RT Journal Article SR Electronic T1 Interplay between Mitochondria and Diet Mediates Pathogen and Stress Resistance in C. elegans JF bioRxiv FD Cold Spring Harbor Laboratory SP 154393 DO 10.1101/154393 A1 Alexey V. Revtovich A1 Ryan Lee A1 Natalia V. Kirienko YR 2017 UL http://biorxiv.org/content/early/2017/06/23/154393.abstract AB Diet is a crucial determinant of organismal biology. Here we demonstrate the dramatic impact of a subtle shift in diet on the ability of Caenorhabditis elegans to survive pathogenic or abiotic stress. Interestingly, this shift occurs independently of canonical host defense pathways, arising instead from improvements in mitochondrial health. Using a variety of assays, we reveal that the most common C. elegans food source (E. coli OP50) results in a vitamin B12 deficiency that compromises mitochondrial homeostasis. Increasing B12 supply by feeding on E. coli HT115 or by supplementing bacterial media with methylcobalamin restored mitochondrial function, even if the bacteria were dead. B12 supplementation also efficiently increased host health without adversely affecting lifespan. Our study forges a molecular link between a dietary deficiency (nutrition/microbiota) and a physiological consequence (host sensitivity), using the host-microbiota-diet framework. The ubiquity of B12 deficiency (~10-40% of US adults) highlights the importance of our findings.