Human milk: From complex tailored nutrition to bioactive impact on child cognition and behavior.

Human milk is a highly complex liquid food tailor-made to match an infant's needs. Beyond documented positive effects of breastfeeding on infant and maternal health, there is increasing evidence that milk constituents also impact child neurodevelopment. Non-nutrient milk bioactives would contribute to the (long-term) development of child cognition and behavior, a process termed 'Lactocrine Programming'. In this review we discuss the current state of the field on human milk composition and its links with child cognitive and behavioral development. To promote state-of-the-art methodologies and designs that facilitate data pooling and meta-analytic endeavors, we present detailed recommendations and best practices for future studies. Finally, we determine important scientific gaps that need to be filled to advance the field, and discuss innovative directions for future research. Unveiling the mechanisms underlying the links between human milk and child cognition and behavior will deepen our understanding of the broad functions of this complex liquid food, as well as provide necessary information for designing future interventions.

Human Milk Oligosaccharide Compositions Illustrate Global Variations in Early Nutrition.

BACKGROUND: Human milk oligosaccharides (HMOs) are an abundant class of compounds found in human milk and have been linked to the development of the infant, and specifically the brain, immune system, and gut microbiome. OBJECTIVES: Advanced analytical methods were used to obtain relative quantitation of many structures in approximately 2000 samples from over 1000 mothers in urban, semirural, and rural sites across geographically diverse countries. METHODS: LC-MS-based analytical methods were used to profile the compounds with broad structural coverage and quantitative information. The profiles revealed their structural heterogeneity and their potential biological roles. Comparisons of HMO compositions were made between mothers of different age groups, lactation periods, infant sexes, and residing geographical locations. RESULTS: A common behavior found among all sites was a decrease in HMO abundances during lactation until approximately postnatal month 6, where they remained relatively constant. The greatest variations in structural abundances were associated with the presence of α(1,2)-fucosylated species. Genomic analyses of the mothers were not performed; instead, milk was phenotyped according to the abundances of α(1,2)-fucosylated structures. Mothers from the South American sites tended to have higher proportions of phenotypic secretors [mothers with relatively high concentrations of α(1,2)-fucosylated structures] in their populations compared to the rest of the globe, with Bolivia at ∼100% secretors, Peru at ∼97%, Brazil at ∼90%, and Argentina at ∼85%. Conversely, the cohort sampled in Africa manifested the lowest proportion of secretors (South Africa ∼ 63%, the Gambia ∼ 64%, and Malawi ∼ 75%). Furthermore, we compared total abundances of HMOs in secretors compared with nonsecretors and found that nonsecretors have lower abundances of HMOs compared to secretors, regardless of geographical location. We also observed compositional differences of the 50+ most abundant HMOs between milk types and geographical locations. CONCLUSIONS: This study represents the largest structural HMO study to date and reveals the general behavior of HMOs during lactation among different populations.

Integrative approaches to dispersing science: A case study of March Mammal Madness.

OBJECTIVES: Public engagement is increasingly viewed as an important pillar of scientific scholarship. For early career and established scholars, navigating the mosaic landscape of public education and science communication, noted for rapid "ecological" succession, can be daunting. Moreover, academics are characterized by diverse skills, motivations, values, positionalities, and temperaments that may differentially incline individuals to particular public translation activities. METHODS: Here we briefly contextualize engagement activities within a scholarly portfolio, describe the use of one public education program-March Mammal Madness (MMM)- to highlight approaches to science communication, and explore essential elements and practical considerations for creating and sustaining outreach pursuits in tandem with other scholarly activities. RESULTS: MMM, an annual simulated tournament of living and fossil animal taxa, has reached hundreds of thousands of learners since 2013. This program has provided a platform to communicate research findings from biology and anthropology and showcase numerous scholars in these fields. MMM has leveraged tournament devices to intentionally address topics of climate change, capitalist environmental degradation, academic sexism, and racist settler-colonialism. The tournament, however, has also perpetuated implicit biases that need disrupting. CONCLUSIONS: By embracing reflexive, self-interrogative, and growth attitudes, the tournament organizers iteratively refine and improve this public science education program to better align our activities with our values and goals. Our experiences with MMM suggest that dispersing science is most sustainable when we combine ancestral adaptations for cooperation, community, and storytelling with good-natured competition in the context of shared experiences and shared values.

Breastfeeding and the origins of health: Interdisciplinary perspectives and priorities.

