Molecular Basis of Microbial Influence on Host Energy Balance

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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.