Immune Components in Human Milk Are Associated with Early Infant Immunological Health Outcomes: A Prospective Three-Country Analysis

Free amino acids (FAAs) are important regulators of key pathways necessary for growth, development, and immunity. Data on FAAs in human milk (HM) and their roles in infant development are limited. We investigated the levels of FAAs and total amino acids (TAA, i.e., the sum of conjugated amino acids and FAAs) in HM in relation to infant and maternal characteristics and immunological conditions. FAA and TAA levels in HM sampled at 6 weeks (n = 671) and 6 months (n = 441) of lactation were determined using high-performance liquid chromatography. Child growth was ascertained at 4–5 weeks and at 6–7 months of age. Child allergy and lower respiratory tract infections were assessed in the first years of life. Associations of amino acid (AA) levels in HM with child growth and health outcomes were determined by Spearman correlation and modified Poisson regression, respectively. Free glutamine, glutamate, and serine in 6-week HM positively correlated with infant weight gain in the first 4–5 weeks of age. Maternal pre-pregnancy weight and body mass index (BMI) were negatively correlated with free glutamine and asparagine in 6-week and 6-month HM and positively correlated with the sum of TAAs in 6-month HM, but significance was lost following confounder adjustment. Free glutamine was lower in 6-month HM of mothers with an allergy (either active or non-active). No consistent associations were found between FAAs in HM and child health outcomes. However, potential negative associations were observed between specific FAAs and the risk of food allergy. These results suggest that specific FAAs play a role in infant growth. Moreover, these findings warrant further investigations into the relation of FAAs in HM with infant health outcomes and maternal allergy.

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Editorial: Human Milk Composition and Health Outcomes in Children

Frontiers in Pediatrics ◽

10.3389/fped.2019.00319 ◽

2019 ◽

Vol 7 ◽

Cited By ~ 2

Author(s):

Daniel Munblit ◽

Valerie Verhasselt ◽

John O. Warner

Keyword(s):

Health Outcomes ◽

Human Milk ◽

Milk Composition

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Summary on Clinical Aspects of Human Milk on Infant Health Outcomes

Nestlé Nutrition Institute Workshop Series - Human Milk: Composition, Clinical Benefits and Future Opportunities ◽

10.1159/000490485 ◽

2019 ◽

pp. 175-178

Author(s):

Sharon M. Donovan

Keyword(s):

Health Outcomes ◽

Human Milk ◽

Infant Health ◽

Clinical Aspects

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The Infant Gut Microbiota at 12 Months and Its Associations with Maternal Pre-pregnancy BMI, Human Milk Exposure and Infant BMI-for-age Z-score (OR01-05-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz041.or01-05-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Kameron Sugino ◽

Sarah Comstock ◽

Nigel Paneth

Keyword(s):

Child Health ◽

Gut Microbiota ◽

Health Outcomes ◽

Human Milk ◽

Illumina Miseq ◽

Normal Weight ◽

Obese Women ◽

Z Score ◽

Child Health Outcomes ◽

Shannon Diversity

Abstract Objectives Determine if the infant gut microbiota at 12 months of age is associated with maternal pre-pregnancy BMI or infant human milk (HM) exposure. Additionally, determine whether infant BMI z-score at 12 months is associated with the infant microbiota composition and richness at 6 and 12 months. Methods Fecal samples were collected from infants at 6 (n = 35) and 12 (n = 32) months of age. Maternal pre-pregnancy BMI, infant weight and height, and the amount of HM in the infant diet were self-reported. Infant BMI for age z-scores (BAZ) were calculated using WHO Anthro software. Fecal communities were analyzed by 16S rRNA (V4) sequencing on an Illumina Miseq. Results Infants who had HM at 12 months had lower microbiota richness than infants who only received it until 6 months or were not exposed. Microbial community membership (Sorensen) was also significantly different in infants who received any HM at 12 months compared to infants who only received it until 6 months or were not exposed. The 12-month microbiota was similar for infants who received HM until 6 months or had no exposure. Infant BAZ at 12 months positively correlated with maternal pre-pregnancy BMI. Fewer infants born to obese women were exposed to HM at 12 months compared to those born to normal weight women. However, HM exposure at 12 months was not associated with infant BAZ at 12 months. In the 12-month microbiota, Shannon diversity also positively correlated with maternal pre-pregnancy BMI. No alpha or beta diversity metrics of the infant microbiota at 6 months were associated with infant BAZ at 12 months. However, the Shannon diversity of the 12-month microbiota tended to be positively associated the 12-month infant BAZ. Conclusions Maternal pre-pregnancy BMI was associated with higher gut microbiota diversity at 12 months of age. This increase in diversity may influence host metabolism, providing a mechanistic link for elevated BAZ in infants whose mothers had an elevated BMI prior to becoming pregnant. Funding Sources Michigan State AgBioResearch, Child Health Advances through Research with Mothers, Michigan Health Endowment Fund, and the NIH Environmental Influences on Child Health Outcomes (ECHO) Program (Prenatal Exposures and Child Health Outcomes: A Statewide Study (UG3 OD023285)).

