Gut Barrier Dysfunction and Type 2 Immunity: Implications for Compulsive Behavior

To date, much of the focus of gut-brain axis research has been on gut microbiota regulation of anxiety and stress-related behaviors. Much less attention has been directed to potential connections between gut microbiota and compulsive behavior. Here, we discuss a potential link between gut barrier dysfunction and compulsive behavior that is mediated through "type 2" rather than "type 1" inflammation. We examine connections between compulsive behavior and type 2 inflammation in Tourette syndrome, obsessive-compulsive disorder, autism, addiction, and post-traumatic stress disorder. Next, we discuss potential connections between gut barrier dysfunction, type 2 inflammation, and compulsive behavior. We posit a potential mechanism whereby gut barrier dysfunction-associated type 2 inflammation may drive compulsive behavior through histamine regulation of dopamine neurotransmission. Finally, we discuss the possibility of exploiting the greater accessibility of the gut relative to the brain in identifying targets to treat compulsive behavior disorders.