Objectives: Severe gum disease is among the most prevalent chronic infection in particular in African-American populations and is associated with complex microbial infection in the sub-gingival cavity. The polybacterial nature of periodontal disease is a risk factor for several various systemic diseases. We have shown that the synthesis of nitric oxide (NO; known to regulate gut motility functions) and NRF2 (transcriptional factor known to regulate several antioxidant genes) mediated Phase II protein expression have been altered in colon specimens of polybacterial-infected (Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Fusobacterium nucleatum) ApoE-/- mice. The gut microbiome plays a vital role in intestinal motility; however, it is unclear whether oral polybacterial DNA is present in colon and how it alters the microbiome and NO; synthesis in this mice animal model. Hypothesis: Polybacterial pathogens alters colon microbial environment thus lead to the dysfunction of NO & NRF2-Phase II mediated colon motility. Specific Aims: 1) To determine whether oral pathogens is found in the colon and 2) to investigate how these pathogens modulate the microbiome of the large intestine (colon). Methods: Colon specimens were obtained from 16 weeks polymicrobial-infected (n=4) and healthy (sham infected; n=4) mice. We have isolated microbial DNA from colon specimens and analyzed them by use of 454 pyrosequencing of 16S RNA genes (UNC Microbial Core facility; NC). Data were analyzed and microbial concentrations were determined in Meharry Medical College, Bioinformatics core labs. P<0.05 was considered as significant between study groups. Results: Through BLAST and RDP analysis, we were able to identify several microbiome (healthy vs. pathogenic) in the colon that belongs to oral and colon microbiome. Polybacterial infection altered (p<0.05) the colon microbial environment. Conclusions: Our studies are the first to demonstrate that polybacterial infection can alter colon microbial environment and this may impact on colon motility. This research project is supported by the "Centers of Excellence" grant funded to the School of Dentistry, Meharry Medical College; Nashville, Tennessee