Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE). Universidad Miguel Hernández de Elche, 03202 Alicante, Spain; Instituto Universitario de Ingeniería de Alimentos-FoodUPV, Universitat Politècnica de València, 46022 Valencia, Spain.
Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE). Universidad Miguel Hernández de Elche, 03202 Alicante, Spain.
Phytomedicine. 2024 Nov;134:156020. doi: 10.1016/j.phymed.2024.156020. Epub 2024 Sep 2.
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 innovative mechanisms.
肠道和皮肤上皮在抵御细菌刺激方面发挥着重要作用，但当刺激超过承受能力时，会引发炎症和氧化应激。富含水果的饮食和副产品中的多酚具有抵抗细菌有害影响的潜力，但它们的抗菌和促进健康的作用仍有待研究。
本研究旨在评估葡萄（GrPE）、柿子（PePE）和石榴（PoPE）副产物的多酚提取物对细菌病原体-宿主相互作用的影响，重点研究其抑制生长以外的作用，探索其对细菌黏附、入侵和宿主反应调节的影响。
采用微量稀释法和基于四唑的 MTT 细胞增殖和细胞毒性测定法，结合结晶紫染色，确定抑制细菌黏附、入侵或脂多糖（LPS）对宿主细胞作用而不损害宿主细胞活力的提取物亚抑制浓度。在核因子红细胞 2 相关因子 2（Nrf2）敲低模型中评估提取物的细胞保护作用。
所有提取物均显著降低了病原体对 Caco-2 和 HaCaT 细胞的黏附，同时保持了细胞完整性。值得注意的是，PePE 对沙门氏菌的黏附具有特异性作用，这主要归因于其没食子酸含量，而 PoPE 则降低了 Caco-2 细胞中沙门氏菌的入侵。提取物支持肠道和皮肤表面的非致病性和共生菌株的流行，选择性地减少了致病性菌株的黏附。提取物减轻了氧化应激，增强了屏障功能，并调节了 LPS 刺激细胞中的促炎细胞因子。富含花青素的 GrPE 和 PePE 被发现通过 Nrf2 激活介导其保护作用，而 PoPE 则通过与 Nrf2 无关的多方面作用发挥作用。
我们的研究结果突出了 GrPE、PePE 和 PoPE 在调节细菌-宿主相互作用方面的治疗潜力，支持它们作为新型营养保健品用于口服和局部应用，通过创新机制预防潜在的细菌感染。
