94 research outputs found

    Ser dona, un desafiament; ser home, un avantatge

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    Integrating the Ecosystem Services Framework to Define Dysbiosis of the Breastfed Infant Gut: The Role of B. infantis and Human Milk Oligosaccharides

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    Mounting evidence supports a connection between the composition of the infant gut microbiome and long-term health. In fact, aberrant microbiome compositions during key developmental windows in early life are associated with increased disease risk; therefore, making pertinent modifications to the microbiome during infancy offers significant promise to improve human health. There is growing support for integrating the concept of ecosystem services (the provision of benefits from ecosystems to humans) in linking specific microbiome functions to human well-being. This framework is widely applied in conservation efforts of macro-ecosystems and offers a systematic approach to guide restoration actions aimed to recover critical ecological functions. The aim of this work is to apply the ecosystem services framework to integrate recent studies demonstrating stable alteration of the gut microbiome of breastfed infants when Bifidobacterium longum subsp. infantis EVC001, a gut symbiont capable of efficiently utilizing human milk oligosaccharides into organic acids that are beneficial for the infant and lower intestinal pH, is reintroduced. Additionally, using examples from the literature we illustrate how the absence of B. infantis results in diminished ecosystem services, which may be associated with health consequences related to immune and metabolic disorders. Finally, we propose a model by which infant gut dysbiosis can be defined as a reduction in ecosystem services supplied to the host by the gut microbiome rather than merely changes in diversity or taxonomic composition. Given the increased interest in targeted microbiome modification therapies to decrease acute and chronic disease risk, the model presented here provides a framework to assess the effectiveness of such strategies from a host-centered perspective

    Colonization of breastfed infants by Bifidobacterium longum subsp. infantis EVC001 reduces virulence gene abundance

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    The infant gut microbiome is rapidly colonized by bacteria from the environment after birth, and this gut ecosystem can facilitate expansion of potential pathogens. Human milk shapes the infant gut microbiome and has evolved to foster the growth of specific bacteria. Breastfed infants fed the coevolved infant gut symbiont Bifidobacterium longum subsp. infantis EVC001 had significant modifications to their gut metagenome, including a decreased number of virulence factor genes

    Reduced colonic mucin degradation in breastfed infants colonized by \u3ci\u3eBifidobacterium longum\u3c/i\u3e subsp. \u3ci\u3einfantis\u3c/i\u3e EVC001

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    Mucin glycoproteins play an important role in protecting the gut epithelium by keeping gut microbes from direct contact with the gut epithelium while allowing for diffusion of small molecules from the lumen to the epithelium. The mucin glycocalyx can be degraded by gut bacteria such as Bacteroides and Akkermansia, but other bacteria, such as Bifidobacterium longum subsp. Infantis, cannot consume mucin glycans. Untargeted mass spectrometry profiles were compared to microbiome profiles to assess how different gut microbiomes affect colonic mucin degradation. Samples obtained from nine infants colonized by Bifidobacterium infantis EVC001 and from 10 infants colonized by higher levels of mucolytic taxa (controls), including Bacteroides, were compared. Previously performed untargeted nano-high-performance liquid chromatography-chip/time-of-flight mass spectrometry was used to detect and quantify glycans originating from colonic mucin. Colonic mucin-derived O-glycans from control infants composed 37.68% (± 3.14% SD) of the total glycan structure pool, whereas colonic mucin-derived O-glycans made up of only 1.78% (± 0.038% SD) of the total in B. infantis EVC001 samples. The relative abundance of these colonic mucin-derived O-glycans in the total glycan pool was higher among control, 26.98% (± 8.48% SD), relative to B. infantis-colonized infants, 1.68% (± 1.12% SD). Key taxa, such as Bacteroidaceae, were significantly and positively correlated with the abundance of these structures, while Bifidobacteriaceae were significantly and negatively associated with these structures. These results suggest that colonization of infants by B. infantis may diminish colonic glycan degradation and help maintain barrier function in the gastrointestinal tract of infants

    Prostaglandin D2 synthase induces apoptosis in pig kidney LLC-PK1 cells

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    Prostaglandin D2 synthase induces apoptosis in pig kidney LLC-PK1 cells.BackgroundProstaglandin D2 synthase (PGD2S), a unique member of the lipocalin family, is found at elevated levels in the serum of patients with renal impairment and has recently been implicated as a new biochemical marker of renal insufficiency. The aim of this study was to investigate the apoptotic effects of PGD2S on a pig kidney epithelial cell line (LLC-PK1) and to investigate the effects of prostaglandins and growth factors on this process.MethodsApoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL), annexin V staining, and electron microscopy.ResultsA four- to fivefold increase in apoptosis was observed in PGD2S-treated cells as compared with controls and the apoptosis appeared to act via caspase-3. A cyclooxygenase-2 inhibitor, anti-PGD2S antibody, and selenium all significantly inhibited the apoptosis induced by PGD2S; however, none had any effect on the apoptosis induced by the known apoptotic inducer camptothecin. Furthermore, prostaglandins E1 and E2, known to induce mitogen-activated protein (MAP) kinase phosphorylation and exhibit cytoprotective effects, both inhibited PGD2S-induced apoptosis, while prostaglandin H2 had no significant effect. Growth factors such as insulin, insulin-like growth factor-1, and platelet-derived growth factor also decreased PGD2S-induced apoptosis. In addition, PGD2S isolated from human serum seemed slightly more effective at inducing apoptosis than recombinantly expressed protein.ConclusionsWe report on the induction of apoptosis by PGD2S in LLC-PK1 pig kidney epithelial cells, and speculate that the accumulation of PGD2S in the serum of kidney failure patients may further exacerbate renal problems and is most likely regulated by other prostaglandins and growth factors

