Periodontal diseases manifest by the formation of deep pockets between the gingiva and teeth where multispecies bacterial biofilms flourish, causing inflammation and bone loss. Epithelial cell receptor alpha v beta 6 integrin that regulates inflammation by activating the anti- inflammatory cytokine transforming growth factor-beta 1, is highly expressed in healthy junctional epithelium that connects the gingiva to the tooth enamel. However, its expression is attenuated in human periodontal disease. Moreover, Itgb6(-/-) mice display increased periodontal inflammation compared to wild-type mice. We hypothesized that bacterial biofilms present in the periodontal pockets suppress alpha v beta 6 integrin levels in periodontal disease and that this change aggravates inflammation. To this end, we generated three-week-old multispecies oral biofilms in vitro and treated cultured gingival epithelial cells ( GECs) with their extracts. The biofilm extracts caused suppression of beta 6 integrin expression and upregulation of pro- inflammatory cytokines, including interleukin-1 beta and - 6. Furthermore, GECs with beta 6 integrin siRNA knockdown showed increased interleukin-1 beta expression, indicating that alpha v beta 6 integrin-deficiency is associated with pro-inflammatory cytokine responsiveness. FSL-1, a synthetic bacterial lipopeptide, also suppressed beta 6 integrin expression in GECs. Therefore, biofilm components, including lipopeptides, may downregulate alpha v beta 6 integrin expression in the pocket epithelium and thus promote epithelial cell-driven proinflammatory response in periodontal disease.