Human Milk Oligosaccharide Supplementation Affects Intestinal Barrier Function and Microbial Composition in the Gastrointestinal Tract of Young Sprague Dawley Rats.

Faye Chleilat,Alana Schick,Raylene A Reimer,Kyle Ma,Teja Klancic,Jodi E Nettleton

doi:10.3390/nu12051532

Abstract

Human milk oligosaccharides (HMOs) are chief maternal milk constituents that feed the intestinal microbiota and drive maturation of the infant gut. Our objective was to determine whether supplementing individual HMOs to a weanling diet alters growth and gut health in rats. Healthy three-week-old Sprague Dawley rat pups were randomized to control, 2′-O-fucosyllactose (2′FL)- and 3′sialyllactose (3′SL)-fortified diets alone or in combination at physiological doses for eight weeks. Body composition, intestinal permeability, serum cytokines, fecal microbiota composition, and messenger RNA (mRNA) expression in the gastrointestinal tract were assessed. Males fed a control diet were 10% heavier and displayed elevated interleukin (IL-18) (p = 0.01) in serum compared to all HMO-fortified groups at week 11. No differences in body composition were detected between groups. In females, HMOs did not affect body weight but 2′FL + 3′SL significantly increased cecum weight. All female HMO-fortified groups displayed significant reductions in intestinal permeability compared to controls (p = 0.02). All HMO-fortified diets altered gut microbiota composition and mRNA expression in the gastrointestinal tract, albeit differently according to sex. Supplementation with a fraction of the HMOs found in breast milk has a complex sex-dependent risk/benefit profile. Further long-term investigation of gut microbial profiles and supplementation with other HMOs during early development is warranted.

Highlights

Breast milk consumption during the first year of life is a crucial determinant of gastrointestinal tract and microbiota development [1]
Newborns lack the enzymatic capacity to break down human milk oligosaccharides (HMOs) [10], these oligosaccharides are utilized by commensal gut bacteria and act as prebiotics wherein they serve as a growth factor that promotes a healthy gut microbiota, improving host health [11]
Our objective was to examine the effects of 20 fucosyllactose (20 FL) and 30 sialyllactose (30 SL) alone or in combination on growth and body composition, gut microbiota, intestinal permeability, and expression of genes involved in gut health in young female and male rats

Summary

Introduction

Breast milk consumption during the first year of life is a crucial determinant of gastrointestinal tract and microbiota development [1]. Breast milk can enhance the intestinal barrier and reduce chronic disease risk later in life [2]; infant formula is a commonly accepted alternative to breast milk. A prominent amount of the carbohydrates present include important complex structures known as human milk oligosaccharides (HMOs). Oligosaccharides in human milk belong to three major classes, i.e., neutral fucosylated, neutral non-fucosylated, and acidic [9]. Despite their physical characterization, the functional significance of the various HMOs is still not fully understood. Newborns lack the enzymatic capacity to break down HMOs [10], these oligosaccharides are utilized by commensal gut bacteria and act as prebiotics wherein they serve as a growth factor that promotes a healthy gut microbiota, improving host health [11]. HMOs were shown to affect microbe interactions in the host by serving as decoy receptors to prevent pathogen binding to intestinal epithelial cells [12]

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Results