Modulation of the Brain-Gut-Microbiota Axis in a Murine Model of Inflammatory Bowel Disease /

Anxiety, depression, and altered memory are increasingly being associated with intestinal diseases, including inflammatory bowel disease (IBD). Understanding the link between these behavioral changes and IBD may provide important clinical relevance since concomitant mood disorders often increase a patient's risk of requiring surgery and developing secondary functional gastrointestinal diseases (FGIDs). In the current study, anxiety-like behavior, as assessed by the light/dark box test, and non-spatial memory, as assessed by the novel object test, were determined at the peak and following the resolution of inflammation using the dextran sodium sulfate (DSS) mouse model of acute colitis. DSS was administered for 5 days via drinking water followed by either 3 or 9 days of normal drinking water for comparing behavior during active versus resolved inflammation, respectively. Mice were weighed throughout the study, colon lengths were measured at the time of sacrifice, and histological analysis was conducted in order to assess the degree of colonic disease. In addition, the composition of the gut microbiota was characterized using qPCR of DNA extracted from fecal pellets. Mice at 8 days post-DSS demonstrated impairments in non-spatial memory and anxiety -like behavior compared to controls. These behavioral defects did not persist following resolution of intestinal inflammation and were normalized by 14 days post-DSS. Furthermore, shifts in the composition of the gut microbiota were evident at the peak of intestinal inflammation - notably as decreases in lactobacilli and segmented filamentous bacteria (SFB) - which were also reversed by the time of resolution. Taken together, our findings support the hypothesis that in a murine model of IBD, changes in mood and behavior are present during acute inflammation in the presence of shifts in the composition of the gut microbiot