Polyphenolic extracts from Diospyros kaki and Vitis vinifera by-products stimulate cytoprotective effects in bacteria-cell host interactions by mediation of transcription factor Nrf2

•Grape and persimmon extracts showed bacterial anti-adhesive effects.•Pomegranate extract reduced Salmonella enterica invasion in Caco-2 cells.•Polyphenols supported binding site occupation of non-pathogenic bacteria.•Extracts reduced IL-6, IL-8 and ROS in E. coli lipopolysaccharide-challenged cells.•Persimmon and grape extracts cell defence mechanisms are Nrf2 dependant. The intestinal and skin epithelium play a strong role against bacterial stimuli which leads to inflammation and oxidative stress when overwhelmed. Polyphenols from fruit-rich diets and by-products show promise against bacterial deleterious effects; however, their antibacterial and health-promoting effects remain understudied. This study aimed to assess the impact of polyphenolic extracts of grape (GrPE), persimmon (PePE) and pomegranate (PoPE) by-products on bacterial pathogen-host interactions, focusing beyond growth inhibition to explore their effects on bacterial adhesion, invasion, and modulation of host responses. The microdilution method, as well as the tetrazolium based MTT cell proliferation and cytotoxicity assay with crystal violet staining were used to identify extracts sub-inhibitory concentrations that interfere with bacterial adhesion, invasion or lipopolysaccharides (LPS) effect on cell hosts without compromising host viability. The cytoprotective effects of extracts were assessed in a knock-down model of nuclear factor erythroid 2-related factor 2 (Nrf2). All extracts demonstrated significant reductions in pathogen adhesion to Caco-2 and HaCaT cells while preserving cellular integrity. Notably, PePE exhibited specific efficacy against Salmonella enterica adhesion, attributed mostly to its gallic acid content, whereas PoPE reduced S. enterica invasion in Caco-2 cells. The extracts supported the prevalence of non-pathogenic and commensal strains of intestinal and skin surfaces, selectively reducing pathogenic adhesion. The extracts mitigated the oxidative stress, enhanced the barrier function, and modulated the pro-inflammatory cytokines in LPS-challenged cells. GrPE, rich in anthocyanins, and PePE were found to mediate their protective effects through Nrf2 activation, while PoPE exerted multifaceted actions independent of Nrf2. Our results highlight the therapeutic potential of GrPE, PePE, and PoPE in shaping bacterial-host interactions, endorsing their utility as novel nutraceuticals for both oral and topical applications to prevent potential bacterial infections through i