Gut Microbiome Effects on Brain and Behavior

Microbes living in their host’s gut perform diverse functions related to nutrition, fighting disease, and behavior. In many cases, the gut microbiome performs necessary functions for its host, such that disruptions in the microbiome result in abnormalities. In other cases, the gut microbiome contributes to variation between individuals, such that differences in microbiomes between individuals drive differences in physiology and behavior.

However, it is not known whether gut microbiome function can change over the host’s lifetime. Furthermore, while various studies support the role of gut microbes in mediating host behavior, how they influence host behavior and the factors that mediate this interaction are largely unknown. This project addresses these important questions by studying how the gut microbiome influences behavioral maturation in the honey bee, Apis mellifera, which involves a transition in behavior from caring for larvae inside the hive and performing other in-hive tasks, to foraging for nectar and pollen outside of the hive.

This maturation process underlies age-related division of labor, so understanding the role of the gut microbiome in this process promises to illuminate our understanding of honey bee colony function. The results of these studies will also provide novel insights into the dynamics of host-microbe interactions, animal behavior and symbiosis, and gut-brain communication.

This project will provide integrative training in behavior, genomics, and microbiology to a diverse set of trainees at various career stages within the home institution, and will serve as the foundation for unique outreach and training activities for local K-12 students.

Understanding how the gut microbiome contributes to the functioning of the gut-brain axis is an emerging area of study in neuroscience, but the mechanisms supporting gut-brain communication remain poorly understood. To address this problem, this project will utilize state-of-the-art behavioral, genomic and genetic tools in the honey bee and its microbiome to determine the role that gut microbes play in honey bee behavioral maturation.

Specifically, this project will: 1) Use a combination of several honey bee colony-level manipulations, microbiome sequencing, and behavioral tracking to test the hypothesis that the microbiome influences behavioral maturation in the honey bee; 2) Perform single-microbe inoculations with microbes robustly associated with behavioral maturation, followed by metabolomic and transcriptomic analyses, in order to identify specific microbial factors that influence behavioral maturation and associate them with specific effects on host brain functioning and physiology; 3) Use a recently developed honey bee microbiome genetic toolkit to produce genetically modified microbes in order to functionally assess the role of specific microbial factors in behavioral maturation. Achieving these objectives will provide important new mechanistic insights into the gut-brain axis, and will determine whether and how the microbiome contributes to changes in behavior over the lifetime of an individual.

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.