Program in Systems Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto M5S 3E1, Canada.
Cell. 2014 Feb 13;156(4):759-70. doi: 10.1016/j.cell.2014.01.047.
Diet greatly influences gene expression and physiology. In mammals, elucidating the effects and mechanisms of individual nutrients is challenging due to the complexity of both the animal and its diet. Here, we used an interspecies systems biology approach with Caenorhabditis elegans and two of its bacterial diets, Escherichia coli and Comamonas aquatica, to identify metabolites that affect the animal's gene expression and physiology. We identify vitamin B12 as the major dilutable metabolite provided by Comamonas aq. that regulates gene expression, accelerates development, and reduces fertility but does not affect lifespan. We find that vitamin B12 has a dual role in the animal: it affects development and fertility via the methionine/S-Adenosylmethionine (SAM) cycle and breaks down the short-chain fatty acid propionic acid, preventing its toxic buildup. Our interspecies systems biology approach provides a paradigm for understanding complex interactions between diet and physiology.
饮食对基因表达和生理学有很大影响。在哺乳动物中，由于动物及其饮食的复杂性，阐明单个营养素的作用和机制具有挑战性。在这里，我们使用秀丽隐杆线虫及其两种细菌饮食大肠杆菌和噬水气单胞菌的种间系统生物学方法，来鉴定影响动物基因表达和生理的代谢物。我们发现维生素 B12 是噬水气单胞菌提供的主要可稀释代谢物，它可以调节基因表达、加速发育、降低生育能力，但不影响寿命。我们发现维生素 B12 在动物中有双重作用：它通过蛋氨酸/S-腺苷甲硫氨酸（SAM）循环影响发育和生育能力，并分解短链脂肪酸丙酸，防止其有毒积聚。我们的种间系统生物学方法为理解饮食和生理学之间的复杂相互作用提供了范例。