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Role of Human Milk Bioactives on Infants' Gut and Immune Health

Frontiers in Immunology ◽

10.3389/fimmu.2021.604080 ◽

2021 ◽

Vol 12 ◽

Author(s):

Laura E. Carr ◽

Misty D. Virmani ◽

Fernanda Rosa ◽

Daniel Munblit ◽

Katelin S. Matazel ◽

...

Keyword(s):

Health Outcomes ◽

Human Milk ◽

Defense Mechanisms ◽

Current Knowledge ◽

Scientific Evidence ◽

Evidence Base ◽

Future Research ◽

Knowledge Gaps ◽

Positive Health ◽

Optimal Health

Exclusive human milk feeding of the newborn is recommended during the first 6 months of life to promote optimal health outcomes during early life and beyond. Human milk contains a variety of bioactive factors such as hormones, cytokines, leukocytes, immunoglobulins, lactoferrin, lysozyme, stem cells, human milk oligosaccharides (HMOs), microbiota, and microRNAs. Recent findings highlighted the potential importance of adding HMOs into infant formula for their roles in enhancing host defense mechanisms in neonates. Therefore, understanding the roles of human milk bioactive factors on immune function is critical to build the scientific evidence base around breastfeeding recommendations, and to enhance positive health outcomes in formula fed infants through modifications to formulas. However, there are still knowledge gaps concerning the roles of different milk components, the interactions between the different components, and the mechanisms behind health outcomes are poorly understood. This review aims to show the current knowledge about HMOs, milk microbiota, immunoglobulins, lactoferrin, and milk microRNAs (miRNAs) and how these could have similar mechanisms of regulating gut and microbiota function. It will also highlight the knowledge gaps for future research.

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Cross-country analysis of correlation between protection of women’s economic and social rights, health improvement and sustainabledevelopment

BMJ Open ◽

10.1136/bmjopen-2017-021350 ◽

2019 ◽

Vol 9 (6) ◽

pp. e021350

Author(s):

Kamiar Alaei ◽

Sedef Akgüngör ◽

Weng-Fong Chao ◽

Sayyida Hasan ◽

Allyson Marshall ◽

...

Keyword(s):

Cluster Analysis ◽

Human Rights ◽

Health Outcomes ◽

Human Development ◽

Women's Rights ◽

Health Improvement ◽

Women’S Rights ◽

Social Rights ◽

Country Analysis ◽

Cross Country

ObjectiveThe goal of this study is to assess the correlation between protection of women’s economic and social rights (WESR), health improvement and sustainable development.MethodsA cross-country analysis of 162 countries was employed to assess development, health and human rights of the countries by measuring associated variables. Data sets for the health, human rights and economic and social rights of these countries were from 2004 to 2010. The dependent variables are health and human development and the independent variables are the human rights variables. Regression analysis and principle axis factoring were used for extraction and varimax method for rotation. Country grouping was made using cluster analysis. Potential biases, resulting from measurement differences in human rights values, were eliminated by using z-transformation to standardise variables.ResultsRegression results reveal that WESR variable is correlated with the health outcomes. Cluster analysis separated the countries into three clusters, based on the WESR variable. Countries where WESR were ‘highly respected’ (44 countries) are categorised into cluster 1; countries where WESR were ‘moderately respected’ (51 countries) are categorised into cluster 2 and countries where WESR were ‘poorly respected’ (63 countries) are categorised into cluster 3. Countries were then compared in their respective clusters based on health and human development variables. It was found that the countries which ‘highly respected’ WESR had better average health values compared with the second and third clusters. Our findings demonstrate that countries with a strong women’s rights status ultimately had better health outcomes.ConclusionWESR status has correlation with the health and human development. When women’s rights are highly respected, the nation is more likely to have higher health averages and accelerated development.

