Evaluating the effect of prebiotic oligosaccharides on the infectious activity of enteric pathogens Salmonella Typhimurium and Listeria monocytogenes.

This project aimed to understand how different dietary prebiotic oligosaccharides influence interactions between gut pathogens and the intestinal epithelium. While prebiotics are widely used to support gut health, their effects on specific pathogens and host responses are not well defined. We focused on two structurally distinct prebiotics, human milk oligosaccharides (HMO) and mannanoligosaccharides (MOS), and their impact on two common foodborne pathogens, Salmonella enterica serovar Typhimurium and Listeria monocytogenes.The goal was to determine how these prebiotics alter pathogen behavior, host cell responses, and the overall infection outcome. We used human colonic epithelial cells (Caco-2) to assess changes in bacterial association, gene expression, and host signaling pathways.Both HMO and MOS reduced initial S. Typhimurium association with host cells, but triggered different downstream effects. HMO activated bacterial virulence islands linked to invasion, while MOS altered metabolism to resemble in vivo inflammatory conditions. For L. monocytogenes, HMO pretreatment reduced bacterial entry and activated stress pathways that promoted clearance, whereas MOS increased bacterial entry and induced autophagy, enabling bacterial survival.These findings are relevant for developing targeted dietary interventions. They demonstrate that not all prebiotics have protective effects. Some may unintentionally promote pathogen survival depending on context. A better understanding of these specific host-microbe-diet interactions is critical for designing safe and effective strategies to prevent or mitigate gut infections.

本研究旨在探究不同膳食益生元低聚糖如何影响肠道病原体与肠上皮细胞之间的相互作用。尽管益生元被广泛应用于维护肠道健康，但其针对特定病原体与宿主反应的作用机制仍未得到充分阐明。本研究聚焦于两种结构迥异的益生元：人乳低聚糖（human milk oligosaccharides, HMO）和甘露聚糖低聚糖（mannanoligosaccharides, MOS），以及它们对两种常见食源性病原体——肠炎沙门氏菌鼠伤寒血清型（Salmonella enterica serovar Typhimurium）和单核细胞增生李斯特菌（Listeria monocytogenes）的影响。本研究的目标是明确这些益生元如何改变病原体行为、宿主细胞应答及整体感染结局。我们采用人结肠上皮细胞（Caco-2）来评估细菌黏附、基因表达与宿主信号通路的变化。研究结果显示，HMO与MOS均能降低鼠伤寒沙门氏菌与宿主细胞的初始黏附水平，但二者触发的下游效应截然不同：HMO会激活与侵袭相关的细菌毒力岛，而MOS则使细菌代谢模式转向类似体内炎症环境的状态。针对单核细胞增生李斯特菌，HMO预处理可减少细菌入侵并激活促进病原体清除的应激通路；而MOS则会增加细菌入侵并诱导细胞自噬，进而助力细菌存活。上述研究结果可为开发靶向膳食干预手段提供参考依据。研究表明，并非所有益生元均具备保护作用，部分益生元在特定情境下可能会意外促进病原体存活。深入阐明这类宿主-微生物-膳食间的特异性相互作用，对于设计安全有效的肠道感染预防或缓解策略至关重要。