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A neurotransmitter produced by gut bacteria modulates host sensory behaviour.

ABSTRACT: Animals coexist in commensal, pathogenic or mutualistic relationships with complex communities of diverse organisms, including microorganisms¹. 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 in Caenorhabditis elegans, the neuromodulator tyramine produced by commensal Providencia bacteria, 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 ?-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 in Providencia, and show that these genes are necessary for the modulation of host behaviour. 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 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.

SUBMITTER: O'Donnell MP

PROVIDER: S-EPMC7853625 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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A neurotransmitter produced by gut bacteria modulates host sensory behaviour.

O'Donnell Michael P MP Fox Bennett W BW Chao Pin-Hao PH Schroeder Frank C FC Sengupta Piali P

Nature 20200617 7816

Animals coexist in commensal, pathogenic or mutualistic relationships with complex communities of diverse organisms, including microorganisms<sup>1</sup>. Some bacteria produce bioactive neurotransmitters that have previously been proposed to modulate nervous system activity and behaviours of their hosts<sup>2,3</sup>. However, the mechanistic basis of this microbiota-brain signalling and its physiological relevance are largely unknown. Here we show that in Caenorhabditis elegans, the neuromodul ...[more]

PMID: 32555456

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Project description:Bacterial extracellular vesicles (BEVs) released from both Gram-negative and Gram-positive bacteria provide an effective means of communication and trafficking of cell signaling molecules. In the gastrointestinal tract (GIT) BEVs produced by members of the intestinal microbiota can impact host health by mediating microbe-host cell interactions. A major unresolved question, however, is what factors influence the composition of BEV proteins and whether the host influences protein packaging into BEVs and secretion into the GIT. To address this, we have analyzed the proteome of BEVs produced by the major human gut symbiont Bacteroides thetaiotaomicron both in vitro and in vivo in the murine GIT in order to identify proteins specifically enriched in BEVs produced in vivo. We identified 113 proteins enriched in BEVs produced in vivo, the majority (62/113) of which accumulated in BEVs in the absence of any changes in their expression by the parental cells. Among these selectively enriched proteins, we identified dipeptidyl peptidases and an asparaginase and confirmed their increased activity in BEVs produced in vivo. We also showed that intact BEVs are capable of degrading bile acids via a bile salt hydrolase. Collectively these findings provide additional evidence for the dynamic interplay of host-microbe interactions in the GIT and the existence of an active mechanism to drive and enrich a selected group of proteins for secretion into BEVs in the GIT. IMPORTANCE The gastrointestinal tract (GIT) harbors a complex community of microbes termed the microbiota that plays a role in maintaining the host's health and wellbeing. How this comes about and the nature of microbe-host cell interactions in the GIT is still unclear. Recently, nanosized vesicles naturally produced by bacterial constituents of the microbiota have been shown to influence responses of different host cells although the molecular basis and identity of vesicle-born bacterial proteins that mediate these interactions is unclear. We show here that bacterial extracellular vesicles (BEVs) produced by the human symbiont Bacteroides thetaiotaomicron in the GIT are enriched in a set of proteins and enzymes, including dipeptidyl peptidases, an asparaginase and a bile salt hydrolase that can influence host cell biosynthetic pathways. Our results provide new insights into the molecular basis of microbiota-host interactions that are central to maintaining GIT homeostasis and health.

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A neurotransmitter produced by gut bacteria modulates host sensory behaviour.

Publications

A neurotransmitter produced by gut bacteria modulates host sensory behaviour.

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