scholarly journals 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

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 71 ◽  
Author(s):  
Mikiyasu Sakanaka ◽  
Aina Gotoh ◽  
Keisuke Yoshida ◽  
Toshitaka Odamaki ◽  
Hiroka Koguchi ◽  
...  
Keyword(s):  
Human Milk ◽  
Future Perspectives ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Probiotic Supplementation ◽  
Formula Milk ◽  
Fecal Microbiome ◽  
The Third ◽  
Bifidobacterium Species ◽  
Gene Sets

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.

Diversification of a fucosyllactose transporter within the genus Bifidobacterium

2021 ◽  
Author(s):  
Miriam N. Ojima ◽  
Yuya Asao ◽  
Aruto Nakajima ◽  
Toshihiko Katoh ◽  
Motomitsu Kitaoka ◽  
...  
Keyword(s):  
Human Milk ◽  
Binding Proteins ◽  
Heterologous Gene Expression ◽  
Metagenomic Data ◽  
Dependent Manner ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Formula Milk ◽  
Breastfed Infants ◽  
Strain Dependent

Human milk oligosaccharides (HMOs), which are natural bifidogenic prebiotics, were recently commercialized to fortify formula milk. However, HMO-assimilation phenotypes of bifidobacteria vary by species and strain, which has not been fully linked to strain genotype. We have recently shown that specialized uptake systems, particularly for the internalization of major HMOs (fucosyllactose (FL)), are associated with the formation of a bifidobacteria-rich gut microbial community. Phylogenetic analysis has revealed that FL transporters have diversified into two clades harboring four clusters within the Bifidobacterium genus, but the underpinning functional diversity associated with this divergence remains underexplored. In this study, we examined the HMO-consumption phenotypes of two bifidobacterial species, Bifidobacterium catenulatum subspecies kashiwanohense and Bifidobacterium pseudocatenulatum , which both possess FL binding proteins that belong to phylogenetic clusters with unknown specificities. Growth assays, heterologous gene expression experiments, and HMO-consumption analysis showed that the FL transporter type from B. catenulatum subspecies kashiwanohense JCM 15439 T conferred a novel HMO-uptake pattern that includes the complex fucosylated HMOs (lacto- N- fucopentaose II and lacto- N- difucohexaose I/II). Further genomic landscape analyses of FL transporter-positive bifidobacterial strains revealed that H-antigen or Lewis antigen-specific fucosidase gene(s) and FL transporter specificities were largely aligned. These results suggest that bifidobacteria have acquired FL transporters along with the corresponding gene sets necessary to utilize the imported HMOs. Our results provide insight into the species- and strain-dependent adaptation strategies of bifidobacteria to HMO-rich environments. Importance The gut of breastfed infants is generally dominated by health-promoting bifidobacteria. Human milk oligosaccharides (HMOs) from breastmilk selectively promote the growth of specific taxa such as bifidobacteria, thus forming an HMO-mediated, host-microbe symbiosis. While the co-evolution of humans and bifidobacteria has been proposed, the underpinning adaptive strategies employed by bifidobacteria require further research. Here, we analyzed the divergence of the critical fucosyllactose (FL) HMO transporter within Bifidobacterium . We have shown that the diversification of the solute-binding proteins of the FL-transporter led to uptake specificities of fucosylated sugars ranging from simple trisaccharides to complex hexasaccharides. This transporter and the congruent acquisition of the necessary intracellular enzymes allows for bifidobacteria to import different types of HMOs in a predictable and strain-dependent manner. These findings explain the adaptation and proliferation of bifidobacteria in the competitive and HMO-rich infant gut environment and enable accurate specificity annotation of transporters from metagenomic data.

scholarly journals Relationship between human milk oligosaccharides and fecal microbiome of breastfed infants

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Janet E Williams ◽  
Mara A Riley ◽  
Sarah L Brooker ◽  
Katherine M Hunt ◽  
Alexandra Szyszka ◽  
...  
Keyword(s):  
Human Milk ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Fecal Microbiome ◽  
Breastfed Infants

scholarly journals A safety evaluation of mixed human milk oligosaccharides in neonatal farm piglets

2020 ◽  
Vol 4 ◽  
pp. 239784732097125
Author(s):  
Paul R Hanlon
Keyword(s):  
Human Milk ◽  
Feed Efficiency ◽  
Clinical Chemistry ◽  
Control Diet ◽  
Safety Evaluation ◽  
Efficiency Analysis ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
The Third ◽  
Microscopic Inspection

Human Milk Oligosaccharides (HMOs) are the third most abundant, solid component of human milk after lactose and fat. As novel processes are developed to cost-effectively produce commercial volumes of these oligosaccharides, they are becoming more common components of infant formulas worldwide. The study evaluated the safety of a novel mixture of HMOs in a neonatal piglet model with the objective of identifying potential effects during the sensitive, preweaning developmental stage of life. The mixture of HMOs (HMO MIX 1) was composed of 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), 3′-sialyllactose (3′-SL), and 6′-sialyllactose (6′-SL), and was administered to 2-day old piglets at either 5.75 or 8.0 g/L for a period of 21 days. Piglets in the 5.75 and 8.0 g/L HMO MIX 1 dosing groups did not exhibit differences in body weight, food consumption, or feed efficiency. Analysis of clinical chemistry parameters on Study Day 7 and Study Day 21 did not demonstrate any effects that could be attributed to HMO MIX 1, nor were there any findings in organ weight, macroscopic, or microscopic inspection of tissues that could be attributed to this oligosaccharide blend. Therefore, since administration of HMO MIX 1 in a liquid diet up to 8.0 g/L resulted in no toxicologically-relevant effects in comparison with animals fed a control diet, this study supports the safety of this ingredient for addition to infant formula products.

