噬菌体抑制刺参肠道中灿烂弧菌感染的作用机理研究

应用噬菌体替代抗生素进行动物细菌性疾病的防控研究已是当前热点。申请人前期研究表明饲喂噬菌体能够有效抑制刺参肠道中灿烂弧菌感染，宏基因组学分析结果明确了刺参肠道菌群失调与灿烂弧菌感染的相关性，但噬菌体在刺参肠道中的具体作用机理尚未明确。现有研究表明刺参肠道菌群可通过NF-κB信号通路影响刺参非特异免疫水平。本项目拟继续探究饲喂噬菌体后其在刺参肠道组织中的分布规律与时量关系；考察噬菌体对刺参肠道代表菌属丰度及代谢组的调节或恢复作用，分析肠道菌群及宿主共代谢产物；发掘噬菌体、肠道共代谢产物与NF-κB信号通路整体相关性并结合非特异免疫指标检测，最终提出“噬菌体-肠代谢-免疫轴”途径假说并加以验证，以揭示噬菌体抑制刺参肠道灿烂弧菌感染的作用机理。本项目研究结果可为噬菌体疗法在抗刺参感染领域的应用提供理论数据支撑，同时为进一步研究刺参肠道代谢与免疫互作机制奠定基础。

Using phage therapy strategy against bacterial infection as an alternative to antibiotics makes great interest now. Results of my previous work suggested the effectiveness of feeding phages in the control of V. splendidus infection in the intestinal tract of sea cucumber Apostichopus japonicus, and the correlation between the intestinal flora dysbacteriosis and Vibrio splendidus infection was confirmed by metagenomic analysis. Previous study has demonstrated intestinal microbiota could affect the non-specific immune response of sea cucumber through the NF-κB signaling pathway. Nevertheless, the specific action pathway of lytic phage against V. splendidus infection in the sea cucumber intestinal tract has not been clarified. To finally reveal the contributing factors of the effectiveness of phage application, in combination with the preliminary work foundation, this study intends to determine the distribution and time-concentration relationship of phage in the intestinal tract of sea cucumber after phage feeding treatment, investigate the regulation or protection of phage on the diversity of representative intestinal flora and metabolome, identify potential biomarkers by analyzing co-metabolites of intestinal flora and host. To explore whether there is a scientific relationship of the "phage-intestinal metabolism-immunity axis" in the intestinal tract of sea cucumber, supplemented with innate immune response, the communication pathway among phage, sea cucumber intestinal microorganism and metabolome, and NF-κB signal will be researched. Promising results in this work will provide theoretical data support for the phage therapy in the control of sea cucumber infection, as well as further research on the sea cucumber intestinal metabolism and immune interaction mechanism.