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Human milk exosomes dampen induced inflammatory response in human intestinal epithelial cells
Author(s) -
Kraft Jamie Dale,
Ferretti Emanuela,
Tremblay Eric,
Beaulieu JeanFrançois,
Altosaar Illimar
Publication year - 2018
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.2018.32.1_supplement.806.6
Subject(s) - microvesicles , immune system , human gastrointestinal tract , biology , gastrointestinal tract , immunology , in utero , intestinal epithelium , microbiology and biotechnology , fetus , epithelium , pregnancy , microrna , gene , biochemistry , genetics
After birth, upon exposure to the ex utero environment, the gastrointestinal tract of a newborn transitions from near sterile conditions to being exposed to a plethora of bacteria. In normal, term births the gastrointestinal tract matures through enteral feeds and commensal bacteria colonization. However, premature birth perturbs in utero organ maturation, thus depriving preterm infants of immune tolerance and increasing their susceptibility to gastrointestinal disorders. Human milk is the gold standard of infant nutrition, but in some cases, it is unavailable or insufficient. It is necessary to understand the components of human milk which facilitate development and promote immune tolerance to optimize feeding methods, ensuring best possible outcomes. Human milk exosomes have been shown to have immunomodulatory properties. Previous reports have demonstrated that milk exosomes survive in vivo digestion in animals, in vitro digestion in humans and can be taken up by human intestinal epithelial cells. We hypothesized that exosomes may promote immune tolerance in human intestinal epithelial cells. Exosomes were isolated from human milk through a series of centrifugations and ultracentrifugations. Post‐confluent Caco‐2/15 cells were incubated with either culture medium containing milk exosomes or PBS (control) for 24 hours. Caco‐2/15 cells, once maintained at post‐confluency, recapitulate mid‐gestation small intestine absorptive cells morphologically, functionally and at the gene level. An inflammatory response was induced by incubating the Caco‐2/15 cells with heat‐killed bacteria ( E. coli + S. typhimurium ). Expression of pro‐inflammatory markers, CXCL8, IL‐6 and CXCL10, was significantly decreased in cells pretreated with human milk exosomes compared to the control. Milk exosomes and their cargo caused a dampened immune response in human intestinal epithelial cells, suggesting that they may be promoting immune tolerance in the gastrointestinal tract of newborns. Infants born prematurely would benefit from such effects as their intestine is underdeveloped and more permeable, therefore, more susceptible to react to bacteria, causing an inflammatory cascade that could lead to sepsis. This is a relevant finding in identifying future directions to optimize feeding strategies for preterm infants. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .