PT - JOURNAL ARTICLE AU - Michael P. O’Donnell AU - Bennett W. Fox AU - Pin-Hao Chao AU - Frank C. Schroeder AU - Piali Sengupta TI - Modulation of sensory behavior and food choice by an enteric bacteria-produced neurotransmitter AID - 10.1101/735845 DP - 2019 Jan 01 TA - bioRxiv PG - 735845 4099 - http://biorxiv.org/content/early/2019/08/15/735845.short 4100 - http://biorxiv.org/content/early/2019/08/15/735845.full AB - Animals coexist in commensal, pathogenic or mutualistic relationships with complex communities of diverse organisms including microbes1. Some bacteria produce bioactive neurotransmitters which have been proposed to modulate host nervous system activity and behaviors2. However, the mechanistic basis of this microbiota-brain modulation and its physiological relevance is largely unknown. Here we show that in C. elegans, the neuromodulator tyramine (TA) produced by gut-colonizing commensal Providencia bacteria can bypass the requirement for host TA biosynthesis to manipulate a host sensory decision. Bacterially-produced TA is likely converted to octopamine (OA) by the host tyramine beta-hydroxylase enzyme. OA, in turn, targets the OCTR-1 receptor on the ASH/ASI sensory neurons to modulate an aversive olfactory response. We identify genes required for TA 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 TA. 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.