Defining Dysbiosis in Disorders of Movement and Motivation

Abstract

The gut microbiota has emerged as a critical player in shaping and modulating brain function and has been shown to influence numerous behaviors, including anxiety and depression-like behaviors, sociability, and cognition. However, the effects of the gut microbiota on specific disorders associated with thalamo-cortico-basal ganglia circuits, ranging from compulsive behavior and addiction to altered sensation and motor output, are only recently being explored. Wholesale depletion and alteration of gut microbial communities in rodent models of disorders, such as Parkinson's disease, autism, and addiction, robustly affect movement and motivated behavior. A new frontier therefore lies in identifying specific microbial alterations that affect these behaviors and understanding the underlying mechanisms of action. Comparing alterations in gut microbiota across multiple basal-ganglia associated disease states allows for identification of common mechanistic pathways that may interact with distinct environmental and genetic risk factors to produce disease-specific outcomes.

Keywords: Parkinson's; addiction; basal ganglia; compulsive behavior; gut microbiota; motor function.

Figure 1.

Gut microbial alterations occur within the context of genetic and environmental factors that shape basal ganglia-associated disease susceptibility. These host factors affect both gut microbial composition and basal ganglia function. Common microbial alterations associated with increased disease risk include increases in Proteobacteria, decreases in Prevotella, and alterations in Clostridia, which are all associated with increased gut barrier dysfunction. Other risk factors, such as altered short-chain fatty acid levels, increased vagal activation, and other mechanisms (e.g., the release of other bacterial metabolites) may also result from gut microbial alteration. Increased systemic inflammation and neuro-inflammation are common endpoints of all of these alterations, but other gut-to-brain mechanisms also contribute to basal ganglia disease etiology. Ultimately, gut-derived factors that alter basal ganglia function interact with other preexisting genetic and environmental susceptibility factors to shape specific disease outcomes.