A neurotransmitter produced by gut bacteria modulates host sensory behaviour

Animals coexist in commensal, pathogenic or mutualistic relationships with complex communities of diverse organisms including microbes(1). Some bacteria produce bioactive neurotransmitters which have been proposed to modulate host nervous system activity and behaviors(2,3). However, the mechanistic basis of this microbiota-brain signaling and its physiological relevance is largely unknown. Here we show that in C. elegans, the neuromodulator tyramine produced by gut-colonizing commensal Providencia bacteria bypasses the requirement for host tyramine biosynthesis to manipulate a host sensory decision. Bacterially-produced tyramine is likely converted to octopamine by the host tyramine β-hydroxylase enzyme. Octopamine in turn targets the OCTR-1 octopamine receptor on the ASH nociceptive neurons to modulate an aversive olfactory response. We identify genes required for tyramine biosynthesis in Providencia, and show that these genes are necessary for modulation of host behavior. We further find that C. elegans colonized by Providencia preferentially select these bacteria in food choice assays, and that this selection bias requires bacterially produced tyramine and host octopamine signaling. Our results demonstrate that a neurotransmitter produced by gut microbiota mimics the functions of the cognate host molecule to override host control of a sensory decision, thereby promoting fitness of both host and microbe.