Utilization of major fucosylated and sialylated human milk oligosaccharides by isolated human gut microbes

Abstract

Human milk oligosaccharides (HMOS) are not digested in the proximal intestine. In distal intestine, HMOS collectively modify the microbiota, but the response of individual bacteria to individual components of the HMOS is not well defined. Here, each of 25 major isolates of the human intestinal microbiota was fed individual major fucosylated and sialylated HMOS in anaerobic culture. This allowed for an assessment of the influence of specific HMOS on the growth and metabolic products of individual microbiota bacteria. Most Bifidobacteria spp. and Bacteroides spp. grew, induced α-L-fucosidase activity, and produced abundant lactate or short-chain fatty acids (SCFAs) when fed 2'-fucosyllactose (2'-FL), 3-FL, and lactodifucotetraose (LDFT). Lactobacillus delbrueckii ATCC7830, Enterococcus faecalis ATCC19433, and Streptococcus thermophilus ATCC19258 exhibited slight growth, pH reduction, and lactate production when supplemented with 2'-FL or 3-FL, but not LDFT. Supplementation with 3'-sialyllactose (3'-SL) and 6'-SL promoted moderate growth of Bifidobacterium longum JCM7007, 7009, 7010, 7011, 1272, 11347, ATCC15708, Bacteroides vulgatus ATCC8482, and B. thetaiotaomicron ATCC29148; accordingly, these bacteria exhibited greater neuraminidase activity and produced copious lactate, SCFA, or both. Lactobacillus delbrueckii ATCC7830 also consumed 6'-SL. In contrast, Clostridium spp., L. rhamnosus ATCC53103, E. faecalis ATCC29200, Staphylococcus spp., Enterobacter spp., and Escherichia coli K12 did not consume milk oligosaccharides nor produce appreciable acidic fermentation products. Specific Bifidobacteria and Bacteroides differentially digest specific individual HMOS, with the major fucosylated milk oligosaccharides most strongly stimulating key species of mutualist symbionts. This suggests strategies for treating dysbiosis of the microbiota and associated inflammatory disorders.

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

“…The ability of 2#-FL to inhibit C. jejuni binding is consistent with the inverse relation between concentrations of 2-linked fucosyl oligosaccharides in milk consumed by infants and the risk of C. jejuni-caused moderate-tosevere diarrhea in a prospective study in breastfeeding motherinfant dyads (16,17). Prebiotic activity of oligosaccharides also may be protective (18,19); these indigestible glycans provide a carbon source for mutualistic bacteria that promote the colonization of the gut by a protective community of microbes.…”

Cross-feeding interactions of gut symbionts driven by human milk oligosaccharidesand mucins

“…The Sus system thus appeared to be an efficient and well-coordinated machinery to sequester HMOS by employing the mucusutilisation machinery (Marcobal et al 2011). In the co-culture with Anaerostipes caccae, We found that Bacteroides thetaiotaomicron effectively utilised most of the low molecular weight HMOS as previously reported (Yu et al 2013), with differential preference for specific HMOS structures. The glycan-foraging capability could enhance the bacterial fitness and colonisation in the infant gut (Martens et al 2008) and the finestructure prioritisation at species level has been accounted for the collective fitness of Bacteroides spp.…”

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

“…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).…”

“…Thus, HMOS and their major fucosylated components are prebiotic to the mutualists and the mutualist fermentation products inhibit pathogens and opportunists. Moreover, HMOSs, and especially fucosylated HMOSs could promote the growth of specific pioneering or keystone species of human microbiota, thereby shaping birth and milk inocula into a mutualist symbiotic microbiota (32). This is a potential mechanism whereby human milk could confer long term beneficial effects on infant health well after weaning.…”