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Journal ArticleDOI

What’s normal? Oligosaccharide concentrations and profiles in milk produced by healthy women vary geographically

TL;DR: The hypothesis that normal HMO concentrations and profiles vary geographically, even in healthy women is supported and targeted genomic analyses are required to determine whether these differences are due at least in part to genetic variation.
About: This article is published in The American Journal of Clinical Nutrition.The article was published on 2017-05-01 and is currently open access. It has received 263 citations till now. The article focuses on the topics: Postpartum period.
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Journal ArticleDOI
TL;DR: The infant microbiota, the mechanisms that drive its establishment and composition, and how microbial consortia may be molded by natural or artificial interventions are described and the relevance of key microbial players of the infant gut microbiota, in particular bifidobacteria, with respect to their role in health and disease are discussed.
Abstract: The human gut microbiota is engaged in multiple interactions affecting host health during the host's entire life span. Microbes colonize the neonatal gut immediately following birth. The establishment and interactive development of this early gut microbiota are believed to be (at least partially) driven and modulated by specific compounds present in human milk. It has been shown that certain genomes of infant gut commensals, in particular those of bifidobacterial species, are genetically adapted to utilize specific glycans of this human secretory fluid, thus representing a very intriguing example of host-microbe coevolution, where both partners are believed to benefit. In recent years, various metagenomic studies have tried to dissect the composition and functionality of the infant gut microbiome and to explore the distribution across the different ecological niches of the infant gut biogeography of the corresponding microbial consortia, including those corresponding to bacteria and viruses, in healthy and ill subjects. Such analyses have linked certain features of the microbiota/microbiome, such as reduced diversity or aberrant composition, to intestinal illnesses in infants or disease states that are manifested at later stages of life, including asthma, inflammatory bowel disease, and metabolic disorders. Thus, a growing number of studies have reported on how the early human gut microbiota composition/development may affect risk factors related to adult health conditions. This concept has fueled the development of strategies to shape the infant microbiota composition based on various functional food products. In this review, we describe the infant microbiota, the mechanisms that drive its establishment and composition, and how microbial consortia may be molded by natural or artificial interventions. Finally, we discuss the relevance of key microbial players of the infant gut microbiota, in particular bifidobacteria, with respect to their role in health and disease.

970 citations


Cites background from "What’s normal? Oligosaccharide conc..."

  • ...HMO composition produced by healthy women varies geographically (218)....

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Journal ArticleDOI
TL;DR: Providing pumped breastmilk was consistently associated with multiple microbiota parameters including enrichment of potential pathogens and depletion of bifidobacteria, which support the retrograde inoculation hypothesis, whereby the infant oral cavity impacts the milk microbiota.

297 citations


Cites background or result from "What’s normal? Oligosaccharide conc..."

  • ..., 2011) as well as the macro- and micro-nutrient profile of human milk (Mazurier et al., 2017; McGuire et al., 2017), altering the niche for milk microbiota....

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  • ...Two main pathways have been proposed to explain the origin of milk microbiota: entero-mammary translocation of the maternal gut microbiota and retrograde inoculation by the infant’s oral microbiota (McGuire and McGuire, 2017)....

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  • ...Dominant milk bacteria in our cohort were in accordance with previously published results (McGuire and McGuire, 2017)....

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Journal ArticleDOI
TL;DR: There was an unexpected persistence of immunoglobulin G almost until weaning, potentially indicating prolonged trans-intestinal transfer of IgG and among components of innate immune protection were found fucosyllactose and siallylactose that are thought to impede colonisation by pathogens and encourage an appropriate milk-digestive and protective gut microbiome.
Abstract: True seals have the shortest lactation periods of any group of placental mammal. Most are capital breeders that undergo short, intense lactations, during which they fast while transferring substantial proportions of their body reserves to their pups, which they then abruptly wean. Milk was collected from Atlantic grey seals (Halichoerus grypus) periodically from birth until near weaning. Milk protein profiles matured within 24 hours or less, indicating the most rapid transition from colostrum to mature phase lactation yet observed. There was an unexpected persistence of immunoglobulin G almost until weaning, potentially indicating prolonged trans-intestinal transfer of IgG. Among components of innate immune protection were found fucosyllactose and siallylactose that are thought to impede colonisation by pathogens and encourage an appropriate milk-digestive and protective gut microbiome. These oligosaccharides decreased from early lactation to almost undetectable levels by weaning. Taurine levels were initially high, then fell, possibly indicative of taurine dependency in seals, and progressive depletion of maternal reserves. Metabolites that signal changes in the mother’s metabolism of fats, such as nicotinamide and derivatives, rose from virtual absence, and acetylcarnitines fell. It is therefore possible that indicators of maternal metabolic strain exist that signal the imminence of weaning.

