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Dietary carbohydrates improve growth conditions for distinct populations of bacteria that may affect mucosal and systemic immunity. In this study, we fed in a parallel experiment a 10% xylooligosaccharide (XOS)–supplemented diet or a control diet to 2 groups of male C57BL/6NTac mice for 10 wk from weaning. We found that the XOS diet significantly increased Bifidobacterium throughout the intestine compared with control-fed mice, with the highest proportions found in the ileum after XOS feeding (P < 0.001). In the intestinal epithelium, most innate immune-related genes were unaffected by XOS feeding, whereas expression of interleukin 1β (Il1β) (P < 0.01) and interferon γ (Ifnγ) (P < 0.05) was significantly less in blood from XOS-fed mice than from control-fed mice. In vitro treatment of blood with propionate significantly decreased Il1β (P < 0.01), Ifnγ (P < 0.01), and interleukin 18 (Il18) (P < 0.001) expression …