Identification of genes involved in galactooligosaccharide utilization in Bifidobacterium breve strain YIT 4014T

Sotoya, Hidetsugu; Shigehisa, Akira; Hara, Takeo; Matsumoto, Hoshitaka; Hatano, Hiroshi

doi:10.1099/mic.0.000517

Cited by 18 publications

(16 citation statements)

References 26 publications

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“…In the formula-fed infant group (the USA only), the abundance of Bifidobacterium appeared to show strong positive correlations with those of GOS transporter genes with statistical significance [47,75] ( Figure 4B; Spearman's rank correlation coefficient). GOSs are world-wide prebiotics supplemented in infant formula and are known to increase the population of bifidobacteria in the guts [76,77].…”

Section: Abundance Of Hmo-related Genes Is Associated With Bifidobactmentioning

confidence: 99%

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

et al. 2019

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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.

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Section: Abundance Of Hmo-related Genes Is Associated With Bifidobactmentioning

confidence: 99%

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

et al. 2019

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“…Different ABC transporters appear to mediate this utilization, and the closest homolog of Bal6GBP (WP_003828494.1; amino acid sequence identity 76%) showed the highest affinity for ␤-(1,6)-GL (K D ϭ 0.357 M). This protein has a markedly different selectivity as compared with Bal6GBP, based on a decrease in affinity of only 16-fold for ␤-(1,4)-GL and 460-fold lower affinity for ␤-(1,3)-GL (22). The shared preference for ␤-(1,6)-galactosides, but large selectivity differences, are consistent with these SBPs populating different branches in the same clade in the phylogenetic tree (clade 1, Fig.…”

Section: The Selectivity Of Transport Binding Proteins Correlates To mentioning

confidence: 98%

“…lactis grows well on ␤-(1,6)galactosyl lactose, but not on the ␤-(1,4) version of this trisaccharide (both from bovine milk)) (36). Recent studies have identified an ABC transporter that mediates the uptake of ␤-(1,6)-galactosyl-lactose from B. breve and characterized the preference of the associated SBP (22,37). Notably, B. breve was EDITORS' PICK: ␤-Galactoside capture in B. animalis subsp.…”

Section: The Selectivity Of Transport Binding Proteins Correlates To mentioning

confidence: 99%

“…Knowledge about ␤-galactoside preferences of bifidobacteria largely stems from characterization of ␤-galactosidases (20) or from growth and oligosaccharide consumption profiles (19). The role of oligosaccharide transporters in ␤-galactooligosaccharide utilization selectivity has received less attention, with two recent studies having addressed the identification and binding properties of ␤-galactooligosaccharide transport proteins in Bifidobacterium breve (21,22).…”

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confidence: 99%

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Substrate preference of an ABC importer corresponds to selective growth on β-(1,6)-galactosides in Bifidobacterium animalis subsp. lactis

Theilmann

Fredslund

Svensson

et al. 2019

Journal of Biological Chemistry

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Bifidobacteria are exposed to substantial amounts of dietary ␤-galactosides. Distinctive preferences for growth on different ␤-galactosides are observed within Bifidobacterium members, but the basis of these preferences remains unclear. We previously described the first ␤-(1,6)/(1,3)-galactosidase from Bifidobacterium animalis subsp. lactis Bl-04. This enzyme is relatively promiscuous, exhibiting only 5-fold higher efficiency on the preferred ␤-(1,6)-galactobiose than the ␤-(1,4) isomer. Here, we characterize the solute-binding protein (Bal6GBP) that governs the specificity of the ABC transporter encoded by the same ␤-galactoside utilization locus. We observed that although Bal6GBP recognizes both ␤-(1,6)and ␤-(1,4)-galactobiose, Bal6GBP has a 1630-fold higher selectivity for the former, reflected in dramatic differences in growth, with several hours lag on less preferred ␤-(1,4)and ␤-(1,3)-galactobiose. Experiments performed in the presence of varying proportions of ␤-(1,4)/␤-(1,6)-galactobioses indicated that the preferred substrate was preferentially depleted from the culture supernatant. This established that the poor growth on the nonpreferred ␤-(1,4) was due to inefficient uptake. We solved the structure of Bal6GBP in complex with ␤-(1,6)-galactobiose at 1.39 Å resolution, revealing the structural basis of this strict selectivity. Moreover, we observed a close evolutionary relationship with the human milk disaccharide lacto-N-biose-binding protein from Bifidobacterium longum, indicating that the recognition of the nonreducing galactosyl is essentially conserved, whereas the adjacent position is diversified to fit different glycosidic linkages and monosaccharide residues. These findings indicate that oligosaccharide uptake has a pivotal role in governing selectivity for distinct growth substrates and have uncovered evolutionary trajectories that shape the diversification of sugar uptake proteins within Bifidobacterium.

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“…inulin, fructo‐oligosaccharides (FOS), galacto‐oligosaccharides (GOS), and lactulose . These saccharides selectively promote probiotic bacteria, as these bacteria often uniquely express special transporters to bind and uptake them and enzymes to utilize them . However, none of the existing prebiotic solutions for modulation of the gut microbiota contains a protein source.…”

Section: Introductionmentioning

confidence: 99%

Protein‐oligosaccharide conjugates as novel prebiotics

Seifert

Freilich

Kashi

2019

Polymers for Advanced Techs

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Maintaining a good proportion of gut probiotic bacteria is imperative to health. This may be achieved by consuming “prebiotics,” e.g., galacto‐oligosaccharides (GOS) that selectively promote probiotic bacteria, as they often uniquely express transporters for such oligosaccharides. Proteins are an important source for amino acids essential to probiotic bacteria. As most protein digestion products are absorbed in the small intestine, and there is great competition on the residuals by colonic bacteria, amino acids are scarce (<0.01 mM) in the colonic intercellular fluid, thus limiting probiotics' proliferation. However, no existing prebiotic product contains protein. Herein, we propose a new type of prebiotics: protein‐oligosaccharide conjugates. These conjugates were designed to be selectively targeted to probiotic bacteria in the colon, for enhancing their competitive advantage over undesired microorganisms. The approach was inspired by active targeting of chemotherapy, achieved by conjugating drugs to ligands, which selectively bind to proteins uniquely expressed on cancer cells; except here, we aimed to promote, not eliminate, the targeted cells. We formed these conjugates by mild Maillard‐reaction‐based covalent conjugation of GOS to lactoferrin hydrolysate (LFH), formed by peptic digestion, hence it resists gastric digestion. LFH‐GOS conjugates comprised 76% ± 1% LFH and 25% ± 4% GOS, and self‐assembled into 0.2 to 1.5‐μm microparticles. Most of the conjugates' protein content endured simulated gastrointestinal digestion, hence is expected to reach the colon. Remarkably, we found that the growth rate of a model probiotic bacterium (Lactobacillus casei) on the conjugates was double that on the unconjugated components (0.082 and 0.041 h−1, respectively). This study proposes the next generation of prebiotics.

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Identification of genes involved in galactooligosaccharide utilization in Bifidobacterium breve strain YIT 4014T

Cited by 18 publications

References 26 publications

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

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

Substrate preference of an ABC importer corresponds to selective growth on β-(1,6)-galactosides in Bifidobacterium animalis subsp. lactis

Protein‐oligosaccharide conjugates as novel prebiotics

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