Human milk and mucosa-associated disaccharides impact on cultured infant fecal microbiota

Abstract

Human milk oligosaccharides (HMOs) are a mixture of structurally diverse carbohydrates that contribute to shape a healthy gut microbiota composition. The great diversity of the HMOs structures does not allow the attribution of specific prebiotic characteristics to single milk oligosaccharides. We analyze here the utilization of four disaccharides, lacto- N -biose (LNB), galacto- N -biose (GNB), fucosyl-α1,3-GlcNAc (3FN) and fucosyl-α1,6-GlcNAc (6FN), that form part of HMOs and glycoprotein structures, by the infant fecal microbiota. LNB significantly increased the total levels of bifidobacteria and the species Bifidobacterium breve and Bifidobacterium bifidum . The Lactobacillus genus levels were increased by 3FN fermentation and B. breve by GNB and 3FN. There was a significant reduction of Blautia coccoides group with LNB and 3FN. In addition, 6FN significantly reduced the levels of Enterobacteriaceae family members. Significantly higher concentrations of lactate, formate and acetate were produced in cultures containing either LNB or GNB in comparison with control cultures. Additionally, after fermentation of the oligosaccharides by the fecal microbiota, several Bifidobacterium strains were isolated and identified. The results presented here indicated that each, LNB, GNB and 3FN disaccharide, might have a specific beneficial effect in the infant gut microbiota and they are potential prebiotics for application in infant foods.

Infant gut microbiota modulation by human milk disaccharides in humanized microbiome mice

“… 43 Using in vitro fermentation analysis, our group and others have demonstrated that LNB is metabolized by infant-gut associated bifidobacteria. 24 , 27 Here, this disaccharide is tested for the first time using an in vivo model and it has been demonstrated that it significantly increased the relative abundance of the genus Bifidobacterium in feces. However, the absolute levels of this genus in the LNB mice group were similar to the control group (Supplemental Figure 3 ), suggesting that the high relative abundance of Bifidobacterium in LNB could be due to reductions in the relative abundances of other taxa.…”

“… 44 Indeed, a B. longum strain isolated from fermented cultures with infant gut microbiota was able to grow in the presence of GNB. 24 The positive effect of LNB, GNB or 6FN in the persistence of B. longum species in the gastrointestinal tract is a relevant outcome, since this bacterium has been widely associated with prevention and fighting of several intestinal and immune diseases. 45 , 46 Regarding B. adolescentis species, it has been shown previously that this species is not able to metabolize 3FN and 6FN.…”

“…The disaccharides fucosyl-α1,3-GlcNAc (3FN) and fucosyl-α1,6-GlcNAc (6FN) that form part of HMOs and core-fucosylated N -glycans, respectively, have been synthetized in our laboratory. 22 , 23 In vitro fermentation analysis, using pure cultures 23 and batch cultures with infant fecal microbiota, 24 has demonstrated that 3FN stimulates the growth of the species Lactobacillus casei and Bifidobacterium breve , respectively. We have also produced lacto- N -biose (LNB; Gal- β1,3-GlcNAc), the main building block of type-1 HMOs, and galacto- N -biose (GNB; Gal- β1,3-GalNAc), the core type-1 sugar from mucins.…”

“… 26 Both disaccharides have been shown to efficiently promote in vitro the growth of specific Bifidobacterium species. 24 , 27 In this work, a humanized mouse model, which was generated by infant fecal microbiota transplantation, was utilized to evaluate the effects of 3FN, 6FN, LNB and GNB on the development of the gut microbiota composition ( Figure 1 ). Short-chain fatty acids production and interactions host–microbiota, through the assessment of serum lipid profile and cytokines expression, were also measured.…”

Identification of Synbiotics Conducive to Probiotics Adherence to Intestinal Mucosa Using an In Vitro Caco-2 and HT29-MTX Cell Model

“…Notably, this differs from the consistent anti-adhesive effects observed in the present study, which utilized purified HMOs rather than whole milk. Thus, despite the recent progress in the study of the individual HMO components and their influence on bacterial growth (e.g., [45]), additional research is required to clarify their collective influence on functional probiotic characteristics such as bacterial adhesion ability.…”