‘Mind-altering bugs’: Dissecting the gut-microbiome-brain connection using a multidisciplinary approach in Drosophila melanogaster

Abstract

Why is the tragedy of autism increasing in Western societies? Some suggest that this is the result of better diagnosis, while others maintain that changing environmental factors interacting with multiple human genes are contributing to the increase. This makes autism very hard to treat, and even harder to cure. Recent scientific breakthroughs suggest that combined with a genetic element, this disease may be triggered and worsened by disruptions in the normal bacterial community that resides in the human gut - the human microbiome. In other words, healthy microbial communities are being replaced with nasty ones (unsavory elements move into the neighborhood). Such changes in gut biology are not only associated with autism, but also with other pediatric and adult diseases including obesity, inflammatory bowel disease, and susceptibility to bacterial infections. Why the incidence of these diseases is increasing in society is unclear, but it may be the result of excessive antibiotics used to treat childhood illnesses, dietary changes that harm our gut microbes, or both. To understand how human microbial communities influence human health and disease, we are developing a robust, affordable, and rapid model to specifically study the effect of gut microbes on animal behavior. We refer to this as the “gut-microbiome-brain connection”. Much of what we know about the way we fight harmful microbes has been discovered in the fruit fly, Drosophila. We plan to combine this fly host model with state-of-the art genomics and proteomics technologies to associate gut microbes with host protein expression, gut cell function, and behavior. Our short-term goal is to discover previously unknown mechanisms connecting microbes to host cells, and determine how these changes affect host physiology and behavior. Our long-term goal is to use this basic research to help us understand how our microbes contribute to human behavior, and how microbes can be used to prevent and treat debilitating human behavioral disorders.

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