Variability of Human Milk Neutral Oligosaccharides in a Diverse Population

Erney, R.; Malone, W T; Skelding, Mary-Beth; Marcon, Andrea; Kleman-Leyer, K M; O’Ryan, Miguel; Ruíz-Palacios, Guillermo M.; Hilty, Markus; Pickering, Larry K.; Prieto, P.

doi:10.1097/00005176-200002000-00016

Cited by 202 publications

(256 citation statements)

References 42 publications

Supporting

Mentioning

228

Contrasting

Order By: Relevance

“…Thus, the clustering we observed according to W143X genotype might be explained by the common presence/absence of preferred attachment site(s), which are, in several cases, fucosylated glycoconjugates (45). We hypothesize that the glycoconjugate profile of the mucosa of heterozygotes (Sese) may differ from each respective homozygote, for example, via competition for substrates with other glycosyltransferases expressed in the GI tract, resulting in an influence on the availability of bacterial attachment sites or nutritional resources (46). Variation in α-1,2-fucosyltransferase activity was observed in fucosylated milk proteins, and it is hypothesized that variation not only at the level of secretor status but also at the level of genotype plays an important role in determining which substrates are glycosylated by the same set of enzymes (46).…”

Section: Discussionmentioning

confidence: 93%

“…We hypothesize that the glycoconjugate profile of the mucosa of heterozygotes (Sese) may differ from each respective homozygote, for example, via competition for substrates with other glycosyltransferases expressed in the GI tract, resulting in an influence on the availability of bacterial attachment sites or nutritional resources (46). Variation in α-1,2-fucosyltransferase activity was observed in fucosylated milk proteins, and it is hypothesized that variation not only at the level of secretor status but also at the level of genotype plays an important role in determining which substrates are glycosylated by the same set of enzymes (46). Experimental evidence also points toward a dose effect of FUT2, with significant differences among SeSe and Sese individuals (47).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Colonic mucosa-associated microbiota is influenced by an interaction of Crohn disease and FUT2 ( Secretor ) genotype

Rausch

Rehman

Künzel

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

326

277

View full text Add to dashboard Cite

The FUT2 (Secretor) gene is responsible for the presence of ABO histo-blood group antigens on the gastrointestinal mucosa and in bodily secretions. Individuals lacking a functional copy of FUT2 are known as “nonsecretors” and display an array of differences in susceptibility to infection and disease, including Crohn disease. To determine whether variation in resident microbial communities with respect to FUT2 genotype is a potential factor contributing to susceptibility, we performed 454-based community profiling of the intestinal microbiota in a panel of healthy subjects and Crohn disease patients and determined their genotype for the primary nonsecretor allele in Caucasian populations, W143X (G428A). Consistent with previous studies, we observe significant deviations in the microbial communities of individuals with Crohn disease. Furthermore, the FUT2 genotype explains substantial differences in community composition, diversity, and structure, and we identified several bacterial species displaying disease-by-genotype associations. These findings indicate that alterations in resident microbial communities may in part explain the variety of host susceptibilities surrounding nonsecretor status and that FUT2 is an important genetic factor influencing host–microbial diversity

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Colonic mucosa-associated microbiota is influenced by an interaction of Crohn disease and FUT2 ( Secretor ) genotype

Rausch

Rehman

Künzel

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

326

277

View full text Add to dashboard Cite

show abstract

“…The concentration of both pool and fraction oligosaccharides was 1, 5, and 10 mg/mL. Single purified standards were used at the concentrations found in human milk of the most common genotype mothers (active Secretor and Lewis genes): 2=-FL ϭ 2.5 mg/mL; 3-FL ϭ 0.5 mg/mL; lactodifucotetraose ϭ 0.5 mg/mL; 3=-SL ϭ 0.1 mg/mL 6=-SL ϭ 0.3 mg/mL (6,9,33). At the end of the incubation period, 250 L bacterial inoculum (approx.…”

Section: Methodsmentioning

confidence: 99%

Human Milk Oligosaccharides Inhibit the Adhesion to Caco-2 Cells of Diarrheal Pathogens: Escherichia coli, Vibrio cholerae, and Salmonella fyris

