Collaborative Research: Modulation of pheromone-dependent host behavior by gut bacteria

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Animals live in association with many microorganisms including bacteria, collectively referred to as their microbiota. Microbiota are now well known to regulate development and behaviors of animals. However, how bacteria, present for example in the gut, influence animal development and disease is poorly understood. The nematode C. elegans, a tiny worm, is a well-studied experimental organism that consumes bacteria. Some bacteria survive and colonize the worm gut, where they produce chemicals that influence worm physiology and behavior. Preliminary results indicate that specific bacterial diets can change social and food-finding behaviors of these worms. This project explores how chemicals made by the bacteria target the worm’s nervous system to alter its behaviors. The studies will identify the bacterial chemicals and genes required for production of the chemicals and determine how manipulating these genes in the bacteria affect the worm’s nervous system. Together, this research provides a detailed description of how interactions among different organisms, specifically animals and associated microbiota, shape their life cycles. The research program supports the research experiences of high school, undergraduate and graduate students, and postdoctoral fellows with efforts made to recruit and involve members of underrepresented minority groups in this work. Results and foundational scientific principles will be shared with the public via hands-on demonstrations at local science museums, via public presentations, and by the involvement of project participants in local outreach activities. This work incorporates a collaboration between neuroscientists and chemists, and promotes interdisciplinary training in this way.Microbiota are now well-established to play critical roles in modulating host physiology and behavior. The mechanisms by which bacterial metabolites regulate host neuronal functions to influence behavioral outputs is unclear. The nematode C. elegans consumes bacteria and is associated with diverse bacterial species in the wild. A subset of commensal bacteria can survive and colonize the worm gut. Preliminary work indicates that growth of C. elegans on specific bacterial strains alters its exploratory behavior, in part via the regulation of production of specific pheromones. The project combines the complementary expertise of the Sengupta lab in C. elegans behavioral analysis and the Schroeder lab in metabolomics to describe the mechanisms by which the interaction of C. elegans with specific bacterial strains alters the host’s nervous system functions. Specifically, the work characterizes bacteria-driven behavioral modulation, identifies the targeted neurons in C. elegans, and characterizes the mechanisms by which bacterial metabolites alter neuronal properties. This research uses bacterial and C. elegans genetics, as well as unbiased metabolomics, to identify and manipulate bacterial and nematode biochemical pathways, and characterize the effects of these manipulations on host behavior. Results from this collaborative and interdisciplinary work will provide new insights into the mechanisms by which animal behavior is regulated in response to specific organismal interactions. In particular, the project will provide insights into how animals leverage their microbiota to alter metabolic pathways, thereby coupling their environmental experiences with behavioral plasticity.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.