UC San Diego

Altered behavior and mood disorders, including anxiety, depression and cognitive dysfunction, are increasingly found to occur in the context of intestinal diseases such as inflammatory bowel disease (IBD) and negatively affect patient quality of life. The aim was to determine whether colonic inflammation precipitates behavioral deficits and whether these changes can be ameliorated by administration of probiotic organisms. Dextran sodium sulfate (DSS; 3% w/ v) was administered to 6-7 week old C57BL/6 mice via drinking water for 5 days followed by either 3 days (8 d post-DSS; height of disease) or 9 days (14 d post-DSS; resolution of disease) of normal drinking water. A subset of mice was given probiotics (Lactobacillus rhamnosus [R0011] and L. helveticus [R0052]; 10⁹ CFU/ml orally) starting 7 days prior to DSS and continuing until the end of the experiment. Changes in weight, colon length, behavior and microbiota were assessed. At 8 d post-DSS, weight loss and colonic shortening (both p<0.01) were observed, indicating colonic disease, and dysbiosis was also present. DSS mice (vs. controls) demonstrated impairments in recognition memory (p<0.01) and the presence of anxiety-like behavior (p<0.05), which were both resolved by 14 d post-DSS. Administration of probiotics ameliorated colonic disease (p<0.05), deficits in behavior (p<0.05 for cognition and anxiety-like behavior), and normalized levels of c-fos expression (p< 0.05) in the CA-1 region as well as partially restored the composition of the microbiota. Taken together, these findings indicate the presence of dysregulation of the microbiota-gut-brain axis in the setting of DSS-induced colitis that can be prevented by treatment with probiotics