237 citations

Journal ArticleDOI
TL;DR: The limited clinical data suggest that the addition of HMOs to infant formula seems to be safe and well tolerated, inducing a normal growth and suggesting a trend towards health benefits.
Abstract: The authors reviewed the published evidence on the presence of oligosaccharides in human milk (HMO) and their benefits in in vitro and in vivo studies. The still limited data of trials evaluating the effect of mainly 2′-fucosyllactose (2′-FL) on the addition of some of HMOs to infant formula were also reviewed. PubMed was searched from January 1990 to April 2018. The amount of HMOs in mother’s milk is a dynamic process as it changes over time. Many factors, such as duration of lactation, environmental, and genetic factors, influence the amount of HMOs. HMOs may support immune function development and provide protection against infectious diseases directly through the interaction of the gut epithelial cells or indirectly through the modulation of the gut microbiota, including the stimulation of the bifidobacteria. The limited clinical data suggest that the addition of HMOs to infant formula seems to be safe and well tolerated, inducing a normal growth and suggesting a trend towards health benefits. HMOs are one of the major differences between cow’s milk and human milk, and available evidence indicates that these components do have a health promoting benefit. The addition of one or two of these components to infant formula is safe, and brings infant formula closer to human milk. More prospective, randomized trials in infants are need to evaluate the clinical benefit of supplementing infant formula with HMOs.

179 citations


Cites background from "What’s normal? Oligosaccharide conc..."

  • ...A recent study showed that HMO content and profiles vary geographically, even when secretor and Lewis blood group genes were considered [20,28]....

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Journal ArticleDOI
TL;DR: HMO concentrations vary widely between mothers and are associated with multiple characteristics beyond genetic Secretor status, as well as feeding practices and environmental factors, which are warranted to determine how these associations affect infant health.
Abstract: Background Human milk oligosaccharides (HMOs) shape the developing gut microbiome and influence immune function. Aside from genetic Secretor status, the factors influencing HMO synthesis and secretion are largely unknown. Objective We aimed to identify modifiable and nonmodifiable factors associated with HMO concentrations. Methods This prospective observational study included a representative subset of 427 mothers participating in the CHILD birth cohort (mean age: 33 y, 73% Caucasian). Breast milk was collected at 3-4 mo postpartum. Concentrations of 19 predominant HMOs were measured by rapid high-throughput HPLC. Secretor status was defined by the presence of 2'-fucosylactose. Associations with maternal, infant, and environmental factors were explored using multivariable regression. Breastfeeding duration was explored as a secondary outcome. Results Overall, 72% of mothers were Secretors and the mean ± SD duration of any breastfeeding was 12.8 ± 5.7 mo. HMO profiles were highly variable; total HMO concentrations varied 3.7-fold and individual HMOs varied 20- to >100-fold. Secretor mothers had higher total HMO concentrations than did non-Secretors (mean: 15.91 ± 2.80 compared with 8.94 ± 1.51 μmol/mL, P < 0.001) and all individual HMOs differed by Secretor status, except for disialyllacto-N-tetraose (DSLNT). Most HMO concentrations were lower in milk collected later in lactation, although some were higher including DSLNT and 3'-sialyllactose. Independent of Secretor status and lactation stage, seasonal and geographic variation was observed for several HMOs. Parity, ethnicity, and breastfeeding exclusivity also emerged as independent factors associated with some HMOs, whereas diet quality and mode of delivery did not. Together, these factors explained between 14% (for 6'-sialyllactose) and 92% (for 2'-fucosyllactose) of the observed variation in HMO concentrations. Lower concentrations of lacto-N-hexaose or fucodisialyllacto-N-hexaose were associated with earlier breastfeeding cessation. Conclusions HMO concentrations vary widely between mothers and are associated with multiple characteristics beyond genetic Secretor status, as well as feeding practices and environmental factors. Further research is warranted to determine how these associations affect infant health. This study was registered at clinicaltrials.gov as NCT03225534.

153 citations

References
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Journal Article
TL;DR: Copyright (©) 1999–2012 R Foundation for Statistical Computing; permission is granted to make and distribute verbatim copies of this manual provided the copyright notice and permission notice are preserved on all copies.
Abstract: Copyright (©) 1999–2012 R Foundation for Statistical Computing. Permission is granted to make and distribute verbatim copies of this manual provided the copyright notice and this permission notice are preserved on all copies. Permission is granted to copy and distribute modified versions of this manual under the conditions for verbatim copying, provided that the entire resulting derived work is distributed under the terms of a permission notice identical to this one. Permission is granted to copy and distribute translations of this manual into another language, under the above conditions for modified versions, except that this permission notice may be stated in a translation approved by the R Core Team.

