Localized microbially induced inflammation influences distant healthy tissues in the human oral cavity.

Variation in human immune response to the same bacterial or viral pathogen is well established in the literature. Variation in immune response to microbial challenge has also been observed within the human oral cavity. Our recent study focused on characterizing observed variations in microbially induced gingival inflammation-resulting in three distinct clinical Inflammatory Responder Types (IRTs): High-IRT, Low-IRT, and Slow-IRT.

Does Oral Endotoxin Contribute to Systemic Inflammation?

The oral microbiome, with a unique emphasis on has been associated with a constellation of inflammatory diseases such as cardiovascular disease, rheumatoid arthritis, Alzheimer's disease, type II diabetes, and non-alcoholic associated fatty liver disease. Periodontal disease has also been shown to induce "leaky gut" leading to metabolic endotoxemia. Several recent studies investigating the habitants of the blood microbiome have found the majority of species appear to be derived from oral and skin bacterial communities in otherwise healthy individuals.

Macrophage migration inhibitory factor regulates specific innate immune sensor responses in gingival epithelial cells.

Background: The gingival epithelium protects periodontal tissues and the alveolar bone by maintaining a steady state of regulated inflammatory surveillance, also known as healthy homeostasis. Accordingly, the repertoire of receptors present within the gingival epithelium showcases its ability to recognize microbial colonization and contribute to bacterial sensing. Macrophage migration inhibitory factor (MIF) is one of many cytokines that are expressed in this protective state and is involved in neutrophil regulation.

Commensal oral microbiota induces osteoimmunomodulatory effects separate from systemic microbiome in mice.

Commensal microbes critically regulate skeletal homeostasis, yet the impact of specific microbiota communities on osteoimmune response mechanisms is unknown. To discern osteoimmunomodulatory effects imparted by the commensal oral microbiota that are distinct from the systemic microbiota, osteoimmunology studies were performed in both alveolar bone and nonoral skeletal sites of specific pathogen-free (SPF) versus germ-free (GF) mice and SPF mice subjected to saline versus chlorhexidine oral rinses. SPF versus GF mice had reduced cortical/trabecular bone and an enhanced pro-osteoclastic phenotype in alveolar bone.

Clinically Healthy Human Gingival Tissues Show Significant Inter-individual Variability in GCF Chemokine Expression and Subgingival Plaque Microbial Composition.

Clinically healthy gingival tissue is maintained through controlled regulation of host defense mechanisms against plaque biofilm overgrowth. One key component is the transit of neutrophils from the vasculature into gingival tissue where the expression of different neutrophil chemokines are tightly regulated. This cross-sectional study examines the inter-individual variability in chemokine profiles within gingival crevicular fluid (GCF) in relation to the subgingival bacterial community in a state of gingival health.

Genomic and functional characterization of a mucosal symbiont involved in early-stage colorectal cancer.

Colorectal cancer is a major health concern worldwide. Growing evidence for the role of the gut microbiota in the initiation of CRC has sparked interest in approaches that target these microorganisms. However, little is known about the composition and role of the microbiota associated with precancerous polyps.

Human variation in gingival inflammation.

Oral commensal bacteria actively participate with gingival tissue to maintain healthy neutrophil surveillance and normal tissue and bone turnover processes. Disruption of this homeostatic host-bacteria relationship occurs during experimental gingivitis studies where it has been clearly established that increases in the bacterial burden increase gingival inflammation. Here, we show that experimental gingivitis resulted in three unique clinical inflammatory phenotypes (high, low, and slow) and reveal that interleukin-1β, a reported major gingivitis-associated inflammatory mediator, was not associated with clinical gingival inflammation in the slow response group.

Influence of Bacterial Profiles in Cytokine and Clinical Features of Endodontic Disease.

Introduction: We verified the association between selected bacterial profiles and levels of cytokines, chemokines, and the expression of signs and symptoms of primary endodontic infection with apical periodontitis.

Methods: Samples were collected from 21 root canals, and macrophages were stimulated for 24 hours. Tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-10, IL-12p70, interferon gamma, and chemokine (C-C motif) ligand 2 (CCL2) were measured using cytometric bead array.

