益生菌Mycobacterium sp.延缓线虫衰老的分子机制研究

Diverse and abundant microbial communities resident in the human gut are tightly associated to the aging and health of their host. Due to the highly variability and diversity of gut microbiota community and physiological complexities of their mammalian hosts, our understandings on the underlying mechanisms of gut microbiota contributions on decelerating host aging are limited. Our previous studies found that 19 bacteria isolates from soil extended lifespan and induced stress and immune responses with C. elegans-bacteria model system. Isolate A33, belonging to genus Mycobacterium, prolonged lifespan over 40% compared to E. coli OP50 and attenuated the symptoms of neurodegeneration model in C. elegans. Thus, our researches are planning to investigate the contributions of A33 on the host physiological traits, including development, metabolism, health and aging. Moreover, to explore the underlying molecular mechanisms of the interplay between commensal A33 and their worm host aging, we are going to carry out genetic screen with both worm host and commensal A33, integrating transcriptome and metabolome profiling analysis, to identify and characterize the A33-derived metabolites contributing to host aging, and ensure signaling pathways response to commensal bacteria in C. elegans.

丰富多样的肠道微生物与机体健康和衰老息息相关。然而，由于肠道菌群结构复杂多变，且哺乳动物自身生理结构复杂、生长周期长，因此，对哺乳动物益生菌调控宿主衰老的机制还不清楚。本实验室利用秀丽线虫-细菌模式生物体系的优势，从土壤微生物库中筛选并鉴定出19株能够延长线虫寿命，并且参与压力和免疫应激的益生菌。其中，分支杆菌属的益生菌A33能延长线虫寿命达40%，并且延缓神经退行性疾病的进程。本项目拟进一步检测益生菌A33对宿主生理性状的影响，包括发育、代谢、以及延缓衰老。更重要的是，我们将利用宿主线虫与益生菌双向遗传筛选系统，结合转录组、代谢组学等分析手段，寻找并鉴定益生菌A33中延缓线虫衰老的有益代谢产物，以及线虫中参与调控长寿的信号通路，最终揭示益生菌A33延缓宿主衰老的分子机制。

丰富多样的肠道微生物与机体健康和衰老息息相关。然而，由于肠道菌群结构复杂多变，且哺乳动物自身生理结构复杂、生长周期长，因此，对哺乳动物益生菌调控宿主衰老的机制还不清楚。本实验室利用秀丽线虫-细菌模式生物体系的优势，从土壤微生物库中筛选并鉴定能够延长线虫寿命的益生菌A33，但是，对其参与调控宿主寿命的分子机制尚不清楚。本项目通过遗传通路分析、代谢组学检测等手段发现与长寿相关的DAF-16和SKN-1信号通路参与宿主响应A33的寿命调控。进一步，通过化学分离纯化的方法，分离纯化并鉴定出A33中调控宿主寿命的功能物质，包括多糖和肽聚糖，并发现其分别通过DAF-16和溶酶体信号通路调控线虫协同调控寿命。本研究为发掘了能够参与调控宿主寿命的多样的微生物资源，发现了新的细菌源的代谢物及其作用机制，帮助我们更深入的了解肠道菌与宿主相互作用的内在机制，同时为延缓衰老以及治疗衰老相关的疾病，提供新的策略和手段。