Dietary xylooligosaccharide downregulates IFN-γ and the low-grade inflammatory cytokine IL-1β systemically in mice.

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 1 beta (II1 beta) (P < 0.01) and interferon gamma (Ifn gamma) (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 II1 beta (P < 0.01), Ifn gamma (P < 0.01), and interleukin 18 (II18) (P< 0.001) expression, supporting our hypothesis that increased production of short-chain fatty acids (SCFAs) in the gut, which are transported across the intestine and into the systemic compartments, results in downregulation of low-grade inflammatory cytokines. The defensin regenerating islet-derived protein 3 gamma (RegIII gamma) was significantly more highly expressed in the small intestine (P< 0.011 in XOS-fed mice compared with control-fed mice, suggesting only minor contact between bifidobacteria and epithelial cells. In support of this, the SCFA-induced sodium/hydrogen exchanger isoform 3 expression tended to be greater in the XOS group than in the control group (P= 0.06), indicating an indirect SCFA-mediated antiinflammatory effect of XOS. In conclusion, XOS feeding decreases systemic inflammation, and this effect is most likely caused by higher SOFA concentrations as a result of an increased bifidobacterial saccharolytic fermentation in the entire gut and not only in the large intestine. J. Nutr. 143: 533-540, 2013.