periodontal diseases (PD) on adverse pregnancy outcomes was discussed [ 11 ]. PD, classified as a non-communicable disease, is a chronic multifactorial and inflammatory immunological disease of polymicrobial origin resulting from an increase in the pathobionts in the microbiota [ 12 , 13 ]. It should be considered that higher periodontal disease prevalence is found among pregnant women with pre-eclampsia.…”

“…The "Keystone-Pathogen Hypothesis", of which Porphyromonas gingivalis ( P. gingivalis) plays a key role, postulates that specific bacteria in limited quantities can influence the host immune system and switch the microbiota from symbiotic to dysbiotic to induce inflammatory disorder [ 14 ]. The virulence characteristics assigned to these specific periodontal pathogens make them potential contributors in adverse pregnancy outcomes [ 13 , 15 ]. As well, increased proportion of bleeding periodontal sites would induce hematological dissemination of periodontal pathogens and their products, and subsequently would later lead to an immune/inflammatory reaction in the feto-placental unit [ 16 ].…”

Effect of Oral Prophylactic Measures on the Occurrence of Pre-Eclampsia (OP-PE) in High-Risk Pregnant Women: A Cluster Randomized Controlled Trial

“…Individual oral prophylaxis could impact bloodstream entry of periodontal pathogenic bacteria such as Porphyromonas gingivalis , whose action on the placental endothelium is scientifically validated [ 23 ]. This periodontal pathogen is the most common microorganism present during bacteremia in patients with periodontitis [ 24 , 25 ], with the capacity to cause inflammation even if present in insignificant quantities [ 26 ]. It is also the most common microorganism in the amniotic fluid and placental tissue associated with adverse pregnancy outcome [ 27 , 28 ].…”