Commensal modulation of Peri-implant Microbiome Dysbiosis via Veillonella parvula

点击翻译按钮获取中文摘要

Project Summary Peri-implantitis is a prevalent, destructive, inflammatory disease that leads to loss of jawbone around dental implants and impairments in oral health-related quality of life. It poses a public health concern because bone loss progresses at a rapid rate and does not respond therapeutically to conventional periodontal antibacterial therapies. Multiple human studies have firmly established that implant hygiene and tribocorrosion generate implant degradation products, such as titanium microparticles, which are associated with inflammation in a large fraction of peri-implantitis cases, i.e., Titanium (Ti)-mediated peri-implantitis. While it is well documented that titanium microparticles alter peri-implant immune surveillance primarily by inducing oxidative stress, the effects that these changes have on the peri-implant microbiome have not been adequately investigated. The proposed research aims to investigate the genetic mechanisms employed by Veillonella parvula, a bridging microorganism in oral biofilms, to survive and cross-protect oral pathogens in response to environmental oxidative stress. Our preliminary studies demonstrated that increased free titanium levels in peri-implant plaque are associated with a significant reduction in the biodiversity of the peri-implant biofilms that is coupled with the overgrowth of V. parvula. Strong preliminary data point to an antioxidant catalase enzyme encoded by the katA gene as being a key survival system that enables V. parvula’s survival while most peri-implant commensal bacteria are depleted by Titanium-mediated oxidative burst. Importantly, Veillonella demonstrates widespread mutualism with oral pathogens, such as P. gingivalis and F. nucleatum and its catalase protects the latter from oxidative damage suggesting a community-level regulatory role. In this project, we will determine (i) the exact mechanisms used by V. parvula to survive oxidative stress, (ii) the role of katA and other key antioxidant enzymes in modulating biofilm oxidative tolerance, and (iii) the ability of oral pathogens to leverage Veillonella’s katA to colonize and survive in the oral mucosa soft tissue barrier during Ti- mediated inflammation. The long-term goal of this work is to identify the drivers of microbiome dysbiosis in peri-implantitis and to develop efficacious antimicrobial strategies for the management of peri-implant diseases. The objective of the proposed work is to assess the hypothesis that survival mechanisms of commensal Veillonella spp., which enable their overgrowth in this niche are leveraged by oral pathogens to colonize peri-implant microbial communities and lead to clinical disease. The proposed objective will be completed in two main Aims: 1) to identify how titanium-mediated inflammation promotes V. parvula overgrowth, and 2) to determine the extent to which V. parvula alters polymicrobial infection course in vivo. These findings will provide important insights in the role of oral commensal bacteria in modulating microbiome dysbiosis and will introduce novel therapeutic targets of peri-implantitis treatments.