272,030 citations

Journal ArticleDOI
TL;DR: In this paper, a different approach to problems of multiple significance testing is presented, which calls for controlling the expected proportion of falsely rejected hypotheses -the false discovery rate, which is equivalent to the FWER when all hypotheses are true but is smaller otherwise.
Abstract: SUMMARY The common approach to the multiplicity problem calls for controlling the familywise error rate (FWER). This approach, though, has faults, and we point out a few. A different approach to problems of multiple significance testing is presented. It calls for controlling the expected proportion of falsely rejected hypotheses -the false discovery rate. This error rate is equivalent to the FWER when all hypotheses are true but is smaller otherwise. Therefore, in problems where the control of the false discovery rate rather than that of the FWER is desired, there is potential for a gain in power. A simple sequential Bonferronitype procedure is proved to control the false discovery rate for independent test statistics, and a simulation study shows that the gain in power is substantial. The use of the new procedure and the appropriateness of the criterion are illustrated with examples.

83,420 citations


"What’s normal? Oligosaccharide conc..." refers methods in this paper

  • ...Differences in proportions of each cohort that were characterized as being secretors were tested with the use of a chi-square post hoc procedure in the NCStats package (36) with Benjamini and Hochberg falsediscovery-rate corrections (37)....

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Book
13 Aug 2009
TL;DR: This book describes ggplot2, a new data visualization package for R that uses the insights from Leland Wilkisons Grammar of Graphics to create a powerful and flexible system for creating data graphics.
Abstract: This book describes ggplot2, a new data visualization package for R that uses the insights from Leland Wilkisons Grammar of Graphics to create a powerful and flexible system for creating data graphics. With ggplot2, its easy to: produce handsome, publication-quality plots, with automatic legends created from the plot specification superpose multiple layers (points, lines, maps, tiles, box plots to name a few) from different data sources, with automatically adjusted common scales add customisable smoothers that use the powerful modelling capabilities of R, such as loess, linear models, generalised additive models and robust regression save any ggplot2 plot (or part thereof) for later modification or reuse create custom themes that capture in-house or journal style requirements, and that can easily be applied to multiple plots approach your graph from a visual perspective, thinking about how each component of the data is represented on the final plot. This book will be useful to everyone who has struggled with displaying their data in an informative and attractive way. You will need some basic knowledge of R (i.e. you should be able to get your data into R), but ggplot2 is a mini-language specifically tailored for producing graphics, and youll learn everything you need in the book. After reading this book youll be able to produce graphics customized precisely for your problems,and youll find it easy to get graphics out of your head and on to the screen or page.

29,504 citations


"What’s normal? Oligosaccharide conc..." refers methods in this paper

  • ...Multivariate analyses to explore patterns and similarities in complex HMO profiles were followed and included nonmetric multidimensional scaling analyses with the use of a Bray-Curtis dissimilarity matrix [metaMDS procedure in the vegan package (38) and ggplot2 package (40) and a principle components analysis princomp procedure in the stats base package of R software]....

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01 Jan 2015

2,632 citations


"What’s normal? Oligosaccharide conc..." refers methods in this paper

  • ...To account for the multivariate nature of the data, the NMF method was considered (43)....

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  • ...2 procedure in the gplots package (43) to look for patterns within the data structure (distinct from the correlation maps and shown in Supplemental Figures 1 and 2)....

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Journal ArticleDOI
TL;DR: Nonnegative matrix factorization is described, an algorithm based on decomposition by parts that can reduce the dimension of expression data from thousands of genes to a handful of metagenes, and found less sensitive to a priori selection of genes or initial conditions and able to detect alternative or context-dependent patterns of gene expression in complex biological systems.
Abstract: We describe here the use of nonnegative matrix factorization (NMF), an algorithm based on decomposition by parts that can reduce the dimension of expression data from thousands of genes to a handful of metagenes. Coupled with a model selection mechanism, adapted to work for any stochastic clustering algorithm, NMF is an efficient method for identification of distinct molecular patterns and provides a powerful method for class discovery. We demonstrate the ability of NMF to recover meaningful biological information from cancer-related microarray data. NMF appears to have advantages over other methods such as hierarchical clustering or self-organizing maps. We found it less sensitive to a priori selection of genes or initial conditions and able to detect alternative or context-dependent patterns of gene expression in complex biological systems. This ability, similar to semantic polysemy in text, provides a general method for robust molecular pattern discovery.

1,818 citations


"What’s normal? Oligosaccharide conc..." refers methods in this paper

  • ...In this set of analyses, data were processed with the use of the Brunet method (42), and 6 basis components were retained on the basis of the rank estimate that was determined from the same package....

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