Human milk oligosaccharides attenuate bacterial endotoxin-induced fever in mice.

Abstract

AIMS: Human milk oligosaccharides (HMOs) are biologically active substances that may play a protective role against infections in newborns. We investigated the effects of HMOs in vivo on endotoxin-induced fever in a murine model of systemic inflammation resembling Gram-negative infection. MAIN METHODS: Mice were administered intraperitoneally (i.p.) with HMOs (2'-FL, 3'-FL, 3'-SL, 6'-SL, LNT, LNnT) at equimolar doses (0.02&#xa0;mmol/kg) 0, 2 or 4&#xa0;h before or 1&#xa0;h after fever induction with a single dose of bacterial lipopolysaccharide (LPS; 120&#xa0;&#x3bc;g/kg&#xa0;i.p.). 2'-FL was also administered intragastrically 2&#xa0;h before LPS treatment. Core temperature of the animals was recorded throughout the experiments. In separate experiments, plasma and tissue (liver, lung, and brain) samples were collected for LC-MS and PCR analysis, respectively. KEY FINDINGS: Saline-pretreated animals developed fever after LPS administration, peaking at 38.7&#xa0;&#xb1;&#xa0;0.6&#xb0;C (p&#xa0;<&#xa0;0.05). However, pretreatment with 2'-FL and LNT 2&#xa0;h before LPS significantly (p&#xa0;<&#xa0;0.001) reduced the fever response compared to saline pretreatment with maximum values of 37.5&#xa0;&#xb1;&#xa0;0.4 and 37.6&#xa0;&#xb1;&#xa0;0.3&#xb0;C, respectively. In case of 2'-FL, a protective effect was also demonstrated when given together with LPS or 4&#xa0;h before i.p. (p&#xa0;<&#xa0;0.05), as well as when given orally or to newborns. The LPS-induced upregulation of cyclooxygenase-2 was not affected by 2'-FL pretreatment. SIGNIFICANCE: The studied HMOs had no effect on body temperature per se, but pretreatment with two of them (2'-FL, LNT) attenuated the LPS-induced fever response. Our results confirm that breastfeeding is of paramount importance against bacterial infections, in which the protective effect of HMOs is crucial.