(OR14-05-24) Psychological Stress and Dietary Fiber Regulate Markers of Inflammation and Anxiety

Objectives: Prolonged stress exposure stimulates physiological release of pro-inflammatory molecules such as chemokine CCL-2 that initiate neuroinflammation, a contributor to psychopathological conditions including depression and anxiety. Prebiotic dietary fiber can ameliorate depressive-like behavior, suggesting it may be a promising therapeutic for neuroinflammation-driven psychopathological conditions. Therefore, the purpose of this study was to examine effects of psychological stress and prebiotic fiber supplementation on serum CCL-2 and anxiety- and depressive-like behavior.

Methods: Male and female C57BL/6 mice (age 6-8 weeks, n=6, N=96) were randomized into sixteen groups with factors of sex (male/female), two weeks of diet (1. Fiber-free diet [FFD] (base diet), 2. FFD + 20% cellulose [CELL] [non-prebiotic fiber control], 3. FFD + 10% cellulose + 10% short-chain fructooligosaccharide [scFOS] [short-chain prebiotic fiber], or 4. FFD + 10% cellulose + 10% inulin [INU] [long-chain prebiotic fiber]), and two hours of daily restraint stress exposure during the second week on diet (stressed [S] vs non-stressed [NS]). On day one of restraint, blood was collected at 0, 30, 60, 90, 120 min, and one hour post-stress (180 min) for quantification of CCL-2 via ELISA. Mice underwent open field and nest building tests to assess behavior. Spleen mass was collected as a marker of immune activation.

Results: Spleen mass was higher in females (p=0.01). Female CELL had lower spleen mass vs other diets (all p< 0.001). Male S-FFD had higher spleen mass vs NS-FFD (p=0.04). Total distance traveled in the open field was higher in females (p < 0.00001), and tended to be higher in S-FFD vs NS-FFD (p=0.06). S-males spent more time in the central zone (p=0.02). Nest building score was higher in S-FFD and S-scFOS vs other conditions (all p< 0.05). During the first bought of stress, CCL-2 was higher at 180 min in S-INU and S-scFOS vs S-FFD and S-CELL (all p < 0.05).<

Conclusions: Short-term dietary fiber intake regulates some markers of inflammation and affective disorders in a sex-dependent manner, likely via the gut-brain axis. CCL2 remains a potential target for the treatment of these diseases, but our results highlight the need to better understand its role in stress-induced conditions. Ongoing studies are examining makers of neuroinflammation in the central nervous system.

Funding Sources: UIUC