Michael O'Donnell, PhD
Postdoctoral Research Fellow
Sengupta Lab
Brandeis University
(September 27, 2019)
Modulation of sensory behavior and food choice by an enteric bacteria-produced neurotransmitter
A healthy gut microbiome has become a trendy catchphrase in the world of personal health these days. But do these bacteria really play a functional role? In worms they do. Dr. O’Donnell discussed his research with the model organism C. elegans and the bacteria found naturally in the gut of this species. The bacteria create a chemical signall that affects smell and feeding behavior. This work begins to shed light on the true effects of naturally occurring gut bacteria.
For over 50 years it has been known that single-celled organisms such as bacteria are capable of producing chemicals that closely resemble the signals used by animal nervous systems, called neurotransmitters and neuromodulators. These discoveries led to a fundamental question: do microbes use these neurotransmitters to alter the behavior of their animal hosts? While examples of animal behavioral changes induced by microbes have been found in mammals, no clear examples have been identified showing a direct effect of bacterial neurotransmitters on neurons in the brain to elicit these changes. Using the small roundworm, C. elegans, we have discovered that natural gut bacteria can produce the neurotransmitter tyramine, and that the production of this chemical alters feeding behaviors and response to odors by the worm.
We have found that members of the Providencia genus of Gram-negative bacteria encode enzymes for the production of tyramine, and using genetic tools, we have shown that bacterial tyramine production is essential for the worm's behavioral changes. These bacteria are found in association with C. elegans in the wild, and efficiently colonize the intestine and produce tyramine in the lab. This bacterially-derived tyramine accumulates in the worm, and remarkably, can even functionally replace the levels of tyramine when host biosynthesis is blocked. Bacterially-derived tyramine is then converted by the host to a second neurotransmitter, octopamine. In invertebrates, tyramine and octopamine together are analogous to the catecholamines of the vertebrate adrenergic system, epinephrine and norepinephrine. Octopamine derived from Providencia-produced tyramine then signals to an olfactory neuron via a G-protein-coupled receptor called OCTR-1, reducing responses to aversive odors. This production of tyramine also results in increased feeding preference toward these Providencia bacteria, which is likely advantageous for both host and microbe.There is growing evidence that natural products from microbes can have profound physiological effects on animal hosts. In some cases these metabolites can functionally replace those of the host and may be incorporated into novel biosynthetic pathways, as we have shown here. These results suggest that emerging host models such as C. elegans can be valuable tools to gain mechanistic insights into how the dynamics of interspecies chemical communication shapes host-microbe associations and nervous system function.