Molecular Basis of Microbial Influence on Host Energy Balance

描述(申请人提供)：人类已经进化出与肠道微生物(微生物区系)的亲密共生关系，这代表了我们获取和储存饮食卡路里的能力的功能延伸和影响。除了它在食物消化中的作用外，我预测微生物区系代表着一个“微生物器官”，它能产生类似激素的分子，影响能量平衡的内分泌调节。在这里，我建议使用线虫和一组不同的本地和人类肠道微生物来加速识别和表征宿主和微生物信号和调节宿主能量平衡的途径。线虫的遗传易操纵性、强大的细胞生物学工具、不变的解剖学、对高通量应用的适应性以及对微生物产品的生理调节使其成为解决这一问题的理想模型。事实上，线虫帮助阐明了脂肪储存和胰岛素信号传递的机制。在维持健康和治疗肥胖相关疾病方面，应考虑更广泛地认识微生物产品对发展能量失衡的贡献。

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.