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Unraveling the Structural and Functional Complexity of Human Milk by...
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Unraveling the Structural and Functional Complexity of Human Milk by Metabolomics and Lipidomics

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Food Metabolomics".

Deadline for manuscript submissions: closed (15 September 2023) | Viewed by 12956

Special Issue Editors

Dr. Weronika Hewelt-Belka

E-Mail Website
Guest Editor
Department of Analytical Chemistry, Faculty of Chemistry, Gdańsk University of Technology, Gabriela Narutowicza 11/12, 80-233 Gdańsk, Poland
Interests: lipidomics; metabolomics; high-performance liquid chromatography; sample preparation; mass spectrometry; metabolite identification; extracellular vesicle lipids
Dr. Ulrik Kræmer Sundekilde

E-Mail Website
Guest Editor
Department of Food Science, Faculty of Technical Sciences, Aarhus University, Agro Food Park 48, DK-8200 Aarhus, Denmark
Interests: metabolomics; proteomics; glycomics; human milk; infant metabolism; microbiome; multivariate data analysis; nuclear magnetic resonance spectroscopy
Special Issues, Collections and Topics in MDPI journals
Dr. Dorota Garwolińska

E-Mail Website
Guest Editor
Department of Analytical Chemistry, Faculty of Chemistry, Gdańsk University of Technology, Gabriela Narutowicza 11/12, 80-233 Gdańsk, Poland
Interests: lipidomics; metabolomics; mass spectrometry; high-performance liquid chromatography; metabolite identification; sample preparation; human milk

Special Issue Information

Dear Colleagues,

Metabolomics and lipidomics are powerful tools enabling in-depth insight into the metabolites and lipid composition of biological systems. In recent years, both metabolomics and lipidomics have been applied to human milk analysis, unravelling the real complexity of this biofluid. Human milk is considered a gold standard in the nutrition of newborns, and not without a reason. It is composed of an enormous number of types of biomolecules, including hundreds of distinct species of lipids. Moreover, the composition of human milk is dynamic and changes inter- and intraindividual. Employment of omics approaches in human milk research expands the knowledge about the composition and dynamic nature of the human milk metabolome and lipidome. Available methods use sophisticated technical solutions both at the level of sample preparation and final analysis; however, they are not free of analytical obstacles. This Special Issue will focus on the “gold standards” and new solutions in metabolomics and lipidomics of human milk, including each step of the analytical workflow: sample collection and storage, metabolite/lipid extraction, separation and detection, identification and data analysis. Articles presenting the results of studies employing “omic” approaches are also welcomed.

Dr. Weronika Hewelt-Belka
Dr. Ulrik Kræmer Sundekilde
Dr. Dorota Garwolińska
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • human milk metabolomics
  • human milk lipidomics
  • human milk metabolites
  • human milk lipids
  • metabolite extraction
  • lipid extraction

Published Papers (5 papers)

