title: Interspecies systems biology uncovers metabolites affecting C. elegans gene expression and life history traits.
abstract: 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.
authors: 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.
authors: Emma
authors: E
authors: Watson
authors: 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.
authors: Lesley T
authors: LT
authors: MacNeil
authors: 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.
authors: Ashlyn D
authors: AD
authors: Ritter
authors: 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.
authors: L Safak
authors: LS
authors: Yilmaz
authors: 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.
authors: Adam P
authors: AP
authors: Rosebrock
authors: 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.
authors: Amy A
authors: AA
authors: Caudy
authors: 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. Electronic address: marian.walhout@umassmed.edu.
authors: Albertha J M
authors: AJ
authors: Walhout
mesh_terms: D000818:Animals; D020562:Betaproteobacteria / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D004032:Diet; D004926:Escherichia coli / Q000378:metabolism*; D005786:Gene Expression Regulation; D053858:Metabolic Networks and Pathways; D008715:Methionine / Q000378:metabolism; D008969:Molecular Sequence Data; D011422:Propionates / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D059467:Transcriptome; D014805:Vitamin B 12 / Q000378:metabolism
chemical_list: D011422:Propionates; D012436:S-Adenosylmethionine; D008715:Methionine; C029658:propionic acid; D014805:Vitamin B 12