Abstract P331: Diet and Probiotic Administration Significantly Influence Behavior and Forebrain Inflammation in Male Mice

Abstract

There is a high degree of comorbidity between psychological and gastrointestinal disease, which implies a functional relationship exists between the two systems. Collectively, research suggests that the gut-brain axis is bidirectional, and involves complex relationships between immune, neural, endocrine, and metabolic pathways. In this pilot study, we seek to further investigate the microbiome’s role in a bottom-up model by studying the short-term effects of different diets and probiotic supplementation on behavior and the expression of inflammatory biomarkers in the forebrain. Weanling, male C57Bl/6 mice were purchased from a commercial vendor and acclimated to a solid diet for one-week. Mice were randomly assigned to receive one of three diets for eight weeks: chow, the American Institute of Nutrition 1993 formulation (AIN), or our novel Americanized diet (AD). After six-weeks of diet, mice were then administered a commercially available probiotic, or water control, for the final two weeks of the study. Aggressive tendencies were measured during the probiotic administration period and dietary intake was recorded during the final week of the study. Animals were then euthanized and the forebrain was dissected and processed for the quantification of mRNA for Bdnf (BDNF), Nfkb1 (Nf-κb), Gfap (GFAP), Ptgs2 (PTGS2), and Nr3c1 (NR3C1) by real-time RT-PCR. Data were analyzed using General Linear Model Procedures in SPSS with significance determined at P<0.05. There was a significant decline (P<0.001) in aggressive behavior over the testing period, and mice administered the probiotic tended (P=0.15) to display less signs of aggression regardless of the diet. For dietary intake, there was a numerical increase in daily caloric intake in mice consuming the AD (~13 kcal/day), while mice consuming chow and AIN were similar (9 and 10 kcal/day, respectively). Additionally, there were numerical differences between probiotic and control groups for two of the diets. Quantification of gene expression in the forebrain revealed that diet significantly (P=0.002) affected GFAP expression, with mice consuming chow having significantly lower values than mice fed AIN or AD. Probiotic treatment significantly (P=0.02) affected NF-κB expression, with mice administered the probiotic having greater forebrain NF-kb as compared to control mice. This was most obvious in mice fed the chow and AIN diets, but not the AD. Collectively, our pilot study’s findings suggest that short term probiotic supplementation and dietary variation have potential effects on neuroinflammation, brain function, and satiety. Furthermore, our data indicates that the efficacy of probiotic administration is dependent upon the quality of diet consumed.