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

Olaf Perdijk,R J Joost Van Neerven,Michiel Kleerebezem,Huub F J Savelkoul,Sylvia Brugman,Peter Van Baarlen,Frank H J Schuren,Marcela M Fernandez-Gutierrez,Erik Van Den Brink

doi:10.3389/fimmu.2019.00094

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.

Highlights

Microbial colonization directly after birth and breastfeeding are crucial events that determine health in neonatal and adult life [1, 2]
Since the majority of oligosaccharides are considered to be digested in the large intestine, undigested prebiotics may directly affect epithelial cells in the proximal regions of the intestinal tract
We performed a microarray to investigate what pathways were modulated by GOS or SL

Summary

Introduction

Microbial colonization directly after birth and breastfeeding are crucial events that determine health in neonatal and adult life [1, 2]. It has been widely recognized that breast milk confers health benefits to the infant by shaping the microbiota, preventing infections and promoting cognitive abilities [5]. Breast milk serves as the golden standard for infant nutrition and exclusive breastfeeding for the first 6 months in life is advocated by the WHO [6]. More than half of the infants is not exclusively breast-fed during the first 6 months of life worldwide [5] and is dependent on infant nutrition. Infant formulas are commonly supplemented with prebiotic oligosaccharides like galactooligosaccharides (GOS), fructooligosaccharides (lcFOS), or polydextrose, or a mixture of these. Among these polymeric glycans, GOS is the most widely used prebiotic oligosaccharide in infant nutrition

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