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

Luz Amparo Gómez,Juliette De Avila,Gloria Inés Lafaurie,Tammy Gorety Trujillo,Diana Marcela Castillo,Daniel Antonio Montenegro,Lina J Suárez

doi:10.3389/fmicb.2020.591626

Luz Amparo Gómez, Juliette De Avila + Show 5 more

Open Access

https://doi.org/10.3389/fmicb.2020.591626

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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.

Highlights

Given the concept that the uterus is a sterile microenvironment, the description of the presence of a healthy microbiome, typical of the placenta, has been widely debated since 2014 by different studies, both in favor (Aagaard et al, 2014; Doyle et al, 2014; Parnell et al, 2017; Seferovic et al, 2019) and against the hypothesis (Leiby et al, 2018; Theis et al, 2019)
Oral clinical assessment showed periodontitis presence in group 2 (P. gingivalis-related placental infection (PI) with adverse pregnancy outcomes (APO)), group 3 (P. gingivalisrelated PI without APO) and group 4 (UGM-related PI with APO; Table 1), all of them associated with P. gingivalis presence in subgingival plaque (60, 75, and 40% respectively; Supplementary Table 1)
In Patients with subgingival presence of P. gingivalis higher indices were more frequent and the highest median was observed in the P. gingivalis-related PI without APO which presented a higher frequency of periodontitis (p < 0.05)

Summary

Introduction

Given the concept that the uterus is a sterile microenvironment, the description of the presence of a healthy microbiome, typical of the placenta, has been widely debated since 2014 by different studies, both in favor (Aagaard et al, 2014; Doyle et al, 2014; Parnell et al, 2017; Seferovic et al, 2019) and against the hypothesis (Leiby et al, 2018; Theis et al, 2019). Statistical analyses of APO associated with intra-amniotic infection by certain microorganisms, have established that intra-amniotic infection may be, one of the main risk factors for PTB, and a direct cause by the force, temporality and the gradient with which the DNA of microorganisms is associated with PTB (DiGiulio et al, 2008)

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