Effect of Porphyromonas gingivalis infection on gut dysbiosis and arthritis exacerbation in mouse model

Abstract

Background: Porphyromonas gingivalis (Pg) infection causes periodontal disease and is involved in the exacerbation of rheumatoid arthritis (RA). Gut microbiota dysbiosis has shown strong associations with systemic diseases, including RA, diabetes mellitus, and inflammatory bowel disease, and inoculation of periodontopathogenic bacteria (i.e. Pg) can alter gut microbiota composition. Therefore, this study investigated dysbiosis-mediated arthritis exacerbation by Pg oral inoculation in an experimental arthritis model mouse.Methods: Pg inoculation in the oral cavity twice a week for 6 weeks was performed to induce periodontitis in SKG mice. Concomitantly, a single intraperitoneal (i.p.) injection of laminarin (LA) was administered to induce experimental arthritis (Pg-LA mouse). Citrullinated protein (CP) and IL-6 levels in periodontal, intestinal, and joint tissues, and serum were measured by ELISA. Gut microbiota composition was determined by sequencing the bacterial 16S rRNA after DNA purification of mouse feces. Fecal microbiota transplantation (FMT) was performed by transferring Pg-RA-derived feces to normal SKG mice. The effect of the Pg peptidylarginine deaminase (PgPAD) on the level of citrullinated proteins and arthritis progression were determined using PgPAD knockout mutant.Results: Periodontal alveolar bone loss and IL-6 in gingival tissue were induced by Pg oral infection, as well as severe joint destruction, increased arthritis scores (AS), and IL-6 and CP production in serum, joint, and intestinal tissues. Distribution of Deferribacteres and S24-7 was decreased, while CP was significantly increased in gingival, joint, and intestinal tissues of Pg-inoculated experimental arthritis mice compared to experimental arthritis mice without Pg inoculation. Further, FMT from Pg-inoculated experimental arthritis mice showed the reproduction of donor gut microbiota and resulted in severe joint destruction with increased IL-6 and CP production in joint and intestinal tissues. The avarage AS of FMT from Pg-inoculated experimental arthritis was much higher than that of donor mouse. However, inoculation of the PgPAD knockout mutant inhibited the elevation of arthritis scores, ACPA level in serum and reduced CP amount in gingival, joint, and intestinal tissues compared to Pg wild type inoculation .Conclusion: Pg oral infection affected gut microbiota dysbiosis and joint destruction via increased CP generation.

Raman spectroscopy in cell biology and microbiology

“…P. gingivalis has been identified in the brain of patients affected by the Alzheimer disease [ 426 ] and found to play a key role in exacerbating rheumatoid arthritis. [ 427 ] Raman spectroscopy is capable to analyze the metabolites of microbiome (e.g., extracellular vesicle, fatty acids, lipids, enzymes, and glucans) and has the potential to become a safe, flexible, fast, and highly sensitive tool in diagnostics as compared with other available analytical methods (e.g., NMR and mass spectrometry). In the same context of oral microbiome analysis, this review suggests a solution toward surveillance and characterization of pandemics by showing how different viral strains could be promptly differentiated by Raman spectroscopy.…”

Porphyromonas Gingivalis Infection Induces Synaptic Failure via Increased IL-1β Production in Leptomeningeal Cells

“…They are classified into virulent and avirulent strains [37]. ATCC33277 is a typical avirulent strain that is widely used to establish P. gingivalis infection models [38,39]. Other Gram-negative bacteria, like E. coli, and Gram-positive bacteria, like S.…”