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Research

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18 pages, 3600 KiB  
Article
The Protective Role of Exosome-Derived MicroRNAs and Proteins from Human Breast Milk against Infectious Agents
by Ki-Uk Kim, Kyusun Han, Jisu Kim, Da Hyeon Kwon, Yong Woo Ji, Dae Yong Yi and Hyeyoung Min
Metabolites 2023, 13(5), 635; https://doi.org/10.3390/metabo13050635 - 8 May 2023
Cited by 3 | Viewed by 1989
Abstract
Human breast milk (HBM)-derived exosomes contain various biological and immunological components. However, comprehensive immune-related and antimicrobial factor analysis requires transcriptomic, proteomic, and multiple databases for functional analyses, and has yet to be conducted. Therefore, we isolated and confirmed HBM-derived exosomes by detecting specific [...] Read more.
Human breast milk (HBM)-derived exosomes contain various biological and immunological components. However, comprehensive immune-related and antimicrobial factor analysis requires transcriptomic, proteomic, and multiple databases for functional analyses, and has yet to be conducted. Therefore, we isolated and confirmed HBM-derived exosomes by detecting specific markers and examining their morphology using western blot and transmission electron microscopy. Moreover, we implemented small RNA sequencing and liquid chromatography-mass spectrometry to investigate substances within the HBM-derived exosomes and their roles in combating pathogenic effects, identifying 208 miRNAs and 377 proteins associated with immunological pathways and diseases. Integrated omics analyses identified a connection between the exosomal substances and microbial infections. In addition, gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathway analyses demonstrated that HBM-derived exosomal miRNA and proteins influence immune-related functions and pathogenic infections. Finally, protein–protein interaction analysis identified three primary proteins (ICAM1, TLR2, and FN1) associated with microbial infections mediating pro-inflammation, controlling infection, and facilitating microbial elimination. Our findings determine that HBM-derived exosomes modulate the immune system and could offer therapeutic strategies for regulating pathogenic microbial infection. Full article
(This article belongs to the Special Issue Unraveling the Structural and Functional Complexity of Human Milk by Metabolomics and Lipidomics)
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18 pages, 3095 KiB  
Article
Impact of Cesarean Delivery and Breastfeeding on Secretory Immunoglobulin A in the Infant Gut Is Mediated by Gut Microbiota and Metabolites
by Yuan Yao Chen, Hein M. Tun, Catherine J. Field, Piushkumar J. Mandhane, Theo J. Moraes, Elinor Simons, Stuart E. Turvey, Padmaja Subbarao, James A. Scott and Anita L. Kozyrskyj
Metabolites 2023, 13(2), 148; https://doi.org/10.3390/metabo13020148 - 18 Jan 2023
Cited by 2 | Viewed by 2299
Abstract
How gut immunity in early life is shaped by birth in relation to delivery mode, intrapartum antibiotic prophylaxis (IAP) and labor remains undetermined. We aimed to address this gap with a study of secretory Immunoglobulin A (SIgA) in the infant gut that also [...] Read more.
How gut immunity in early life is shaped by birth in relation to delivery mode, intrapartum antibiotic prophylaxis (IAP) and labor remains undetermined. We aimed to address this gap with a study of secretory Immunoglobulin A (SIgA) in the infant gut that also tested SIgA-stimulating pathways mediated by gut microbiota and metabolites. Among 1017 Canadian full-term infants, gut microbiota of fecal samples collected at 3 and 12 months were profiled using 16S rRNA sequencing; C. difficile was quantified by qPCR; fecal metabolites and SIgA levels were measured by NMR and SIgA enzyme-linked immunosorbent assay, respectively. We assessed the putative causal relationships from birth events to gut microbiota and metabolites, and ultimately to SIgA, in statistical sequential mediation models, adjusted for maternal gravida status in 551 infants. As birth mode influences the ability to breastfeed, the statistical mediating role of breastfeeding status and milk metabolites was also evaluated. Relative to vaginal birth without maternal IAP, cesarean section (CS) after labor was associated with reduced infant gut SIgA levels at 3 months (6.27 vs. 4.85 mg/g feces, p < 0.05); this association was sequentially mediated through gut microbiota and metabolites of microbial or milk origin. Mediating gut microbiota included Enterobacteriaceae, C. difficile, and Streptococcus. The milk or microbial metabolites in CS-SIgA mediating pathways were galactose, fucose, GABA, choline, lactate, pyruvate and 1,2-propanediol. This cohort study documented the impact of birth on infant gut mucosal SIgA. It is the first to characterize gut microbe-metabolite mediated pathways for early-life SIgA maturation, pathways that require experimental verification. Full article
(This article belongs to the Special Issue Unraveling the Structural and Functional Complexity of Human Milk by Metabolomics and Lipidomics)
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11 pages, 949 KiB  
Article
Changes in microRNAs during Storage and Processing of Breast Milk
by Jun Hwan Kim, Ki-Uk Kim, Hyeyoung Min, Eun Sun Lee, In Seok Lim, Jeonglyn Song, Insoo Kang and Dae Yong Yi
Metabolites 2023, 13(2), 139; https://doi.org/10.3390/metabo13020139 - 17 Jan 2023
Cited by 1 | Viewed by 1676
Abstract
Human breast milk (HBM) is the ideal source of nutrients for infants and is rich in microRNA (miRNA). In recent years, expressed breast milk feeding rather than direct breastfeeding has become increasingly prevalent for various reasons. Expressed HBM requires storage and processing, which [...] Read more.
Human breast milk (HBM) is the ideal source of nutrients for infants and is rich in microRNA (miRNA). In recent years, expressed breast milk feeding rather than direct breastfeeding has become increasingly prevalent for various reasons. Expressed HBM requires storage and processing, which can cause various changes in the ingredients. We investigated how the miRNAs in HBM change due to processes often used in real life. HBM samples collected from 10 participants were each divided into seven groups according to the storage temperature, thawing method, and storage period. In addition, we analyzed the miRNA changes in each group. The number of microRNAs that showed significant expression was not large compared to the thousands of miRNAs contained in breast milk. Therefore, it is difficult to suggest that the various storage and thawing processes have a great influence on the overall expression of miRNA. However, a short-term refrigeration storage method revealed little change in nutrients compared to other storage and thawing methods. Taking all factors into consideration, short-term refrigeration is recommended to minimize changes in the composition or function of breast milk. Full article
(This article belongs to the Special Issue Unraveling the Structural and Functional Complexity of Human Milk by Metabolomics and Lipidomics)
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13 pages, 11635 KiB  
Article
Human Milk from Tandem Feeding Dyads Does Not Differ in Metabolite and Metataxonomic Features When Compared to Single Nursling Dyads under Six Months of Age
by Natalie S. Shenker, Alvaro Perdones-Montero, Adam Burke, Sarah Stickland, Julie A. K. McDonald and Simon J. S. Cameron
Metabolites 2022, 12(11), 1069; https://doi.org/10.3390/metabo12111069 - 4 Nov 2022
Viewed by 3292
Abstract
Given the long-term advantages of exclusive breastfeeding to infants and their mothers, there is both an individual and public health benefit to its promotion and support. Data on the composition of human milk over the course of a full period of lactation for [...] Read more.
Given the long-term advantages of exclusive breastfeeding to infants and their mothers, there is both an individual and public health benefit to its promotion and support. Data on the composition of human milk over the course of a full period of lactation for a single nursling is sparse, but data on human milk composition during tandem feeding (feeding children of different ages from different pregnancies) is almost entirely absent. This leaves an important knowledge gap that potentially endangers the ability of parents to make a fully informed choice on infant feeding. We compared the metataxonomic and metabolite fingerprints of human milk samples from 15 tandem feeding dyads to that collected from ten exclusively breastfeeding single nursling dyads where the nursling is under six months of age. Uniquely, our cohort also included three tandem feeding nursling dyads where each child showed a preferential side for feeding—allowing a direct comparison between human milk compositions for different aged nurslings. Across our analysis of volume, total fat, estimation of total microbial load, metabolite fingerprinting, and metataxonomics, we showed no statistically significant differences between tandem feeding and single nursling dyads. This included comparisons of preferential side nurslings of different ages. Together, our findings support the practice of tandem feeding of nurslings, even when feeding an infant under six months. Full article
(This article belongs to the Special Issue Unraveling the Structural and Functional Complexity of Human Milk by Metabolomics and Lipidomics)
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Review