Breastfeeding and human milk (HM) are critically important to maternal, infant and population health. This paper summarizes the proceedings of a workshop that convened a multidisciplinary panel of researchers to identify key priorities and anticipated breakthroughs in breastfeeding and HM research, discuss perceived barriers and challenges to achieving these breakthroughs and propose a constructive action plan to maximize the impact of future research in this field. Priority research areas identified were as follows: (1) addressing low breastfeeding rates and inequities using mixed methods, community partnerships and implementation science approaches; (2) improving awareness of evidence-based benefits, challenges and complexities of breastfeeding and HM among health practitioners and the public; (3) identifying differential impacts of alternative modes of HM feeding including expressed/pumped milk, donor milk and shared milk; and (4) developing a mechanistic understanding of the health effects of breastfeeding and the contributors to HM composition and variability. Key barriers and challenges included (1) overcoming methodological limitations of epidemiological breastfeeding research and mechanistic HM research; (2) counteracting 'breastfeeding denialism' arising from negative personal breastfeeding experiences; (3) distinguishing and aligning research and advocacy efforts; and (4) managing real and perceived conflicts of interest. To advance research on breastfeeding and HM and maximize the reach and impact of this research, larger investments are needed, interdisciplinary collaboration is essential, and the scientific community must engage families and other stakeholders in research planning and knowledge translation.

Barium distributions in teeth reveal early-life dietary transitions in primates.

Early-life dietary transitions reflect fundamental aspects of primate evolution and are important determinants of health in contemporary human populations. Weaning is critical to developmental and reproductive rates; early weaning can have detrimental health effects but enables shorter inter-birth intervals, which influences population growth. Uncovering early-life dietary history in fossils is hampered by the absence of prospectively validated biomarkers that are not modified during fossilization. Here we show that large dietary shifts in early life manifest as compositional variations in dental tissues. Teeth from human children and captive macaques, with prospectively recorded diet histories, demonstrate that barium (Ba) distributions accurately reflect dietary transitions from the introduction of mother's milk through the weaning process. We also document dietary transitions in a Middle Palaeolithic juvenile Neanderthal, which shows a pattern of exclusive breastfeeding for seven months, followed by seven months of supplementation. After this point, Ba levels in enamel returned to baseline prenatal levels, indicating an abrupt cessation of breastfeeding at 1.2 years of age. Integration of Ba spatial distributions and histological mapping of tooth formation enables novel studies of the evolution of human life history, dietary ontogeny in wild primates, and human health investigations through accurate reconstructions of breastfeeding history.

Steroid hormone concentrations in milk predict sex-specific offspring growth in a nonhuman primate.

OBJECTIVES: In humans and other mammals, maternal hormones are transferred to offspring during lactation via milk and may regulate postnatal development, including the pace of early growth. Here, we used a nonhuman primate model to test the hypotheses that milk cortisol and dehydroepiandrosterone-sulfate (DHEAS) concentrations reflect maternal characteristics, and that changes in these hormones across lactation are associated with early postnatal growth rates. METHODS: Demographic information, morphometrics, and milk samples were collected from rhesus macaque mothers and their infants at the California National Primate Research Center in Davis, California. Using linear models, we examined the relationship between maternal traits and milk hormone concentrations (N = 104 females) and explored the effect of milk hormones on the rate of offspring growth (N = 72 mother-infant dyads), controlling for available milk energy. RESULTS: Contrary to previous studies, we found that milk cortisol concentrations were categorically higher in multiparous females than in primiparous females. However, milk DHEAS concentrations decreased with maternal parity. Neither milk cortisol nor DHEAS were related to maternal rank. Finally, changes in milk hormones predicted offspring growth in a sex-specific and temporal manner: increases in cortisol from peak to late lactation predicted faster female growth, and increases in DHEAS concentrations from early to peak and peak to late lactation predicted faster male growth. CONCLUSIONS: Our findings shed light on how hormonal components of milk have sex-specific effects on offspring growth during early postnatal life with varying temporal windows of sensitivity.

Diversity and temporal dynamics of primate milk microbiomes.

