The principal fucosylated oligosaccharides of human milk exhibit prebiotic properties on cultured infant microbiota

Abstract

Breast-fed infant microbiota is typically rich in bifidobacteria. Herein, major human milk oligosaccharides (HMOS) are assessed for their ability to promote the growth of bifidobacteria and to acidify their environment, key features of prebiotics. During in vitro anaerobic fermentation of infant microbiota, supplementation by HMOS significantly decreased the pH even greater than supplementation by fructooligosaccharide (FOS), a prebiotic positive control. HMOS elevated lactate concentrations, increased the proportion of Bifidobacterium spp. in culture, and through their fermentation into organic acids, decreased the proportion of Escherichia and Clostridium perfringens. Three principal components of HMOS, 2'-fucosyllactose, lactodifucotetraose and 3-fucosyllactose, were consumed in these cultures. These three principal oligosaccharides of human milk were then individually tested as supplements for in vitro growth of four individual representative strains of infant gut microbes. Bifidobacterium longum JCM7007 and B. longum ATCC15697 efficiently consumed oligosaccharides and produced abundant lactate and short-chain fatty acids, resulting in significant pH reduction. The specificity of fermentation differed by microbe species and strain and by oligosaccharide structure. Escherichia coli K12 and C. perfringens did not utilize appreciable fucosylated oligosaccharides, and a typical mixture of organic acid fermentation products inhibited their growth. In summary, 2'-fucosyllactose, lactodifucotetraose, and 3-fucosyllactose, when cultured with B. longum JCM7007 and B. longum ATCC15697, exhibit key characteristics of a prebiotic in vitro. If these bifidobacteria are representative of pioneering or keystone species for human microbiota, fucosylated HMOS could strongly promote colonization and maintenance of a mutualist symbiotic microbiome. Thus, these simple glycans could mediate beneficial effects of human milk on infant health.

The Human Milk Oligosaccharide 2′-Fucosyllactose Quenches Campylobacter jejuni–Induced Inflammation in Human Epithelial Cells HEp-2 and HT-29 and in Mouse Intestinal Mucosa

“…Prebiotics, indigestible dietary glycans that confer health benefits, increase diversity and numbers of intestinal microbiota. HMOSs, which are prebiotics, promote the colonization of the distal gut by mutualistic bacteria that selectively ferment HMOSs to produce organic acids, reduce ambient pH, and inhibit growth virulence of pathogens (40). Such changes would reduce C. jejuni infection and mucosal inflammatory responses.…”

Human milk and infant intestinal mucosal glycans guide succession of the neonatal intestinal microbiota

“…E. coli K12 and C. perfringens, which are not mutualists, did not utilize appreciable fucosylated oligosaccharide. Moreover, a typical mixture of organic acid fermentation product produced by the mutualists inhibited the growth of these nonmutualists (33). Thus, HMOS and their major fucosylated components are prebiotic to the mutualists and the mutualist fermentation products inhibit pathogens and opportunists.…”

“…The glycans expressed on the surface of the infant intestinal mucosa have been demonstrated to select for distinct bacteria; specifically, the fucosylated glycans of secretors select for microbes that utilize fucose (31). This is complemented by the prebiotic effect of the dominant fucosylated oligosaccharides of human milk, which are prebiotic, and specifically stimulate the growth of bifidobacteria and bacteriodes, predominant mutualists in healthy microbiota (32,33).…”

Human Gut Microbiota and Obesity During Development

“…possess gene clusters dedicated to the metabolism of HMOs [73,74]. Degradation of these compounds produces lactate and short-chain faty acids (SCFA), which in turn generates an acidic environment that prevents pathogen invasion [75]. Besides Biidobacteria, HMOs may be consumed by other species such as Bacteroides spp.…”