Milk oligosaccharides function as signalling molecules

Bethany Henrick, Foods for Health Institute and Dept. of Food Science and Technology,
University of California, Davis, USA

The intestinal mucosa is the body’s largest surface, and is among one of the most heavily glycosylated. It is thought that the principle function of these glycans is to mediate communicationwith the extra- cellular environment. Given that it is becoming increasingly clear that the microenvironment of this mucosal environment has a marked influence on the downstream immune responses, we need to better understand the interactions between ingested glycans, their effect on the intestinal microflora and, our primary focus, how they may serve as signalling molecules that directly impact intestinal epithelial and immune cells. Human milk oligosaccharides (HMO) are a family of structurally diverse (~200 species) unconjugated glycans that are highly abundant in (5-20 mg/mL), and have beneficial effects such as prebiotic effects, antiadhesive antimicrobial roles, and possibly have anti-inflammatory functions in both epithelial and immune cell. Similar in structure, unconjugated glycans known as bovine milk oligosaccharides (BMO) are also present in high concentration in bovine colostrum and may potentially exhibit similar modulating functions in epithelial and immune cells.

Importantly, BMOs represent an unlimited resource, and thus it is imperative to determine their immunomodulating effects on intestinal epithelial and immune cells. Using oligosaccharide fractions derived from human and bovine colostrum at the Milk Processing Lab, University of California, Davis, we first investigated the direct effects of HMO and BMO on the well-established intestinal epithelial cell (IEC) line, Caco-2. Our data showed that HMO induced an immediate and significant increase in COX-2 and tight junction protein, ZO-1 expression, and, interestingly, a significant but relatively mild production of pro- inflammatory cytokine, IL-8 in a dose-dependent manner. Detection of IL-8 production in the supernatant showed a significant but mild increase in Caco-2 supernatant. Likewise, supernatant tested from IEC lines exposed to BMO showed significantly increased IL-8 production.

We next tested the immunomodulating effects of both HMO and BMO, and observed that IECs treated with varying doses of HMO before LPS exposure showed a significant decrease in IL-8 production compared to medium alone. Conversely, IECs exposed to varying concentrations of BMO prior to LPS exposure produced significantly more proinflammatory cytokine compared to LPS alone. Taken together, these data suggest that milk oligosaccharides effect IEC signalling and should be investigated further for possible immunomodulatory therapies.

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