Milk is inhabited by a community of bacteria and is one of the first postnatal sources of microbial exposure for mammalian young. Bacteria in breast milk may enhance immune development, improve intestinal health, and stimulate the gut-brain axis for infants. Variation in milk microbiome structure (e.g., operational taxonomic unit [OTU] diversity, community composition) may lead to different infant developmental outcomes. Milk microbiome structure may depend on evolutionary processes acting at the host species level and ecological processes occurring over lactation time, among others. We quantified milk microbiomes using 16S rRNA high-throughput sequencing for nine primate species and for six primate mothers sampled over lactation. Our data set included humans (Homo sapiens, Philippines and USA) and eight nonhuman primate species living in captivity (bonobo [Pan paniscus], chimpanzee [Pan troglodytes], western lowland gorilla [Gorilla gorilla gorilla], Bornean orangutan [Pongo pygmaeus], Sumatran orangutan [Pongo abelii], rhesus macaque [Macaca mulatta], owl monkey [Aotus nancymaae]) and in the wild (mantled howler monkey [Alouatta palliata]). For a subset of the data, we paired microbiome data with nutrient and hormone assay results to quantify the effect of milk chemistry on milk microbiomes. We detected a core primate milk microbiome of seven bacterial OTUs indicating a robust relationship between these bacteria and primate species. Milk microbiomes differed among primate species with rhesus macaques, humans and mantled howler monkeys having notably distinct milk microbiomes. Gross energy in milk from protein and fat explained some of the variations in microbiome composition among species. Microbiome composition changed in a predictable manner for three primate mothers over lactation time, suggesting that different bacterial communities may be selected for as the infant ages. Our results contribute to understanding ecological and evolutionary relationships between bacteria and primate hosts, which can have applied benefits for humans and endangered primates in our care.

Cortisol in Neonatal Mother's Milk Predicts Later Infant Social and Cognitive Functioning in Rhesus Monkeys.

Milk provides not only the building blocks for somatic development but also the hormonal signals that contribute to the biopsychological organization of the infant. Among mammals, glucocorticoids (GCs) in mother's milk have been associated with infant temperament. This study extended prior work to investigate rhesus monkey (Macaca mulatta) mother-infant dyads (N = 34) from birth through 8 months postpartum. Regression analysis revealed that cortisol concentrations in milk during the neonatal period predicted impulsivity on a cognitive task, but not global social behaviors, months later. During this time period, sex-differentiated social behavior emerged. For female infants, milk cortisol concentrations predicted total frequency of play. Collectively, these findings support and extend the "lactational programming" hypothesis on the impact of maternal-origin hormones ingested via milk.

Age at reproductive debut: Developmental predictors and consequences for lactation, infant mass, and subsequent reproduction in rhesus macaques (Macaca mulatta).

OBJECTIVES: The age at which females initiate their reproductive career is a critical life-history parameter with potential consequences on their residual reproductive value and lifetime fitness. The age at reproductive debut may be intimately tied to the somatic capacity of the mother to rear her young, but relatively little is known about the influence of age of first birth on milk synthesis within a broader framework of reproductive scheduling, infant outcomes, and other life-history tradeoffs. MATERIAL AND METHODS: Our study investigated the predictors of age at first reproduction among 108 captive rhesus macaque (Macaca mulatta) females, and associations with their milk synthesis at peak lactation, infant mass, and ability to subsequently conceive and reproduce. RESULTS: The majority of females reproduced in their fourth year (typical breeders); far fewer initiated their reproductive career one year earlier or one year later (respectively early and late breeders). Early breeders (3-year-old) benefited from highly favorable early life development (better juvenile growth, high dominance rank) to accelerate reproduction, but were impaired in milk synthesis due to lower somatic resources and their own continued growth. Comparatively, late breeders suffered from poor developmental conditions, only partially compensated by their delayed reproduction, and evinced compromised milk synthesis. Typical breeders not only produced higher available milk energy but also had best reproductive performance during the breeding and birth seasons following primiparity. DISCUSSION: Here, we refine and extend our understanding of how life-history tradeoffs manifest in the magnitude, sources, and consequences of variation in age of reproductive debut. These findings provide insight into primate reproductive flexibility in the context of constraints and opportunities.

Breast Milk of HIV-Positive Mothers Has Potent and Species-Specific In Vivo HIV-Inhibitory Activity.

