Examining the relationship between maternal body size, gestational glucose tolerance status, mode of delivery and ethnicity on mother’s milk microbiota at three months post-partum

Abstract Background: Few studies have examined how maternal body mass index (BMI), mode of delivery and ethnicity affect the microbial composition of human milk and none have examined associations with maternal metabolic status. Given the high prevalence of maternal adiposity and impaired glucose metabolism, and the importance of human milk in the colonization of the infant gut, we systematically investigated the associations between these maternal factors and milk microbial composition and functionality. Methods: Women ≥20 years were recruited during pregnancy and milk samples were collected at 3 months post-partum (NCT01405547). Demographic data, weight, height, and a 3-hour oral glucose tolerance test were conducted at 30 (95% CI: 25-33) weeks gestation. Metagenomic DNA extraction and 16S ribosomal RNA gene sequencing of the V4 hypervariable region (Illumina MiSeq) was carried out on 113 milk samples. Results: Multivariable linear regression analyses demonstrated no significant associations between maternal characteristics (maternal BMI [pre-pregnancy, 3 months post-partum], glucose tolerance, mode of delivery and ethnicity) and microbiota alpha-diversity; however, pre-pregnancy BMI was associated with human milk beta-diversity (Bray-Curtis p=0.040). Women with a pre-pregnancy BMI >30 kg/m2 (obese) had a greater incidence of Bacteroidetes (incidence rate ratio [IRR]: 3.70 [95% CI: 1.61-8.48]) and a reduced incidence of Proteobacteria (0.62 [0.43-0.90]), compared to overweight women (BMI 25.0-29.9 kg/m2) as assessed by multivariable Poisson regression. Increased incidence of Gemella was observed among overweight (versus healthy) mothers with gestational diabetes (5.96 [1.85-19.21]) and obese (versus healthy) mothers with impaired glucose tolerance (4.04 [1.63-10.01]). An increased incidence of Brevundimonas (16.70 [5.99-46.57]) was found in the milk of women who underwent an unscheduled C-section versus vaginal delivery. Lastly, functional gene inference demonstrated that obesity was associated with increased abundance of genes encoding for the biosynthesis of secondary metabolites in milk (coefficient=0.00028, p=0.0070). Conclusions: Mother’s milk has a diverse microbiota of which its diversity and differential abundance appear associated with maternal body size, glucose tolerance status, mode of delivery, and ethnicity. Further research is warranted to determine whether this variability in the milk microbiota impacts colonization of the infant gut.

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Examining the relationship between maternal body size, gestational glucose tolerance status, mode of delivery and ethnicity on human milk microbiota at three months post-partum

BMC Microbiology ◽

10.1186/s12866-020-01901-9 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Lauren LeMay-Nedjelski ◽

James Butcher ◽

Sylvia H. Ley ◽

Michelle R. Asbury ◽

Anthony J. Hanley ◽

...

Keyword(s):

Body Size ◽

Glucose Tolerance ◽

Human Milk ◽

Post Partum ◽

Mode Of Delivery ◽

Maternal Body ◽

Glucose Tolerance Status ◽

The Relationship

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Longitudinal Changes in the Concentration of Major Human Milk Proteins in the First Six Months of Lactation and Their Effects on Infant Growth

Nutrients ◽

10.3390/nu13051476 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1476

Author(s):

Jian Zhang ◽

Ai Zhao ◽

Shiyun Lai ◽

Qingbin Yuan ◽

Xiaojiang Jia ◽

...

Keyword(s):

