Abstract Certain soil microorganisms have been identified as being not only resistant to polycyclic aromatic hydrocarbons (PAHs) but also capable of metabolizing these compounds. We hypothesized that a subset of oral bacteria may be enriched by the altered oral environment of the tobacco smoker with relatively high levels of PAHs. We identified microorganisms that survived long term in minimal media with PAH as the sole carbon source and showed they were much more likely to be isolated from smokers. To start to determine their contribution to oral health, we measured their level in vivo on two mucosal surfaces. On both gingival and lateral border of the tongue mucosa, a group of bacteria were seen to be at lower relative numbers in those exposed to cigarette smoke, while a minority increased. Three taxons were shown to be enriched on gingiva on the family, Streptococcaceae, or genus level, Staphylococcus and Granulicatella. On tongue, genera Mogibacterium and Dialister were enriched. Of bacteria genera that survived harsh PAH exposure in vitro, one was found at substantial levels in the oral mucosal microbiome. Staphylococcus was enriched approximately 6x in smokers, suggesting that the reason for its increase in smokers is due to its resistance to PAH. We will report on this and other oral microbes that can metabolize PAHs. This study highlights the possibility that the oral microbiome can metabolize PAHs like those in cigarette smoke, resulting in carcinogenic products that may contribute to the cancer process in vivo. Citation Format: Guy R. Adami, Lin Tao, Sylvia Pavlova, Stefan J. Green, Ankur Naqib, Benjamin Salameh, Jessica L. Tang, Joel L. Schwartz. PAH-metabolizing microorganism in the oral cavity of smokers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5145.