    N-glycans from human milk glycoproteins are selectively released by an infant gut symbiont in vivo

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    Complex, indigestible free oligosaccharides as well as conjugated glycans are found in milk that shape the gut microbiome of infants. The activity of an endo-β-N-acetylglucosaminidase from B. longum subsp. infantis (B. infantis) is known to release N-glycans from native milk glycoproteins under physiological conditions. We investigated whether this enzyme is active in vivo in breastfed infants fed B. infantis EVC001. Using mass spectrometry, we found 19 N-glycans related to human milk glycoproteins increased in abundance, similar to previous work using bovine milk glycoproteins, and these 19 N-glycans matched unique specificities of this enzyme. Twenty N-glycans were unique to infants fed B. infantis EVC001. Bifidobacteriaceae were correlated with these glycans, confirming the relationship between B. infantis and released N-glycans. This suggests that this enzyme is active in vivo and releases N-glycans from milk glycoproteins, and may play a role in B. infantis EVC001 colonization of the gut microbiome

    Potential Applications of Endo-B-N-Acetylglucosaminidases From Bifidobacterium longum Subspecies infantis in Designing Value-Added, Next-Generation Infant Formulas

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    Human milk is the optimal source of infant nutrition. Among many other health benefits, human milk can stimulate the development of a Bifidobacterium-rich microbiome through human milk oligosaccharides (HMOs). In recent years, the development of novel formulas has placed particular focus on incorporating some of the beneficial functional properties of human milk. These include adding specific glycans aimed to selectively stimulate the growth of Bifidobacterium. However, the bifidogenicity of human milk remains unparalleled. Dietary N-glycans are carbohydrate structures conjugated to a wide variety of glycoproteins. These glycans have a remarkable structural similarity to HMOs and, when released, show a strong bifidogenic effect. This review discusses the biocatalytic potential of the endo-B-N-acetylglucosaminidase enzyme (EndoBI-1) from Bifidobacterium longum subspecies infantis (B. infantis), in releasing N-glycans inherently present in infant formula as means to increase the bifidogenicity of infant formula. Finally, the potential implications for protein deglycosylation with EndoBI-1 in the development of value added, next-generation formulas are discussed from a technical perspective

    Bovine Colostrum and Its Potential for Human Health and Nutrition

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    Colostrum is the first milk produced post-partum by mammals and is compositionally distinct from mature milk. Bovine colostrum has a long history of consumption by humans, and there have been a number of studies investigating its potential for applications in human nutrition and health. Extensive characterization of the constituent fractions has identified a wealth of potentially bioactive molecules, their potential for shaping neonatal development, and the potential for their application beyond the neonatal period. Proteins, fats, glycans, minerals, and vitamins are abundant in colostrum, and advances in dairy processing technologies have enabled the advancement of bovine colostrum from relative limitations of a fresh and unprocessed food to a variety of potential applications. In these forms, clinical studies have examined bovine colostrumas having the substantial potential to improve human health. This review discusses the macro-and micronutrient composition of colostrum as well as describing well-characterized bioactives found in bovine colostrum and their potential for human health. Current gaps in knowledge are also identified and future directions are considered in order to elevate the potential for bovine colostrum as a component of a healthy diet for a variety of relevant human populations

    Comparative Genome Analysis of Bifidobacterium longum subsp. infantis Strains Reveals Variation in Human Milk Oligosaccharide Utilization Genes among Commercial Probiotics

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    Dysbiosis is associated with acute and long-term consequences for neonates. Probiotics can be effective in limiting the growth of bacteria associated with dysbiosis and promoting the healthy development of the infant microbiome. Given its adaptation to the infant gut, and promising data from animal and in vitro models, Bifidobacterium longum subsp. infantis is an attractive candidate for use in infant probiotics. However, strain-level differences in the ability of commercialized strains to utilize human milk oligosaccharides (HMOs) may have implications in the performance of strains in the infant gut. In this study, we characterized twelve B. infantis probiotic strains and identified two main variants in one of the HMO utilization gene clusters. Some strains possessed the full repertoire of HMO utilization genes (H5-positive strains), while H5-negative strains lack an ABC-type transporter known to bind core HMO structures. H5-positive strains achieved significantly superior growth on lacto-N-tetraose and lacto-N-neotetraose. In vitro, H5-positive strains had a significant fitness advantage over H5-negative strains, which was also observed in vivo in breastfed infants. This work provides evidence of the functional implications of genetic dierences among B. infantis strains and highlights that genotype and HMO utilization phenotype should be considered when selecting a strain for probiotic use in infants
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