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Human milk oligosaccharides and galactosyloligosaccharides attenuate inflammation in human intestine
Author(s) -
Newburg David,
Ko Jae,
Leone Serena,
Nanthakumar N Nanda
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.252.1
Subject(s) - inflammation , proinflammatory cytokine , immune system , immunology , colostrum , ex vivo , tumor necrosis factor alpha , intestinal mucosa , biology , receptor , in vivo , medicine , antibody , biochemistry , microbiology and biotechnology
The immature intestinal mucosa is hyperresponsive to exogenous and endogenous inflammatory insults. Human milk provides immune protection to infants, and its oligosaccharides (HMOS) are putative immunomodulators. Of these, galactosyloligosaccharides (GOS) are high in colostrum, but not mature milk. The objective is to determine the ability of GOS to directly attenuate inflammation, and potential mechanisms investigated. Human models of immature and mature intestine were used to investigate the ability of a mixture of HMOS or synthetic GOS to attenuate inflammation induced by proinflammatory stimuli and enteric pathogens. These results were confirmed in the ex vivo immature human intestinal organ cultures. The ability of TNFα and of pathogens to elicit pro‐inflammatory neutrophil chemoattractants IL‐8, MIP‐3α and MCP1 and their mRNA levels was significantly attenuated by HMOS and GOS. TNFα‐induced nuclear translocation of NF‐κB was mitigated by HMOS and GOS. Consistent with previous indications of bioactivity of galactosyllactose from human colostrum, trimeric galactosyloligosaccharides interact with cell receptors to inhibit inflammatory response. HMOS and GOS suppress NF‐κB activation, thereby directly attenuating TNFα‐ and pathogen‐induced inflammation in human intestine. This provides a novel mechanism whereby specific galactosyloligosaccharides found in human milk may prove a novel therapeutic agent against gut inflammation.