Varied Pathways of Infant Gut-Associated Bifidobacterium to Assimilate Human Milk Oligosaccharides: Prevalence of the Gene Set and Its Correlation with Bifidobacteria-Rich Microbiota Formation

Abstract

The infant’s gut microbiome is generally rich in the Bifidobacterium genus. The mother’s milk contains natural prebiotics, called human milk oligosaccharides (HMOs), as the third most abundant solid component after lactose and lipids, and of the different gut microbes, infant gut-associated bifidobacteria are the most efficient in assimilating HMOs. Indeed, the fecal concentration of HMOs was found to be negatively correlated with the fecal abundance of Bifidobacterium in infants. Given these results, two HMO molecules, 2′-fucosyllactose and lacto-N-neotetraose, have recently been industrialized to fortify formula milk. As of now, however, our knowledge about the HMO consumption pathways in infant gut-associated bifidobacteria is still incomplete. The recent studies indicate that HMO assimilation abilities significantly vary among different Bifidobacterium species and strains. Therefore, to truly maximize the effects of prebiotic and probiotic supplementation in commercialized formula, we need to understand HMO consumption behaviors of bifidobacteria in more detail. In this review, we summarized how different Bifidobacterium species/strains are equipped with varied gene sets required for HMO assimilation. We then examined the correlation between the abundance of the HMO-related genes and bifidobacteria-rich microbiota formation in the infant gut through data mining analysis of a deposited fecal microbiome shotgun sequencing dataset. Finally, we shortly described future perspectives on HMO-related studies.

Enzymatic Adaptation of Bifidobacterium bifidum to Host Glycans, Viewed from Glycoside Hydrolyases and Carbohydrate-Binding Modules

“…These results indicate that the utilization of GNB/LNB was not prioritized by B. longum in the presence of many other sugars, such as Gal, GlcNAc, or lactose released from HMOs/mucin O-glycans under our experimental conditions. It should be noted that the growth ability on LNB was completely abrogated by the disruption of gltA (Supplementary Figure S1), which is well-conserved among the infant gut-associated Bifidobacterium [11,96]. (A,B) or spectinomycin (C-F) resistance gene on a plasmid (pBFS38 or pBFO2, respectively) [97] was used for monitoring the growth.…”

“…longum (B. longum), are frequently detected in the stool of breast-fed infants. Many studies [9][10][11][12][13][14][15][16][17][18][19] have indicated that the formation of a bifidus-flora in the gut of breast-fed infants can be attributed to human milk oligosaccharides (HMOs), which are the third most abundant solid component in breastmilk after lactose and lipids [20][21][22]. Mothers produce the energy-rich HMOs, even though HMOs have no direct nutritional value for infants, as HMOs are resistant to digestive enzymes secreted in the gastrointestinal tract.…”

“…Recent studies have unequivocally revealed that HMOs are utilized by infant gut-associated bifidobacteria to proliferate in their specific ecosystem [23,24]. Interestingly, the pathways for HMO assimilation differ among the Bifidobacterium species and even among strains of the same species, suggesting strong selective pressure and adaptive evolution under symbioses with individuals with different gut environments [11,13]. After weaning, the bifidobacterial population gradually decreases and its dominance is replaced with other microbes that are adapted to plant-derived glycan utilization, such as Bacteroides and Clostridium, to form an adult-type microbiota.…”

“…Among Bifidobacterium species, B. bifidum is quite unique in that this species possesses many extracellular glycosidases specified for degrading host-derived glycans, including HMOs, the sugar chains of high molecular-weight glycoproteins, and glycosphingolipids [11,[25][26][27]. B. bifidum liberates mono-and disaccharides from host glycans and releases them into the living environmental niches or culture medium in vitro.…”

The Impact of Dietary Fucosylated Oligosaccharides and Glycoproteins of Human Milk on Infant Well-Being

“…present in the digestive tract of newborns and infants differ in their ability to use and/or digest HMOs. In comparison with Lactobacillus gasseri, Bifidobacterium infantis has an excellent ability to digest HMOs [91,92]. The genome of B. infantis encodes 24 different glycosidases, responsible for cleaving individual monosaccharide units from oligosaccharides, including 2α-sialidase and 5α-L-fucosidase ( Figure 2) [85,[91][92][93].…”