Abstract
ObjectivesPeriodontitis and rheumatoid arthritis (RA) are two widespread chronic inflammatory diseases with a previously suggested association. The objective of the current study was to compare the oral microbial composition and host´s inflammatory mediator profile of saliva samples obtained from subjects with periodontitis, with and without RA, as well as to predict biomarkers, of bacterial pathogens and/or inflammatory mediators, for classification of samples associated with periodontitis and RA.MethodsSalivary samples were obtained from 53 patients with periodontitis and RA and 48 non-RA with chronic periodontitis. The microbial composition was identified using 16S rRNA gene sequencing and compared across periodontitis patients with and without RA. Levels of inflammatory mediators were determined using a multiplex bead assay, compared between the groups and correlated to the microbial profile. The achieved data was analysed using PCoA, DESeq2 and two machine learning algorithms, OPLS-DA and sPLS-DA.ResultsDifferential abundance DESeq2 analyses showed that the four most highly enriched (log2 FC >20) amplicon sequence variants (ASVs) in the non-RA periodontitis group included Alloprevotella sp., Prevotella sp., Haemophilus sp., and Actinomyces sp. whereas Granulicatella sp., Veillonella sp., Megasphaera sp., and Fusobacterium nucleatum were the most highly enriched ASVs (log2 FC >20) in the RA group. OPLS-DA with log2 FC analyses demonstrated that the top ASVs with the highest importance included Vampirovibrio sp. having a positive correlation with non-RA group, and seven ASVs belonging to Sphingomonas insulae, Sphingobium sp., Novosphingobium aromaticivorans, Delftia acidovorans, Aquabacterium spp. and Sphingomonas echinoides with a positive correlation with RA group. Among the detected inflammatory mediators in saliva samples, TWEAK/TNFSF12, IL-35, IFN-α2, pentraxin-3, gp130/sIL6Rb, sIL-6Ra, IL-19 and sTNF-R1 were found to be significantly increased in patients with periodontitis and RA compared to non-RA group with periodontitis. Moreover, correlations between ASVs and inflammatory mediators using sPLS-DA analysis revealed that TWEAK/TNFSF12, pentraxin-3 and IL-19 were positively correlated with the ASVs Sphingobium sp., Acidovorax delafieldii, Novosphingobium sp., and Aquabacterium sp.ConclusionOur results suggest that the combination of microbes and host inflammatory mediators could be more efficient to be used as a predictable biomarker associated with periodontitis and RA, as compared to microbes and inflammatory mediators alone.
Highlights
Periodontitis is a microbial-induced chronic inflammatory condition, affecting tooth-supporting structures eventually resulting in tooth loss (Page and Kornman, 1997; Darveau, 2010)
These analyses revealed that phyla Spirochaetes, Tenericutes, and Chloroflexi were more abundant in the upper part of the plot and were more predominant in samples from the non-RA group, which clustered to the top (Figures 1A, B)
We aimed to profile the oral microbiome composition and the hosts inflammatory mediators in saliva samples obtained from RA patients with periodontitis and non-RA subjects with periodontitis, as well as to investigate the different bacteria’s association with inflammatory mediators and their importance in classification of RA/non-RA-periodontitis, using the multivariate machine learning algorithms, OPLSDA and sparse partial least squares discriminant analysis (sPLS-DA)
Summary
Periodontitis is a microbial-induced chronic inflammatory condition, affecting tooth-supporting structures eventually resulting in tooth loss (Page and Kornman, 1997; Darveau, 2010). Severe form of periodontitis, afflicting 8-11% of the population (Kassebaum et al, 2014; Eke et al, 2020) cause tooth loss, but can increase the risk for chronic disorders, such as cardiovascular disease, diabetes, and RA (Hajishengallis, 2015; Hajishengallis and Chavakis, 2021), and may have a role in several other systemic diseases and conditions such as obesity, pancreatic cancer, and Alzheimer’s disease (Falcao and Bullon, 2019). The process of periodontitis is initiated when the biofilm forms in proximity to the gingiva and releases various substances, such as lipopolysaccharide, peptidoglycans and toxins, triggering host response (Page and Kornman, 1997; Pollanen et al, 2012; Yucel-Lindberg and Bage, 2013). The ongoing “battle” of inflammation is measurable locally in the oral samples, and systemically as increased levels of pro-inflammatory mediators have been demonstrated in the blood and saliva samples of patients with periodontitis (Van Dyke, 2009; Tasoulas et al, 2016)
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