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

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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.

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          Periodontitis: from microbial immune subversion to systemic inflammation.

          Periodontitis is a dysbiotic inflammatory disease with an adverse impact on systemic health. Recent studies have provided insights into the emergence and persistence of dysbiotic oral microbial communities that can mediate inflammatory pathology at local as well as distant sites. This Review discusses the mechanisms of microbial immune subversion that tip the balance from homeostasis to disease in oral or extra-oral sites.
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            The placenta harbors a unique microbiome.

            Humans and their microbiomes have coevolved as a physiologic community composed of distinct body site niches with metabolic and antigenic diversity. The placental microbiome has not been robustly interrogated, despite recent demonstrations of intracellular bacteria with diverse metabolic and immune regulatory functions. A population-based cohort of placental specimens collected under sterile conditions from 320 subjects with extensive clinical data was established for comparative 16S ribosomal DNA-based and whole-genome shotgun (WGS) metagenomic studies. Identified taxa and their gene carriage patterns were compared to other human body site niches, including the oral, skin, airway (nasal), vaginal, and gut microbiomes from nonpregnant controls. We characterized a unique placental microbiome niche, composed of nonpathogenic commensal microbiota from the Firmicutes, Tenericutes, Proteobacteria, Bacteroidetes, and Fusobacteria phyla. In aggregate, the placental microbiome profiles were most akin (Bray-Curtis dissimilarity <0.3) to the human oral microbiome. 16S-based operational taxonomic unit analyses revealed associations of the placental microbiome with a remote history of antenatal infection (permutational multivariate analysis of variance, P = 0.006), such as urinary tract infection in the first trimester, as well as with preterm birth <37 weeks (P = 0.001). Copyright © 2014, American Association for the Advancement of Science.
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              Recent studies have highlighted the importance of the human microbiome in health and disease. However, for the most part the mechanisms by which the microbiome mediates disease, or protection from it, remain poorly understood. The keystone-pathogen hypothesis holds that certain low-abundance microbial pathogens can orchestrate inflammatory disease by remodelling a normally benign microbiota into a dysbiotic one. In this Opinion article, we critically assess the available literature that supports this hypothesis, which may provide a novel conceptual basis for the development of targeted diagnostics and treatments for complex dysbiotic diseases.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                02 December 2020
                2020
                : 11
                : 591626
                Affiliations
                [1] 1 Unit of Basic Oral Investigations-UIBO, School of Dentistry, Universidad El Bosque , Bogotá, Colombia
                [2] 2 Cellular and Molecular Immunology Group, School of Dentistry, Universidad El Bosque , Bogotá, Colombia
                [3] 3 School of Medicine, Universidad El Bosque , Bogotá, Colombia
                [4] 4 Basic Science and Oral Medicine Department, School of Dentistry, Universidad Nacional de Colombia , Bogotá, Colombia
                Author notes

                Edited by: Marcelo Freire, J. Craig Venter Institute (La Jolla), United States

                Reviewed by: Adriana Sant’Ana, Universidade de São Paulo, Brazil; Werner Solbach, University of Lübeck, Germany

                This article was submitted to Microbial Immunology, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2020.591626
                7738622
                33343532
                6a30fd39-8b60-403b-913b-6eaca762f5be
                Copyright © 2020 Gómez, De Avila, Castillo, Montenegro, Trujillo, Suárez and Lafaurie.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 05 August 2020
                : 16 November 2020
                Page count
                Figures: 5, Tables: 1, Equations: 0, References: 68, Pages: 13, Words: 10063
                Funding
                Funded by: Universidad El Bosque
                Award ID: PCI-2014-18
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                pregnancy outcome,cytokines,periodontitis,dysbiosis,porphyromonas gingivalis,macrophage,inflammation,placenta

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