Subgingival lipid A profile and endotoxin activity in periodontal health and disease

Alexander Strachan, Zoe Harrington, Clare McIlwaine, Matthew Jerreat, Louise A. Belfield, Aniko Kilar, Simon K. Jackson, Andrew Foey, Svetislav Zaric*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Regulation of lipopolysaccharide (LPS) chemical composition, particularly its lipid A domain, is an important, naturally occurring mechanism that drives bacteria-host immune system interactions into either a symbiotic or pathogenic relationship. Members of the subgingival oral microbiota can critically modulate host immuno-inflammatory responses by synthesizing different LPS isoforms. The objectives of this study were to analyze subgingival lipid A profiles and endotoxin activities in periodontal health and disease and to evaluate the use of the recombinant factor C assay as a new, lipid A-based biosensor for personalized, point-of-care periodontal therapy. Materials and methods: Subgingival plaque samples were collected from healthy individuals and chronic periodontitis patients before and after periodontal therapy. Chemical composition of subgingival lipid A moieties was determined by ESI-Mass Spectrometry. Endotoxin activity of subgingival LPS extracts was assessed using the recombinant factor C assay, and their inflammatory potential was examined in THP-1-derived macrophages by measuring TNF-α and IL-8 production. Results: Characteristic lipid A molecular signatures, corresponding to over-acylated, bi-phosphorylated lipid A isoforms, were observed in diseased samples. Healthy and post-treatment samples were characterized by lower m/z peaks, related to under-acylated, hypo-phosphorylated lipid A structures. Endotoxin activity levels and inflammatory potentials of subgingival LPS extracts from periodontitis patients were significantly higher compared to healthy and post-treatment samples. Conclusions: This is the first study to consider structure-function-clinical implications of different lipid A isoforms present in the subgingival niche and sheds new light on molecular pathogenic mechanisms of subgingival biofilm communities. Clinical relevance: Subgingival endotoxin activity (determined by lipid A chemical composition) could be a reliable, bacterially derived biomarker and a risk assessment tool for personalized periodontal care.

Original languageEnglish
Pages (from-to)3527-3534
Number of pages8
JournalClinical Oral Investigations
Volume23
Issue number9
DOIs
Publication statusPublished - 1 Sept 2019

ASJC Scopus subject areas

  • General Dentistry

Keywords

  • Biomarker
  • Lipid A
  • Lipopolysaccharide
  • Periodontal diseases
  • Subgingival microbiota

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