RT Journal Article SR Electronic T1 Modulation of sensory behavior and food choice by an enteric bacteria-produced neurotransmitter JF bioRxiv FD Cold Spring Harbor Laboratory SP 735845 DO 10.1101/735845 A1 Michael P. O’Donnell A1 Bennett W. Fox A1 Pin-Hao Chao A1 Frank C. Schroeder A1 Piali Sengupta YR 2019 UL http://biorxiv.org/content/early/2019/08/15/735845.abstract 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.