AUTHOR=Eriksson Kaja , Lundmark Anna , Delgado Luis F. , Hu Yue O. O. , Fei Guozhong , Lee Linkiat , Fei Carina , Catrina Anca I. , Jansson Leif , Andersson Anders F. , Yucel-Lindberg Tülay 

TITLE=Salivary Microbiota and Host-Inflammatory Responses in Periodontitis Affected Individuals With and Without Rheumatoid Arthritis

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.841139

DOI=10.3389/fcimb.2022.841139

ISSN=2235-2988

ABSTRACT=<sec><title>Objectives</title><p>Periodontitis 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.</p></sec><sec><title>Methods</title><p>Salivary 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.</p></sec><sec><title>Results</title><p>Differential abundance DESeq2 analyses showed that the four most highly enriched (log2 FC &gt;20) amplicon sequence variants (ASVs) in the non-RA periodontitis group included <italic>Alloprevotella</italic> sp., <italic>Prevotella</italic> sp., <italic>Haemophilus</italic> sp., and <italic>Actinomyces</italic> sp. whereas <italic>Granulicatella</italic> sp., <italic>Veillonella</italic> sp., <italic>Megasphaera</italic> sp., and <italic>Fusobacterium nucleatum</italic> were the most highly enriched ASVs (log2 FC &gt;20) in the RA group. OPLS-DA with log2 FC analyses demonstrated that the top ASVs with the highest importance included <italic>Vampirovibrio</italic> sp. having a positive correlation with non-RA group, and seven ASVs belonging to <italic>Sphingomonas insulae</italic>, <italic>Sphingobium</italic> sp., <italic>Novosphingobium aromaticivorans</italic>, <italic>Delftia acidovorans</italic>, <italic>Aquabacterium</italic> spp. and <italic>Sphingomonas echinoides</italic> 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 <italic>Sphingobium</italic> sp., <italic>Acidovorax delafieldii</italic>, <italic>Novosphingobium</italic> sp., and <italic>Aquabacterium</italic> sp.</p></sec><sec><title>Conclusion</title><p>Our 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.</p></sec>