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

Abstract

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 in vitro 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 in vitro 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 in vitro epithelial wound repair assay. SL and GOS did show distinct modulation of microbiota composition, promoting the outgrowth of Bacteroides 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.

Human Milk Oligosaccharides Mediate the Crosstalk Between Intestinal Epithelial Caco-2 Cells and Lactobacillus Plantarum WCFS1in an In Vitro Model with Intestinal Peristaltic Shear Force

“…HMOs have been reported to contribute to the development of gut barrier function ( 4 ), mucus production ( 5 ), glycocalyx development ( 6 ), immune maturation ( 7 , 8 ), and shaping of the gut microbiota ( 9 , 10 ). However, many of these functions are identified in in vitro studies in intestinal cells under static culture, without the shear force that intestinal epithelium and other components of the gut immune barrier experience during peristalsis ( 11 ).…”

3′-Sialyllactose prebiotics prevents skin inflammation via regulatory T cell differentiation in atopic dermatitis mouse models

“…3′-SL acts as a prebiotic and leads to changes in the intestinal microbiota profiling. Some studies indicate that oral administration of 3′-SL increases the microbiota, including Bifidobacterium 34 . Especially, oral administration of these microbiota attenuated AD progression 35 .…”

“…3′-SL is known to promote the outgrowth of Bifidobacterium. Moreover, Bifidobacterium is a well-known probiotics for AD 34,35 . To check whether oral administration of 3′-SL modulates Bifidobacterium in normal conditions, we first determined levels of Bifidobacterium after administration of 3′-SL oral for 35 day in WT mouse.…”

Breastmilk Lipids and Oligosaccharides Influence Branched Short‐Chain Fatty Acid Concentrations in Infants with Excessive Weight Gain

“…HMOs influence infant growth possibly through microbiota modulation, energy harvest, and SCFA production; however, their effects are structure specific and may therefore depend on the HMO composition in the breastmilk. Multivariate analysis was able to pinpoint the strong direction in the pattern distinguishing HW‐ from NW‐infants, with a tendency to have lower concentrations of selected HMOs in the HW‐group, except for 2′FL.…”