Protective Effects of Human Milk Oligosaccharides on Intestinal Epithelial Function Assessed in Enteroid‐Derived Monolayers

Abstract

Human milk oligosaccharides (HMOs) are structurally diverse carbohydrates that are unique to human milk and have beneficial effects on the growth and development of the intestine and immune system in breastfed infants. Infectious diarrheal diseases account for significant morbidity and mortality in young children and breastfeeding is protective against non‐typhoidal Salmonella infections and associated diarrhea in infants. Several studies suggest that HMOs may prevent enteric infections in breastfed infants and/or improve barrier function in transformed cell lines. Some of the beneficial effects of HMOs may be attributable to changes in the microbiota, but they likely have direct effects on the epithelium as well. The purpose of this study was therefore to evaluate mechanisms whereby HMOs may improve intestinal integrity and any protective effects of HMOs on Salmonella infection in a more clinically‐relevant model. We previously showed that Salmonella infection decreases epithelial barrier function in murine colon and in murine enteroid‐derived monolayers (EDM). In the present study, EDM were developed on permeable supports and, after differentiation, were exposed to pooled HMOs and then subsequently infected with Salmonella typhimurium at a multiplicity of infection of 10:1. Barrier integrity was determined by measuring transepithelial electrical resistance (TEER). We also measured bacterial internalization using a gentamicin protection assay followed by colony counts. Exposure of EDM to 10 mg/mL pooled HMOs for 2–8 h progressively increased TEER. Prior exposure to pooled HMOs prevented the decrease in TEER that was otherwise produced by Salmonella infection at 1 h after infection, but this effect was lost at later time‐points. Pooled HMOs had no effect on numbers of intracellular bacteria and did not alter bacterial growth when added to bacteria directly. Our results suggest that HMOs act directly on intestinal epithelial cells to strengthen intestinal barrier function both at baseline and when compromised by a pathogen. These effects may contribute to protection against the adverse outcomes of neonatal enteric infections.Support or Funding InformationLarsson Rosenquist Foundation Mother Milk Infant Center of Research ExcellenceThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.