et al. 2006

View full text Add to dashboard Cite

Breast-fed children, compared with the bottle-fed ones, have a lower incidence of acute gastroenteritis due to the presence of several antiinfective factors in human milk. The aim of this work is to study the ability of human milk oligosaccharides to prevent infections related to some common pathogenic bacteria. Oligosaccharides of human milk were fractionated by gel-filtration and characterized by thin-layer chromatography and highperformance anion exchange chromatography. Fractions obtained contained, respectively, 1) acidic oligosaccharides, 2) neutral highmolecular-weight oligosaccharides, and 3) neutral low-molecularweight oligosaccharides. Experiments were carried out to study the ability of oligosaccharides in inhibiting the adhesion of three intestinal microorganisms (enteropathogenic Escherichia coli serotype O119, Vibrio cholerae, and Salmonella fyris) to differentiated Caco-2 cells. The study showed that the acidic fraction had an antiadhesive effect on the all three pathogenic strains studied (with different degrees of inhibition). The neutral high-molecular-weight fraction significantly inhibited the adhesion of E. coli O119 and V. cholerae, but not that of S. fyris; the neutral low-molecular-weight fraction was effective toward E. coli O119 and S. fyris but not V. cholerae. Our results demonstrate that human milk oligosaccharides inhibit the adhesion to epithelial cells not only of common pathogens like E. coli but also for the first time of other aggressive bacteria as V. cholerae and S. fyris. Consequently, oligosaccharides are one of the important defensive factors contained in human milk against acute diarrheal infections of breast-fed infants. (Pediatr Res 59: 377-382, 2006) I nfectious diarrheal diseases constitute a leading cause of infant morbidity not only in developing countries but also in developed areas (1). In fact, in the United States, acute diarrhea represents an important cause of childhood morbidity, especially during the first years of life, determining an economical loss that has been estimated in the order of several millions of dollars (2).In infants, infections of the gastrointestinal tract are caused by a wide variety of enteropathogens, including bacteria, viruses, and parasites. There is now strong evidence supporting a relationship between breast-feeding and a lower incidence in diarrhea. Breast-feeding offers protection with different mechanisms against diarrhea due to several antiinfective substances present in human milk, such as secretory antibodies, lactoferrin, lysozyme, etc. (3-5).In the last 15 y, evidence has also emerged on the protective role of another group of substances, oligosaccharides (6 -8). They are synthesized in a large number by specific glycosyltransferases present in the mammary gland through the sequential addition to lactose of fucose, galactose, Nacetylglucosamine, and sialic acid. Each single oligosaccharide varies dynamically during the different phases of lactation (9). From the quantitative point of view, oligosaccharides, all tog...

show abstract

“…This variability, which may be diurnal and even occur within the same breastfeeding, is also controlled genetically and may depend on the atopic status of the mother (26)(27)(28)(29). To deal with this significant biologic variability, we took two samples from each nursing mother in the study and control groups so that each mother became her own control.…”

Section: Riskin Et Almentioning

confidence: 99%

Changes in immunomodulatory constituents of human milk in response to active infection in the nursing infant

et al. 2011

View full text Add to dashboard Cite

INTRODUCTION:To investigate whether immunologic factors in breast milk change in response to nursing infants' infection. RESULTS: Total cD45 leukocyte count dropped from 5,655 (median and interquartile range: 1,911; 16,871) in the acute phase to 2,122 (672; 6,819) cells/ml milk after recovery with macrophage count decreasing from 1,220 (236; 3,973) to 300 (122; 945) cells/ml. Tumor necrosis factor-α (TNFα) levels decreased from 3.66 ± 1.68 to 2.91 ± 1.51 pg/ml. The decrease in lactoferrin levels was of borderline statistical significance. such differences were not recorded in samples of the controls. Interleukin-10 levels decreased in the sick infants' breast milk after recovery, but also in the healthy controls, requiring further investigation. secretory immunoglobulin a levels did not change significantly in the study or control group. DISCUSSION: During active infection in nursing infants, the total number of white blood cells, specifically the number of macrophages, and TNFα levels increase in their mothers' breast milk. These results may support the dynamic nature of the immune defense provided by breastfeeding sick infants. METHODS: Breast milk from mothers of 31 infants, up to 3 months of age, who were hospitalized with fever, was sampled during active illness and recovery. Milk from mothers of 20 healthy infants served as controls.T he increased sensitivity of the newborn infant to infections originates from the immaturity of the immune system (1). In addition to transfer of immunoglobulin G to the fetus through the placenta, breastfeeding constitutes an important immunological support that the mammalian mother can provide to her relatively immunocompromised offspring against infections during the first months of life (2-6). The immune system in human milk includes secretory immunoglobulin A (sIgA), immunoglobulin G, free fatty acids, monoglycerides, proteins such as lactoferrin, lactalbumin, glycans, nonabsorbed oligosaccharides, exosomes, immunomodulators such as cytokines, nucleic acids, antioxidants, and immune cells such as macrophages, neutrophils, and lymphocytes (1,4,5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). All these immunologic milk constituents interact together and with the newborn's gut directly or indirectly (e.g., by changing the gut flora) to increase immunity against infection, and probably also contribute to the maturation and efficiency of the newborn immune system (5,6).Many studies in both industrialized and developing countries have shown that nursing infants are less vulnerable to infections during their first months of life, including gastroenteritis, respiratory infections, otitis media, urinary tract infections, and necrotizing enterocolitis in premature infants (3,(18)(19)(20)(21)(22)(23)(24)(25).The mechanisms involved in the immunity provided by human milk to the nursing infant are not fully understood. Until recently, it was believed that the changes in immunological constituents of breast milk were mostly related to the time that elapsed from delivery or, in some cases,...

show abstract

Variability of Human Milk Neutral Oligosaccharides in a Diverse Population

Cited by 202 publications

References 42 publications

Colonic mucosa-associated microbiota is influenced by an interaction of Crohn disease and FUT2 ( Secretor ) genotype

Colonic mucosa-associated microbiota is influenced by an interaction of Crohn disease and FUT2 ( Secretor ) genotype

Human Milk Oligosaccharides Inhibit the Adhesion to Caco-2 Cells of Diarrheal Pathogens: Escherichia coli, Vibrio cholerae, and Salmonella fyris

Changes in immunomodulatory constituents of human milk in response to active infection in the nursing infant

Contact Info

Product

Resources

About