Oral biofilms revisited: A novel host tissue of bacteriological origin.

The central theme of this volume of Periodontology 2000 is that the microbial dental plaque biofilm, specifically the subgingival dental plaque biofilm, mimics a human tissue in both structure and function. As a basis for this assertion we use the definition of a tissue as an aggregate of similar cells and cell products forming a defined structure with a specific function, in a multicellular organism. Accordingly, we propose that the dental plaque biofilm represents an acquired human tissue largely of bacterial origin that maintains the health of gingival tissue.

Maintaining homeostatic control of periodontal epithelial tissue.

Years of coevolution with resident microbes has made them an essential component of health. Yet, little is known about oral commensal bacteria's contribution to and role in the maintenance of oral health and homeostasis. Commensal bacteria are speculated to play a host protective role in the maintenance of health.

An Ayurvedic Herbal Extract Inhibits Biofilm Formation and Disrupts Preformed Biofilms .

Objective: Sudantha® (SUD), a natural proprietary mixture of herbal extracts that has been incorporated into toothpaste, has been shown in two separate placebo controlled human clinical studies to promote gingival health; and reduce gingival bleeding and plaque formation. However, the herbal based anti-gingivitis mechanisms of Sudantha are not fully understood. The objective of this study was to determine the effect of Sudantha on dental plaque biofilms by investigating its effect on mono-culture biofilms of a primary colonizer, , .

Microbial Lipid A Remodeling Controls Cross-Presentation Efficiency and CD8 T Cell Priming by Modulating Dendritic Cell Function.

The majority of Gram-negative bacteria elicit a potent immune response via recognition of lipid A expressed on the outer bacterial membrane by the host immune receptor Toll-like receptor 4 (TLR4). However, some Gram-negative bacteria evade detection by TLR4 or alter the outcome of TLR4 signaling by modification of lipid A species. Although the role of lipid A modifications on host innate immunity has been examined in some detail, it is currently unclear how lipid A remodeling influences host adaptive immunity.

An Ayurvedic herbal extract inhibits oral epithelial cell IL-8 responses to host and bacterial agonists.

Background: Natural products constitute a promising class of therapeutics for the treatment of gingivitis and periodontitis as well as the maintenance of oral health. However, the limited understanding behind their potential mechanisms and modes of action have hampered their incorporation into popular western therapeutics. This in vitro study characterizes an Ayurvedic herbal extract mixture, which has been clinically shown to promote gingival health and homeostasis.

Gingival Epithelial Cell Recognition of Lipopolysaccharide.

Gingival epithelium plays a pivotal role in protecting the underlying periodontium from the microbial colonization found in the gingival sulcus. Having an appropriate phenotype displayed by gingival epithelial cells is a critical host component required for protection against bacterial invasion into gingival tissues. In the present study, gingival epithelial homeostasis associated with the CXCL-8/IL-8 chemokine response was investigated in vitro to determine the mechanisms that gingival epithelial cells utilize for sensing gram-positive and gram-negative microorganisms.

The Distinct Immune-Stimulatory Capacities of Porphyromonas gingivalis Strains 381 and ATCC 33277 Are Determined by the Allele and Gingipain Activity.

The strain ATCC 33277 (33277) and 381 genomes are nearly identical. However, strain 33277 displays a significantly diminished capacity to stimulate host cell Toll-like receptor 2 (TLR2)-dependent signaling and interleukin-1β (IL-1β) production relative to 381, suggesting that there are strain-specific differences in one or more bacterial immune-modulatory factors. Genomic sequencing identified a single nucleotide polymorphism in the 33277 allele (A→T), creating a premature stop codon in the 33277 open reading frame relative to the 381 allele.

Toll-like receptor-2 and -4 responses regulate neutrophil infiltration into the junctional epithelium and significantly contribute to the composition of the oral microbiota.

Background: Oral gingival tissue, especially the junctional epithelium (JE), is constantly exposed to sub-gingival plaque. A key component of gingival health is the regulation of the number of neutrophils that migrate into the gingival crevice to counteract its harmful effects. This report investigates the contribution of innate defense receptors, Toll-like receptor (TLR)2, TLR4, and both (TLR2/4) to the maintenance of neutrophil homeostasis in the JE.

