Vitamin B12 produced by gut bacteria modulates excitatory neurotransmission

A growing body of evidence indicates that gut microbiota influence brain function and behavior. However, the molecular basis of how gut bacteria modulate host nervous system function is largely unknown. Here we show that vitamin B12-producing bacteria that colonize the intestine can modulate excitatory synaptic transmission and behavior in the host Caenorhabditis elegans. We find that vitamin B12 reduces cholinergic signaling in the nervous system through rewiring of the methionine (Met)/S-Adenosylmethionine (SAM) cycle in the intestine. We identify a conserved metabolic crosstalk between the Met/SAM cycle and the choline oxidation pathway. We show that metabolic rewiring of these pathways by vitamin B12 reduces cholinergic transmission by limiting the availability of free choline required by neurons to synthesize acetylcholine. Our study reveals a gut-brain communication pathway by which enteric bacteria modulate host behavior and may affect mental health.