Multi-Omics Data Integration Reveals Key Variables Contributing to Subgingival Microbiome Dysbiosis-Induced Inflammatory Response in a Hyperglycemic Microenvironment
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Published:2023-05-16
Issue:10
Volume:24
Page:8832
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Lafleur Sarah1, Bodein Antoine2, Mbuya Malaïka Mutombo Joanna1, Mathieu Alban2, Joly Beauparlant Charles2, Minne Xavier1ORCID, Chandad Fatiha1, Droit Arnaud2, Houde Vanessa P.1ORCID
Affiliation:
1. Oral Ecology Research Group (GREB), Faculty of Dentistry, Université Laval, 2420 rue de la Terrasse, Québec, QC G1V 0A6, Canada 2. Molecular Medicine Department, CHU de Québec Research Center, Université Laval, Québec, QC G1V 4G2, Canada
Abstract
Subgingival microbiome dysbiosis promotes the development of periodontitis, an irreversible chronic inflammatory disease associated with metabolic diseases. However, studies regarding the effects of a hyperglycemic microenvironment on host–microbiome interactions and host inflammatory response during periodontitis are still scarce. Here, we investigated the impacts of a hyperglycemic microenvironment on the inflammatory response and transcriptome of a gingival coculture model stimulated with dysbiotic subgingival microbiomes. HGF-1 cells overlaid with U937 macrophage-like cells were stimulated with subgingival microbiomes collected from four healthy donors and four patients with periodontitis. Pro-inflammatory cytokines and matrix metalloproteinases were measured while the coculture RNA was submitted to a microarray analysis. Subgingival microbiomes were submitted to 16s rRNA gene sequencing. Data were analyzed using an advanced multi-omics bioinformatic data integration model. Our results show that the genes krt76, krt27, pnma5, mansc4, rab41, thoc6, tm6sf2, and znf506 as well as the pro-inflammatory cytokines IL-1β, GM-CSF, FGF2, IL-10, the metalloproteinases MMP3 and MMP8, and bacteria from the ASV 105, ASV 211, ASV 299, Prevotella, Campylobacter and Fretibacterium genera are key intercorrelated variables contributing to periodontitis-induced inflammatory response in a hyperglycemic microenvironment. In conclusion, our multi-omics integration analysis unveiled the complex interrelationships involved in the regulation of periodontal inflammation in response to a hyperglycemic microenvironment.
Funder
Biocodex Microbiota Foundation
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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