Molecular Basis of Microbial Influence on Host Energy Balance

描述（由申请人提供）：人类已经进化出与肠道微生物（微生物群）联盟的亲密共生关系，这些微生物代表了我们获取和储存膳食卡路里的能力的功能延伸和影响。除了在食物消化中的作用外，我预测微生物群代表了一种“微生物器官”，它会产生影响能量平衡的内分泌调节的类酵母分子。这里我建议使用C。elegans和一组不同的天然和人类肠道微生物，以加快宿主和微生物信号和调节宿主能量平衡的途径的鉴定和表征。C.线虫的遗传易处理性、稳健的细胞生物学工具、不变的解剖结构、对高通量应用的适应性和对微生物产物的生理调节使其成为解决该问题的理想模型。的确，C. elegans帮助阐明了脂肪储存和胰岛素信号传导的机制。在保持健康和治疗肥胖相关疾病时，应考虑更广泛地了解微生物产品对能量失衡发展的贡献。

DESCRIPTION (provided by applicant): Humans have evolved intimate symbiotic relationships with a consortium of gut microbes (microbiota) that represent a functional extension of and influence upon our ability to acquire and store dietary calories. Beyond its role in digestion of food, I predict that the microbiota represents a 'microbial organ' that produces hormone-like molecules that affect endocrine regulation of energy balance. Here I propose to use C. elegans and a diverse panel of native and human gut microbes to expedite the identification and characterization of the host and microbial signals and pathways that modulate host energy balance. C. elegans' genetic tractability, robust cell biological tools, invariant anatomy, amenability to high-throughput applications and physiologic tuning to microbial products make it an ideal model to address this question. Indeed, C. elegans has helped elucidate the mechanisms of fat storage and insulin signaling. A broader appreciation of the contribution of microbial products to development of energy imbalances should be considered in maintaining good health and treatment of obesity-related disorders.