Human Milk ◽

Maternal Education ◽

Mode Of Delivery ◽

Milk Proteins ◽

Protein Composition ◽

Infant Growth ◽

Term Infants ◽

Longitudinal Changes ◽

Milk Samples ◽

The Impact

Our knowledge related to human milk proteins is still limited. The present study determined the changes in multiple human milk proteins during the first six months of lactation, investigated the influencing factors of milk proteins, and explored the impact of milk proteins on infant growth. A total of 105 lactating women and their full-term infants from China were prospectively surveyed in this research. Milk samples were collected at 1–5 days, 8–14 days, 1 month, and 6 months postpartum. Concentrations of total protein and α-lactalbumin were measured in all milk samples, and concentrations of lactoferrin, osteopontin, total casein, β-casein, αs−1 casein, and κ-casein were measured in milk from 51 individuals using ultra performance liquid chromatography coupled with mass spectrometry. The concentration of measured proteins in the milk decreased during the first six months of postpartum (p-trend < 0.001). Maternal age, mode of delivery, maternal education, and income impacted the longitudinal changes in milk proteins (p-interaction < 0.05). Concentrations of αs−1 casein in milk were inversely associated with the weight-for-age Z-scores of the infants (1 m: r −0.29, p 0.038; 6 m: r −0.33, p 0.020). In conclusion, the concentration of proteins in milk decreased over the first six months postpartum, potentially influenced by maternal demographic and delivery factors. Milk protein composition may influence infant weights.

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Sex Differences in Insulin Levels in Older Adults and the Effect of Body Size, Estrogen Replacement Therapy, and Glucose Tolerance Status: The Rancho Bernardo Study, 1984-1987

Diabetes Care ◽

10.2337/diacare.18.2.220 ◽

1995 ◽

Vol 18 (2) ◽

pp. 220-225 ◽

Cited By ~ 20

Author(s):

A. Ferrara ◽

E. Barrett-Connor ◽

D. L. Wingard ◽

S. L. Edelstein

Keyword(s):

Older Adults ◽

Sex Differences ◽

Body Size ◽

Glucose Tolerance ◽

Replacement Therapy ◽

Estrogen Replacement Therapy ◽

Estrogen Replacement ◽

Insulin Levels ◽

Glucose Tolerance Status

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Maternal Microbiota, Cortisol Concentration, and Post-Partum Weight Recovery Are Dependent on Mode of Delivery

Nutrients ◽

10.3390/nu12061779 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1779

Author(s):

Marta Selma-Royo ◽

Izaskun García-Mantrana ◽

Marta Calatayud ◽

Anna Parra-Llorca ◽

Cecilia Martínez-Costa ◽

...

Keyword(s):

Vaginal Delivery ◽

Salivary Cortisol ◽

Post Partum ◽

Mode Of Delivery ◽

Cortisol Concentration ◽

Intestinal Microbiome ◽

Rrna Gene ◽

Retention Data ◽

Weight Retention ◽

Microbial Composition

The importance of the maternal microbiota in terms of the initial bacterial seeding has previously been highlighted; however, little is currently known about the perinatal factors that could affect it. The aim of this study was to evaluate the effects of various delivery-related factors on the intestinal microbiome at delivery time and on post-partum weight retention. Data were collected from mothers (n = 167) during the first four months post-partum. A subset of 100 mothers were selected for the determination of the salivary cortisol concentration and microbiome composition at birth by 16S rRNA gene sequencing. The maternal microbiota was classified into two distinct clusters with significant differences in microbial composition and diversity. Maternal microbiota was also significantly influenced by the mode of delivery. Moreover, the salivary cortisol concentration was associated with some maternal microbiota genera and it was significantly higher in the vaginal delivery group (p = 0.003). The vaginal delivery group exhibited lower post-partum weight retention than the C-section (CS) mothers at four months post-partum (p < 0.001). These results support the hypothesis that the mode of delivery as well as the codominant hormonal changes could influence the maternal microbiota and possibly impact maternal weight recovery during the post-partum period.

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Impact of Glucose Tolerance Status, Sex, and Body Size on Glucose Absorption Patterns During OGTTs

Diabetes Care ◽

10.2337/dc13-0592 ◽

2013 ◽

Vol 36 (11) ◽

pp. 3691-3697 ◽

Cited By ~ 18

Author(s):

K. Faerch ◽

G. Pacini ◽

J. J. Nolan ◽

T. Hansen ◽

A. Tura ◽

...

Keyword(s):

Body Size ◽

Glucose Tolerance ◽

Glucose Absorption ◽

Glucose Tolerance Status

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Human Milk Microbiome of Healthy Indian Mothers is Dominated by Genus Pseudomonas

Journal of Human Lactation ◽

10.1177/08903344211048415 ◽

2021 ◽

pp. 089033442110484

Author(s):

Sourabh Dutta ◽

Bhabatosh Das ◽

Tarini Shankar Ghosh ◽

Shakti Kumar ◽

Raj Kumari Kaushal ◽

...