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Hormones in human milk: a summary of the quantity, determinants, and health outcomes of milk hormones

Human Milk ◽

10.1016/b978-0-12-815350-5.00009-7 ◽

2021 ◽

pp. 235-274

Author(s):

Pranati L. Panuganti ◽

Lydia A. Bazzano ◽

Sylvia H. Ley

Keyword(s):

Health Outcomes ◽

Human Milk ◽

Milk Hormones

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Early infant adipose deposition is positively associated with the n-6 to n-3 fatty acid ratio in human milk independent of maternal BMI

International Journal of Obesity ◽

10.1038/ijo.2016.211 ◽

2016 ◽

Vol 41 (4) ◽

pp. 510-517 ◽

Cited By ~ 40

Author(s):

M C Rudolph ◽

B E Young ◽

D J Lemas ◽

C E Palmer ◽

T L Hernandez ◽

...

Keyword(s):

Fatty Acid ◽

Human Milk ◽

Fatty Acid Ratio ◽

Early Infant ◽

Acid Ratio ◽

Maternal Bmi

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Untargeted Metabolomic Analysis of Gestationally Matched Human and Bovine Milk Samples at 2-Weeks Postnatal

Current Developments in Nutrition ◽

10.1093/cdn/nzaa054_097 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1025-1025

Author(s):

Dominick Lemas ◽

Xinsong Du ◽

Bethany Dado-Senn ◽

Marina Magalhães ◽

Larissa Iapicca ◽

...

Keyword(s):

Health Outcomes ◽

Human Milk ◽

Infant Health ◽

High Resolution Mass Spectrometry ◽

Bovine Milk ◽

Normal Weight ◽

Untargeted Metabolomics ◽

Human Breast Milk ◽

Metabolomic Analysis ◽

Milk Samples

Abstract Objectives Human breast milk is the ideal nutrition source for infant development during the first year of life. Epidemiological data demonstrates that bovine whole milk is often substituted for human milk during the first 12-months of life and may be associated with adverse infant outcomes. The goal of this project is to interrogate the human and bovine milk metabolome at 2-weeks postnatal to identify unique and overlapping metabolites that may impact infant health outcomes. Methods Human milk (n = 10) was collected at 2-weeks postpartum from normal weight mothers (pre-pregnant BMI <25 kg/m2) that vaginally delivered term infants and planned to exclusively breastfeed for at least 2-months. Similarly, bovine milk (n = 10) was collected 2-weeks postpartum from normal weight primiparous Holstein dairy cows. Dairy cattle were housed in sand-bedded, shaded barns with access to fans and water soakers and fed a common transition cow total mixed ration. Untargeted metabolomics was completed on all milk samples using high-resolution mass spectrometry. Metabolomic analysis was implemented using an open-source containerized metabolomics pipeline. Data processing was completed using MZmine, mummichog and Python were used for statistical analysis. Results We detected 716 metabolomic features in human and bovine milk samples after quality control. Our analysis also revealed that 43% (312) of metabolomics features were present in both human and bovine milk, 23% (167) of metabolomics features were unique to human milk and 33% (237) of metabolomics features existed only in bovine milk samples. Pathway analysis revealed that sialic acid and glycosphingolipid metabolism (P < 0.0009) were common to human and bovine milk samples. We also found that amino acid (tryptophan, tyrosine, purine) metabolism (P < 0.005) was unique to bovine samples and vitamin B3 pathways (P = 0.03) was unique to human samples. Conclusions Our analysis revealed a core milk metabolome shared between human and bovine samples. Collectively, these results highlight untargeted metabolomics as a potential strategy to identify unique and overlapping metabolites in bovine and human milk that may impact infant health outcomes. Funding Sources Research was supported by NIDDK/K01; SECIM P&F; CTSI Pilot Award; Robin Hood Foundation; NIH Loan Repayment Program.

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