A neuromodulator produced by commensalProvidenciabacteria that colonize the gut ofCaenorhabditis elegansmimics the functions of the cognate host molecule to manipulate a sensory decision of the host.
Animals coexist in commensal, pathogenic or mutualistic relationships with complex communities of diverse organisms, including microorganisms(1). Some bacteria produce bioactive neurotransmitters that have previously been proposed to modulate nervous system activity and behaviours of their hosts(2,3). However, the mechanistic basis of this microbiota-brain signalling and its physiological relevance are largely unknown. Here we show that inCaenorhabditis elegans, the neuromodulator tyramine produced by commensalProvidenciabacteria, which colonize the gut, bypasses the requirement for host tyramine biosynthesis and manipulates a host sensory decision. Bacterially produced tyramine is probably converted to octopamine by the host tyramine beta-hydroxylase enzyme. Octopamine, in turn, targets the OCTR-1 octopamine receptor on ASH nociceptive neurons to modulate an aversive olfactory response. We identify the genes that are required for tyramine biosynthesis inProvidencia, and show that these genes are necessary for the modulation of host behaviour. We further find thatC. eleganscolonized byProvidenciapreferentially select these bacteria in food choice assays, and that this selection bias requires bacterially produced tyramine and host octopamine signalling. Our results demonstrate that a neurotransmitter produced by gut bacteria mimics the functions of the cognate host molecule to override host control of a sensory decision, and thereby promotes fitness of both the host and the microorganism.