Keyword(s):

Human Milk ◽

Relative Abundance ◽

Tertiary Care ◽

Shannon Index ◽

Care Hospital ◽

Microbial Composition ◽

Indian Women ◽

Milk Samples ◽

Indian Mothers ◽

High Diversity

Background: The composition of the human milk microbiome is highly variable and multifactorial. Milk microbiota from various countries show striking differences. There is a paucity of data from healthy lactating Indian mothers. Research Aim: To describe the milk microbiota of healthy North Indian women, using a culture-independent, targeted metagenomic approach. Methods: We recruited exclusively breastfeeding mothers ( N = 22) who had vaginally delivered full-term singleton infants in a tertiary care hospital less than 1 week previously and had not recently consumed systemic antibiotics. Milk samples (5 ml) were collected aseptically, and microbial deoxyribonucleic acid was extracted. Microbial composition and diversity were determined using a 454-pyrosequencing platform. Core genera were identified, and their relative abundances ranked. Heatmaps showing the variation of the ranked abundances and Shannon index were obtained using R. Results: Participants (all exclusively vegetarian) had a mean ( SD) age of 27.2 (3.4) years, postnatal age of 3.9 (1.6) days and gestation 38 (1.2) weeks. The dominant phylum was Proteobacterium (relative abundance 84%) and dominant genus Pseudomonas (relative abundance 61.78%). Eleven species of Pseudomonas were identified, all generally considered nonpathogenic. Based on abundance patterns of the core genera, the milk samples could be grouped: (a) dominated by Pseudomonas with low diversity; (b) less Pseudomonas and high diversity; and (c) dominated by Pseudomonas but high diversity. All neonates were healthy and gaining weight well at 1 month of age. Conclusions: Healthy, lactating, vegetarian, North Indian women who deliver at term gestation and have no recent exposure to antibiotics, have a unique milk microbiome dominated by Pseudomonas.

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Targeted LC-ESI-MS2 characterization of human milk oligosaccharide diversity at 6 to 16 weeks post-partum reveals clear staging effects and distinctive milk groups

Analytical and Bioanalytical Chemistry ◽

10.1007/s00216-020-02819-x ◽

2020 ◽

Vol 412 (25) ◽

pp. 6887-6907 ◽

Cited By ~ 1

Author(s):

Marko Mank ◽

Hans Hauner ◽

Albert J. R. Heck ◽

Bernd Stahl

Keyword(s):

Human Milk ◽

Post Partum ◽

Principal Component ◽

Structural Diversity ◽

Preliminary Evidence ◽

Healthy Development ◽

Milk Samples ◽

Group I ◽

The Impact ◽

Automatic Grouping

Abstract Many molecular components in human milk (HM), such as human milk oligosaccharides (HMOs), assist in the healthy development of infants. It has been hypothesized that the functional benefits of HM may be highly dependent on the abundance and individual fine structures of contained HMOs and that distinctive HM groups can be defined by their HMO profiles. However, the structural diversity and abundances of individual HMOs may also vary between milk donors and at different stages of lactations. Improvements in efficiency and selectivity of quantitative HMO analysis are essential to further expand our understanding about the impact of HMO variations on healthy early life development. Hence, we applied here a targeted, highly selective, and semi-quantitative LC-ESI-MS2 approach by analyzing 2 × 30 mature human milk samples collected at 6 and 16 weeks post-partum. The analytical approach covered the most abundant HMOs up to hexasaccharides and, for the first time, also assigned blood group A and B tetrasaccharides. Principal component analysis (PCA) was employed and allowed for automatic grouping and assignment of human milk samples to four human milk groups which are related to the maternal Secretor (Se) and Lewis (Le) genotypes. We found that HMO diversity varied significantly between these four HM groups. Variations were driven by HMOs being either dependent or independent of maternal genetic Se and Le status. We found preliminary evidence for an additional HM subgroup within the Se- and Le-positive HM group I. Furthermore, the abundances of 6 distinct HMO structures (including 6′-SL and 3-FL) changed significantly with progression of lactation.