Identification of PGN_1123 as the Gene Encoding Lipid A Deacylase, an Enzyme Required for Toll-Like Receptor 4 Evasion, in Porphyromonas gingivalis.

Removal of one acyl chain from bacterial lipid A by deacylase activity is a mechanism used by many pathogenic bacteria to evade the host's Toll-like receptor 4 (TLR4)-mediated innate immune response. In , a periodontal pathogen, lipid A deacylase activity converts a majority of the initially synthesized penta-acylated lipid A, a TLR4 agonist, to tetra-acylated structures, which effectively evade TLR4 sensing by being either inert or antagonistic at TLR4. In this paper, we report successful identification of the gene that encodes the lipid A deacylase enzyme.

The promotion of nephropathy by lipopolysaccharide via toll-like receptors.

Background: Recently, we reported that toll-like receptor (TLR)2 and TLR4 localized on the glomerular endothelium in the glomeruli of streptozotocin (STZ)-induced type 1 diabetic mice and high fat diet feed-induced type 2 diabetic mice, and that periodontal pathogen Porphyromonas gingivalis LPS (Pg-LPS) administration lowered the survival rate of diabetic mice. The present study aims to examine the effect of TLR4 blocking on the suppression of Pg-LPS-induced diabetic nephropathy.

Methods: The survival rate and morphological/biochemical features for streptozotocin-induced diabetic mice with Pg-LPS and TLR4 blocker eritoran administration were investigated by reporter gene assay, urine and blood analysis, immunohistochemistry, and real time-PCR.

3LPS-binding protein and its interactions with P. gingivalis LPS modulate pro-inflammatory response and Toll-like receptor signaling in human oral keratinocytes.

Lipopolysaccharide (LPS)-binding protein (LBP) as an acute-phase protein plays a crucial role in innate host response to bacterial challenge. Our previous study shows that LBP expression in human gingiva is associated with periodontal status. Porphyromonas gingivalis is a keystone periodontopathogen, and its LPS with lipid A structural heterogeneity critically accounts for periodontal pathogenesis.

Heterogeneous Porphyromonas gingivalis LPS modulates immuno-inflammatory response, antioxidant defense and cytoskeletal dynamics in human gingival fibroblasts.

Periodontal (gum) disease is a highly prevalent infection and inflammation accounting for the majority of tooth loss in adult population worldwide. Porphyromonas gingivalis is a keystone periodontal pathogen and its lipopolysaccharide (PgLPS) acts as a major virulence attribute to the disease. Herein, we deciphered the overall host response of human gingival fibroblasts (HGFs) to two featured isoforms of tetra-acylated PgLPS1435/1449 and penta-acylated PgLPS1690 with reference to E.

Cardiolipins Act as a Selective Barrier to Toll-Like Receptor 4 Activation in the Intestine.

Unlabelled: Intestinal homeostasis mechanisms must protect the host intestinal tissue from endogenous lipopolysaccharides (LPSs) produced by the intestinal microbiota. In this report, we demonstrate that murine intestinal fecal lipids effectively block Toll-like receptor 4 (TLR4) responses to naturally occurring Bacteroidetes sp. LPS.

Comparison of Fusobacterium nucleatum and Porphyromonas gingivalis Lipopolysaccharides Clinically Isolated from Root Canal Infection in the Induction of Pro-Inflammatory Cytokines Secretion.

The aim of this study was to compare the biological activity of lipopolysaccharides (LPS) purified from Fusobacterium nucleatum and Porphyromonas gingivalis strains, both isolated from primary endodontic infection (PEI) in the levels of IL-1β and TNF-α released by macrophage cells. Moreover, LPS was purified from F. nucleatum and P.

Draft Genome Sequence of Low-Passage Clinical Isolate Porphyromonas gingivalis MP4-504.

We present the draft genome ofPorphyromonas gingivalisMP4-504, a low-passage clinical isolate obtained from a periodontitis patient. The genome is composed of 92 contigs for a length of 2,373,453 bp and a G+C of 48.3%.