Dietary Xylooligosaccharide Downregulates IFN-gamma and the Low-Grade Inflammatory Cytokine IL-1 beta Systemically in Mice

Camilla H. F. Hansen,1* Hanne Frøkiær,1 Annette G. Christensen,1 Anders Bergström,2 Tine R. Licht,2 Axel K. Hansen,1 and Stine B. Metzdorff1

1Section of Biomedicine, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark; and 2National Food Institute, Division of Microbiology and Risk Assessment, Technical University of Denmark, Søborg, Denmark


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 1b (Il1b) (P < 0.01) and interferon g (Ifng) (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 Il1b (P < 0.01), Ifng (P < 0.01), and interleukin 18 (Il18) (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 3g (RegIIIg) was significantly more highly expressed in the small intestine (P < 0.01) 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 SCFA concentrations as a result of an increased bifidobacterial saccharolytic fermentation in the entire gut and not only in the large intestine.

J. Nutr. doi: 10.3945/jn.112.172361.

Journal of Nutrition
24 JULY 2024