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Quality Assurance in Lactation: Reliability of OM-6050 Station System to Test Mother’s Milk Osmolality

Journal of Human Lactation ◽

10.1177/0890334420976124 ◽

2020 ◽

pp. 089033442097612

Author(s):

Laura Macias-Muñoz ◽

Ana Herranz Barbero ◽

Robin Wijngaard ◽

Mª. Dolors Salvia-Roigés ◽

Naira Rico

Keyword(s):

Human Milk ◽

Coefficient Of Variation ◽

Neonatal Intensive Care ◽

Gastrointestinal Symptoms ◽

Clinical Practices ◽

Preterm Baby ◽

Milk Samples ◽

Mother's Milk ◽

The Mean ◽

Mother’S Milk

Background Mother’s own milk does not provide enough nutrients to feed a preterm baby born before 32 weeks’ gestation; therefore, human milk fortifiers are needed. However, human milk fortifiers increase the osmolality, and enteral administration of high osmolality fluids has been associated with gastrointestinal symptoms. For this reason, it is necessary for laboratories to have a validated system in order to measure human milk osmolality. Research aim The aim of this study was to validate the OM-6050 Station System for measuring the osmolality of fortified mother’s milk samples. Methods Osmolality was measured using the osmometer OM-6050 Station System. Milk samples from healthy mothers ( N = 3) unfortified and with two fortifiers (Almirón Fortifier® or NAN FM85®), as well as a nutritional supplement (Duocal MCT®) were used in the validation study through precision and linearity analysis. Results In the precision study the mean intra-assay coefficient of variation was 1.2% and 1.7% for mother’s milk and fortified mother’s milk, respectively. The mean inter-assay coefficient of variation was ≤ 1% in both cases. In the linearity study the regression analysis had a linear response to fortified mother’s milk osmolality between 294 mOsm/kg and 539 mOsm/kg. Conclusion The osmometer OM-6050 Station was reliable for determining the osmolality of fortified and unfortified mother’s milk. It may be useful in the clinical practices within Neonatal Intensive Care Units.

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Associations between human milk oligosaccharides and growth in infancy and early childhood

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqaa010 ◽

2020 ◽

Vol 111 (4) ◽

pp. 769-778 ◽

Cited By ~ 10

Author(s):

Hanna Lagström ◽

Samuli Rautava ◽

Helena Ollila ◽

Anne Kaljonen ◽

Olli Turta ◽

...

Keyword(s):

Human Milk ◽

Causal Relation ◽

Mode Of Delivery ◽

Child Growth ◽

Birth Cohort Study ◽

Human Milk Oligosaccharides ◽

Milk Oligosaccharides ◽

Milk Samples ◽

Prepregnancy Bmi ◽

The Impact

ABSTRACT Background Breastfeeding modulates infant growth and protects against the development of obesity. However, whether or not maternal variation in human milk components, such as human milk oligosaccharides (HMOs), is associated with programming of child growth remains unknown. Objective Our objective was to determine the association between maternal HMO composition and child growth during the first 5 y of life. In addition, the association between maternal prepregnancy BMI and HMO composition was assessed. Methods Human milk samples from 802 mothers were obtained from a prospective population-based birth cohort study, Steps to healthy development of Children (STEPS), conducted in Turku, Finland. HMO composition in these milk samples was analyzed by HPLC. Child growth data from 3 mo to 5 y were collected from municipal well-baby clinics and linked to maternal HMO composition data to test for associations. Results Maternal HMO composition 3 mo after delivery was associated with height and weight during the first 5 y of life in children of secretor mothers. Specifically, HMO diversity and the concentration of lacto-N-neo-tetraose (LNnT) were inversely associated and that of 2′-fucosyllactose (2′FL) was directly associated with child height and weight z scores in a model adjusted for maternal prepregnancy BMI, mode of delivery, birthweight z score, sex, and time. Maternal prepregnancy BMI was associated with HMO composition. Conclusions The association between maternal HMO composition and childhood growth may imply a causal relation, which warrants additional testing in preclinical and clinical studies, especially since 2′FL and LNnT are among the HMOs now being added to infant formula. Furthermore, altered HMO composition may mediate the impact of maternal prepregnancy BMI on childhood obesity, which warrants further investigation to establish the cause-and-effect relation.

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