Interspecies Systems Biology Uncovers Metabolites Affecting C. elegans Gene Expression and Life History Traits

• Published in: Cell 2014-02, Vol.156 (4), p.759-770
• Main Authors: Watson, Emma, MacNeil, Lesley T., Ritter, Ashlyn D., Yilmaz, L. Safak, Rosebrock, Adam P., Caudy, Amy A., Walhout, Albertha J.M.
• Format: Article
• Language: English
• Subjects: Animals; Betaproteobacteria - metabolism; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - growth & development; Caenorhabditis elegans - physiology; Comamonas; Diet; Escherichia coli; Escherichia coli - metabolism; Gene Expression Regulation; Metabolic Networks and Pathways; Methionine - metabolism; Molecular Sequence Data; Propionates - metabolism; S-Adenosylmethionine - metabolism; Transcriptome; Vitamin B 12 - metabolism
• ISSN: 0092-8674; 1097-4172
• 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. [Display omitted] •Interspecies systems biology paradigm links genetics to metabolites•Vitamin B12 is produced by the Comamonas, but not the E. coli, diet•Vitamin B12 affects development, fertility, and propionic acid toxicity•Vitamin B12 accelerates development via SAM metabolism An interspecies systems biology approach identifies vitamin B12, supplied by a diet of Comamonas bacteria, but not the standard E. coli diet, as a key micronutrient affecting C. elegans development and fertility.