A Gut Instinct: Engineering the Drosophila melanogaster Microbiome to Induce Behavioral Changes

Abstract

In humans, the composition and abundance of microbial species that reside inside the intestinal tract– termed the gut microbiome– plays an integral role in health. These microbes produce essential nutrients, modulate metabolic pathways, and promote immune system function [1, 2]. As such, gut microbiome dysbiosis– a disturbance from the homeostatic microbiome– is associated with various health complications, such as Irritable Bowel Syndrome, obesity, and Type-II Diabetes [3]. Beyond modulating physical health, the features of the gut microbiome also impact neurological activity and cognitive function via a bi-directional signaling pathway known as the gut-brain axis. Over the past decade, studies of this axis have revealed correlations between microbiome composition and the progression of neurodegenerative diseases such as Alzheimer’s and Parkinson’s, as well as mental illnesses such as anxiety and depression [4]. Here, we use the common fruit fly, Drosophila melanogaster, as a model organism for studying the gut-brain axis. With the aim of not only assessing the impact of the gut microbiome on stereotyped fly behaviors, but also exploring its effect on Drosophila circadian rhythms, we collect and analyze data over a 24-hour imaging window. We utilize high-resolution pose tracking and subsequent behavioral mapping to extract information regarding six stereotyped behaviors: locomotion, fore grooming, hind grooming, wing grooming, proboscis extension, and idle. From this data, we find that the daytime activity level and overall behavioral state of non-virgin female D. melanogaster is less sensitive to microbiome perturbations than that of non-virgin male Drosophila. Among male populations, we observe increased daytime activity levels following antibiotic treatment, which are rescued via monocolonization with Lactobacillus brevis and Lactobacillus plantarum. We also find that the circadian rhythms of female D. melanogaster are stabilized by the presence of a gut microbiome, as, upon microbiome removal, their night-day behavioral difference becomes more defined. This trend is not observed in male populations. Broadly, this project motivates the development and implementation of novel treatment methods for neurological disorders through high-resolution behavioral analysis of the Drosophila melanogaster gut-brain axis.