scholarly journals Human Milk Oligosaccharides: A Comprehensive Review towards Metabolomics

Children ◽  
2021 ◽  
Vol 8 (9) ◽  
pp. 804
Author(s):  
Laura Corona ◽  
Anna Lussu ◽  
Alice Bosco ◽  
Roberta Pintus ◽  
Flaminia Cesare Marincola ◽  
...  
Keyword(s):  
Breast Milk ◽  
Human Milk ◽  
Genetic Factors ◽  
Environmental Influence ◽  
Protective Role ◽  
Point Of View ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
The Third

Human milk oligosaccharides (HMOs) are the third most represented component in breast milk. They serve not only as prebiotics but they exert a protective role against some significant neonatal pathologies such as necrotizing enterocolitis. Furthermore, they can program the immune system and consequently reduce allergies and autoimmune diseases’ incidence. HMOs also play a crucial role in brain development and in the gut barrier’s maturation. Moreover, the maternal genetic factors influencing different HMO patterns and their modulation by the interaction and the competition between active enzymes have been widely investigated in the literature, but there are few studies concerning the role of other factors such as maternal health, nutrition, and environmental influence. In this context, metabolomics, one of the newest “omics” sciences that provides a snapshot of the metabolites present in bio-fluids, such as breast milk, could be useful to investigate the HMO content in human milk. The authors performed a review, from 2012 to the beginning of 2021, concerning the application of metabolomics to investigate the HMOs, by using Pubmed, Researchgate and Scopus as source databases. Through this technology, it is possible to know in real-time whether a mother produces a specific oligosaccharide, keeping into consideration that there are other modifiable and unmodifiable factors that influence HMO production from a qualitative and a quantitative point of view. Although further studies are needed to provide clinical substantiation, in the future, thanks to metabolomics, this could be possible by using a dipstick and adding the eventual missing oligosaccharide to the breast milk or formula in order to give the best and the most personalized nutritional regimen for each newborn, adjusting to different necessities.

scholarly journals Effects of Different Human Milk Oligosaccharides on Growth of Bifidobacteria in Monoculture and Co-culture With Faecalibacterium prausnitzii

2020 ◽  
Vol 11 ◽  
Author(s):  
Lianghui Cheng ◽  
Mensiena B. G. Kiewiet ◽  
Madelon J. Logtenberg ◽  
Andre Groeneveld ◽  
Arjen Nauta ◽  
...  
Keyword(s):  
Human Milk ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Faecalibacterium Prausnitzii

scholarly journals Regulation of hBD-2, hBD-3, hCAP18/LL37, and Proinflammatory Cytokine Secretion by Human Milk Oligosaccharides in an Organotypic Oral Mucosal Model

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 739
Author(s):  
Ulvi K. Gürsoy ◽  
Krista Salli ◽  
Eva Söderling ◽  
Mervi Gürsoy ◽  
Johanna Hirvonen ◽  
...  
Keyword(s):  
Human Milk ◽  
Expression Profiles ◽  
Three Dimensional ◽  
Human Milk Oligosaccharides ◽  
Proinflammatory Response ◽  
Milk Oligosaccharides ◽  
Culture Model ◽  
Gingival Cells ◽  
Mucosal Secretion ◽  
Immunomodulatory Potential

Human milk oligosaccharides (HMOs), the third largest solid fraction in human milk, can modulate inflammation through Toll-like receptor signaling, but little is known about their immunomodulatory potential in the oral cavity. In this study, we determined whether the HMOs 2’-fucosyllactose (2’-FL) and 3-fucosyllactose (3-FL) regulate human-beta defensin (hBD)-2 and -3, cathelicidin (hCAP18/LL-37), and cytokine responses in human gingival cells using a three-dimensional oral mucosal culture model. The model was incubated with 0.1% or 1% 2’-FL and 3-FL, alone and in combination, for 5 or 24 h, and hBD-2, hBD-3, and hCAP18/LL-37 were analyzed by immunohistochemistry. The expression profiles of interleukin (IL)-1, IL-1RA, IL-8, and monocyte chemoattractant protein (MCP)-1 were determined by LUMINEX immunoassay. The combination of 1% 2’-FL and 1% 3-FL, and 1% 3-FL alone, for 24 h upregulated hBD-2 protein expression significantly (p < 0.001 and p = 0.016, respectively). No changes in the other antimicrobial peptides or proinflammatory cytokines were observed. Thus, 3-FL, alone and in combination with 2´-FL, stimulates oral mucosal secretion of hBD-2, without effecting a proinflammatory response when studied in an oral mucosal culture model.

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