Modulation of the microbiota-gut-brain axis by probiotics in a murine model of inflammatory bowel disease

摘要

Anxiety, depression, and altered memory are associated with intestinal diseases, including inflammatory bowel disease (IBD). Understanding the link between these behavioral changes and IBD is important clinically since concomitant mood disorders often increase a patient's risk of requiring surgery and developing secondary functional gastrointestinal diseases. Anxiety-like behavior (light/dark box test) and recognition memory (novel object recognition task) were determined at the peak and during resolution of inflammation in the dextran sodium sulfate (DSS) mouse model of acute colitis. DSS (5 days) was administered via drinking water followed by 3 or 9 days of normal drinking water to assess behavior during active or resolving inflammation, respectively. Disease (weight, colon length, and histology) was assessed and the composition of the gut microbiota was characterized by using qPCR on fecal pellet DNA. In a subset of mice, pretreatment with probiotics was started 1 wk prior to commencing DSS. During active inflammation (8 days), mice demonstrated impaired recognition memory and exhibited anxiety-like behavior vs. controls. These behavioral defects were normalized by 14 days post-DSS. Shifts in the composition of the gut microbiota were evident during active inflammation, notably as decreases in lactobacilli and segmented filamentous bacteria, which were also reversed once the disease had resolved. Administration of probiotics could prevent the behavioral defects seen in acute DSS. Taken together, our findings indicate that changes in mood and behavior are present during acute inflammation in murine IBD and associated with dysbiosis and that these outcomes can be prevented by the administration of probiotics.