bstract # 3140 Gut microbial modulatory diets modulate stress-evoked sterile inflammation

Gut microbial modulatory (GMM) diets containing prebiotic nutrients favor the growth and metabolic function of health promoting gut bacteria and reduce the negative impacts of stressor exposure on mood, sleep, and gut microbial dysbiosis. Stressor exposure can increase inflammatory proteins in the absence of pathogens (sterile inflammation). This study tested the hypothesis that GMM diets modulate stress-evoked sterile inflammation. Male F344 rats were assigned either GMM diets or isocaloric-nutrient matched control diet. After 4 weeks, rats were exposed to stress (intermittent tailshock-90 min) or remained in their home cages. Immediately after stressor termination, rats were sacrificed and blood and tissues were collected. Consistent with previous results, GMM diets increased stress-protective gut bacteria (fecal L. rhamnosus ). Although GMM diet minimally impacted stress-induced increases in corticosterone, glucose or splenic contraction (indicative of sympathetic drive), it did constrain sterile inflammation, most notably CINC-1/CXCL8 (plasma, spleen, mesenteric lymph nodes (MLN)) and IL6 (plasma). GMM diets also increased IL10 (MLN) and reduced the stress-evoked increase in tissue Hsp72 (MLN, liver) compared to control, indicative of reduced cellular stress. The mechanisms for how GMM diets broadly impact stress physiology including sterile inflammation are unknown. Recent evidence, however, suggests that metabolic signals fueled by prebiotic nutrients from gut microbes impact the brain, increasing cfos in vagal afferent termination sites (NTS) and dorsal raphe nucleus (DRN); and prevent stress-evoked downregulation of DRN 5HT1AR.