Dynamic changes in gene expression is one strategy that animals can use to modify their behavior to dietary changes, but the molecular mechanisms underlying diet-dependent modulation of gene expression are unclear. We show here that the expression of the candidate
srh-234 chemoreceptor gene localized in a single ADL sensory neuron type of C. elegans is downregulated when animals are fed a Comamonas DA1877 bacterial diet relative to a low vitamin B12 diet of E. coli OP50 bacteria. This dietary effect of vitamin B12 on
srh-234 expression levels in ADL neurons is distinct from the starvation response we previously reported for
srh-234 regulation (Gruner, Grubbs et al, PLoS Genetics, 2014; and Gruner, Grubbs, McDonagh et al. PLoS Genetics, 2016). Remarkably, this diet-modulated effect on
srh-234 expression levels is dependent on vitamin B12 endogenously produced by Comamonas, because mutant strains of Comamonas bacteria that are deficient in vitamin B12 production fail to reduce expression levels of
srh-234 in ADL. Further analysis suggest that vitamin B12 likely does not act as an olfactory cue released by Comamonas bacteria, and does not depend on the modification or metabolism of E. coli bacteria to regulate
srh-234 expression. It is more likely that E. coli bacteria function as the vehicle for vitamin B12, because animals eating E. coli deficient in the tonB transporter shown to allow import of vitamin B12 from the extracellular environment suppress in part the vitamin B12-mediated reduction in
srh-234. Mutations in the C. elegans
mrp-5, a candidate vitamin B12 transporter, reduced but did not abolish
srh-234 expression in ADL in animals fed both E. coli and Comamonas, suggesting a yet unknown role for
mrp-5 in
srh-234 regulation. Propionate supplementation can bypass the repressing effects of vitamin B12 on
srh-234 regulation. Consistent with these findings, we found that mutations in
pcca-1 and
pccb-1 encoding for biosynthetic enzymes in the canonical propionate breakdown pathway suppressed, at least in part, the Comamonas-induced reduction in
srh-234 expression. We previously reported that the MEF-2 transcription factor acts together with bHLH factors to regulate the starvation-dependent modulation of
srh-234 expression. We found that mutations in
mef-2, but not in
hlh-30, are necessary for regulation of
srh-234 mediated by vitamin B12. Together, our findings suggest a MEF-2-dependent mechanism by which diet-supplied vitamin B12 transcriptionally tunes individual chemoreceptor genes in a single sensory neuron type, which in turn may change an animals' responses to biologically relative metabolites in their diet.