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13 pages, 726 KiB  
Review
Human Milk Lipids and Small Metabolites: Maternal and Microbial Origins
by Lisa F. Stinson and Alexandra D. George
Metabolites 2023, 13(3), 422; https://doi.org/10.3390/metabo13030422 - 13 Mar 2023
Cited by 6 | Viewed by 2661
Abstract
Although there has been limited application in the field to date, human milk omics research continues to gain traction. Human milk lipidomics and metabolomics research is particularly important, given the significance of milk lipids and metabolites for infant health. For researchers conducting compositional [...] Read more.
Although there has been limited application in the field to date, human milk omics research continues to gain traction. Human milk lipidomics and metabolomics research is particularly important, given the significance of milk lipids and metabolites for infant health. For researchers conducting compositional milk analyses, it is important to consider the origins of these compounds. The current review aims to provide a summary of the existing evidence on the sources of human milk lipids and small metabolites. Here, we describe five major sources of milk lipids and metabolites: de novo synthesis from mammary cells, production by the milk microbiota, dietary consumption, release from non-mammary tissue, and production by the gut microbiota. We synthesize the literature to provide evidence and understanding of these pathways in the context of mammary gland biology. We recommend future research focus areas to elucidate milk lipid and small metabolite synthesis and transport pathways. Better understanding of the origins of human milk lipids and metabolites is important to improve translation of milk omics research, particularly regarding the modulation of these important milk components to improve infant health outcomes. Full article
(This article belongs to the Special Issue Unraveling the Structural and Functional Complexity of Human Milk by Metabolomics and Lipidomics)
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