Animals are colonized by diverse bacterial strains that influence multiple aspects of the host's behavior and physiology. In particular, neuronal functions are now known to be modulated by the composition of an animal's microbiota. Enteric bacteria greatly influence behavior, mood, cognition, and the onset and progression of neurological diseases via modulation of neuron and neuronal circuit functions. However, it remains challenging to provide a mechanistic description of the effects of gut microbiota on nervous system function in the complex mammalian system. The nematode C. elegans is associated with a wide range of pathogenic and non-pathogenic bacteria in its natural habitat. C. elegans can be grown on monoxenic bacterial cultures, and hosts live bacterial colonies in its intestine. As in other animals, these gut bacteria have been shown to influence C. elegans physiology and health. We recently found that cultivation of C. elegans on non-pathogenic bacteria, and the presence of live gut bacteria, alter C. elegans chemosensory behaviors. The overall goal of this R21 is to take advantage of the experimental strengths of C. elegans to identify the molecular and neuronal mechanisms by which enteric bacteria influence sensory neuron function and sensory behaviors. The specific goals are to: 1) Analyze the neuronal mechanisms underlying gut microbe-induced behavioral plasticity. 2) Identify host molecular mechanisms that mediate gut bacteria-dependent changes in chemosensory behaviors. Innovative aspects of this work include the establishment of C. elegans as an experimental model for the study of the gut-brain axis, and analysis of the effects of enteric bacteria on sensory neuron and neural circuit function at high mechanistic resolution. Given the extensive conservation of many neuronal and physiological processes, insights from this work are expected to influence our understanding of the pathways by which commensal bacteria regulate diverse aspects of nervous system function in development and disease in other organisms.

Public Health Relevance

Animals host trillions of bacteria in their intestines. These bacteria influence and shape multiple aspects of host physiology and health, including metabolic rate, cognition, behavior, and the onset and progression of disease. In particular, gut bacteria communicate with the nervous system to alter neuronal functions and behaviors. We propose to establish the nematode C. elegans as a model system in which to examine the interactions between gut bacteria and the brain at high mechanistic resolution. Given the similarities in nervous system function across species, we expect that findings from this work will guide related research in other organisms, including in humans.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Exploratory/Developmental Grants (R21)
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Molecular Neurogenetics Study Section (MNG)
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Riddle, Robert D
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Brandeis University
Schools of Arts and Sciences
United States
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