Sialyllactose and Galactooligosaccharides Promote Epithelial Barrier Functioning and Distinctly Modulate Microbiota Composition and Short Chain Fatty Acid Production In Vitro

• Published in: Frontiers in immunology Vol. 10; p. 94
• Main Authors: Perdijk, Olaf, van Baarlen, Peter, Fernandez-Gutierrez, Marcela M, van den Brink, Erik, Schuren, Frank H J, Brugman, Sylvia, Savelkoul, Huub F J, Kleerebezem, Michiel, van Neerven, R J Joost
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 12-02-2019
• Subjects: Alkaline Phosphatase - metabolism; Bacteroides - growth & development; Bifidobacterium - growth & development; Caco-2 Cells; Celbiologie en Immunologie; Cell Biology and Immunology; Cell Cycle - genetics; Cell Differentiation; Cell Proliferation; epithelium; Fatty Acids, Volatile; galactooligosaccharides; Gastrointestinal Microbiome - physiology; Host Microbe Interactomics; Humans; Immunology; Infant; Intestinal Mucosa - pathology; Lactose - analogs & derivatives; Lactose - metabolism; Leerstoelgroep Celbiologie en immunologie; Leerstoelgroep Host Microbe Interactomics; microbiota; Milk, Human - metabolism; Oligosaccharides - metabolism; short chain fatty acids; Sialic Acids - metabolism; sialyllactose; Tight Junctions - pathology; Transcriptome; VLAG; WIAS; microbiota; galactooligosaccharides; epithelium; sialyllactose; short chain fatty acids
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2019.00094

Human milk oligosaccharides (HMO) and prebiotic oligosaccharides are proposed to confer several health benefits to the infant. They shape the microbiota, have anti-inflammatory properties, and support epithelial barrier functioning. However, in order to select the best oligosaccharides for inclusion in infant formulas, there is a need to increase our understanding of the specific effects of HMO and prebiotics on the host immune system. Therefore, we investigated the effects of the HMO sialyllactose (SL), and galactooligosaccharides (GOS) on epithelial barrier functioning, microbiota composition, and SCFA production. The effect of GOS and SL on epithelial barrier functioning and microbiota composition was investigated using
models. Epithelial barrier function was investigated by transcriptome analysis of fully polarized Caco-2 cells exposed for 6 h to SL or GOS. In addition, epithelial cell growth, alkaline phosphatase production, and re-epithelization was studied. Further, we investigated the effect of SL and GOS on microbiota composition and SCFA production using
fecal batch cultures. Transcriptome analysis showed that SL and GOS both induced pathways that regulate cell cycle control. This gene-expression profile translated to a phenotype of halted proliferation and included the induction of alkaline phosphatase activity, a marker of epithelial cell differentiation. SL and GOS also promoted re-epithelialization in an
epithelial wound repair assay. SL and GOS did show distinct modulation of microbiota composition, promoting the outgrowth of
and bifidobacteria, respectively, which resulted in distinct changes in SCFA production profiles. Our results show that SL and GOS can both modulate epithelial barrier function by inducing differentiation and epithelial wound repair, but differentially promote the growth of specific genera in the microbiota, which is associated with differential changes in SCFA profiles.