UNLABELLED: Despite the nutritional and health benefits of breast milk, breast milk can serve as a vector for mother-to-child HIV transmission. Most HIV-infected infants acquire HIV through breastfeeding. Paradoxically, most infants breastfed by HIV-positive women do not become infected. This is potentially attributed to anti-HIV factors in breast milk. Breast milk of HIV-negative women can inhibit HIV infection. However, the HIV-inhibitory activity of breast milk from HIV-positive mothers has not been evaluated. In addition, while significant differences in breast milk composition between transmitting and nontransmitting HIV-positive mothers have been correlated with transmission risk, the HIV-inhibitory activity of their breast milk has not been compared. This knowledge may significantly impact the design of prevention approaches in resource-limited settings that do not deny infants of HIV-positive women the health benefits of breast milk. Here, we utilized bone marrow/liver/thymus humanized mice to evaluate the in vivo HIV-inhibitory activity of breast milk obtained from HIV-positive transmitting and nontransmitting mothers. We also assessed the species specificity and biochemical characteristics of milk's in vivo HIV-inhibitory activity and its ability to inhibit other modes of HIV infection. Our results demonstrate that breast milk of HIV-positive mothers has potent HIV-inhibitory activity and indicate that breast milk can prevent multiple routes of infection. Most importantly, this activity is unique to human milk. Our results also suggest multiple factors in breast milk may contribute to its HIV-inhibitory activity. Collectively, our results support current recommendations that HIV-positive mothers in resource-limited settings exclusively breastfeed in combination with antiretroviral therapy. IMPORTANCE: Approximately 240,000 children become infected with HIV annually, the majority via breastfeeding. Despite daily exposure to virus in breast milk, most infants breastfed by HIV-positive women do not acquire HIV. The low risk of breastfeeding-associated HIV transmission is likely due to antiviral factors in breast milk. It is well documented that breast milk of HIV-negative women can inhibit HIV infection. Here, we demonstrate, for the first time, that breast milk of HIV-positive mothers (nontransmitters and transmitters) inhibits HIV transmission. We also demonstrate that breast milk can prevent multiple routes of HIV acquisition and that this activity is unique to human milk. Collectively, our results support current guidelines which recommend that HIV-positive women in resource-limited settings exclusively breastfeed in combination with infant or maternal antiretroviral therapy.

Bioactive factors in milk across lactation: Maternal effects and influence on infant growth in rhesus macaques (Macaca mulatta).

Among mammals, numerous bioactive factors in milk vary across mothers and influence offspring outcomes. This emerging area of research has primarily investigated such dynamics within rodent biomedical models, domesticated dairy breeds, and among humans in clinical contexts. Less understood are signaling factors in the milk of non-human primates. Here, we report on multiple bioactive components in rhesus macaque (Macaca mulatta) milk and their associations with maternal and infant characteristics. Milk samples were collected from 59 macaques at multiple time points across lactation in conjunction with maternal and infant morphometrics and life-history animal records. Milk was assayed for adiponectin (APN), epidermal growth factor (EGF) and its receptor (EGF-R), and transforming growth factor beta 2 (TGF-ß2 ). Regression models were constructed to assess the contributions of maternal factors on variation in milk bioactives, and on the relationship of this variation to infant body mass and growth. Maternal body mass, parity, social rank, and infant sex were all predictive of concentrations of milk bioactives. Primiparous mothers produced milk with higher adiponectin, but lower EGF, than multiparous mothers. Heavier mothers produced milk with lower EGF and EGF-R, but higher TGF-ß2 . Mothers of daughters produced milk with higher TGF-ß2 . Mid-ranking mothers produced milk with higher mean EGF and adiponectin concentrations than low-ranking mothers. Milk EGF and EGF-R were positively associated with infant body mass and growth rate. Importantly, these signaling bioactives (APN, EGF, EGF-R, and TGF-ß2 ) were significantly correlated with nutritional values of milk. The effects of milk signals remained after controlling for the available energy in milk revealing the added physiological role of non-nutritive milk bioactives in the developing infant. Integrating analyses of energetic and other bioactive components of milk yields an important perspective for interpreting the magnitude, sources, and consequences of inter-individual variation in milk synthesis. Am. J. Primatol. 78:838-850, 2016. © 2016 Wiley Periodicals, Inc.

Comparative Proteomics of Human and Macaque Milk Reveals Species-Specific Nutrition during Postnatal Development.

Milk has been well established as the optimal nutrition source for infants, yet there is still much to be understood about its molecular composition. Therefore, our objective was to develop and compare comprehensive milk proteomes for human and rhesus macaques to highlight differences in neonatal nutrition. We developed a milk proteomics technique that overcomes previous technical barriers including pervasive post-translational modifications and limited sample volume. We identified 1606 and 518 proteins in human and macaque milk, respectively. During analysis of detected protein orthologs, we identified 88 differentially abundant proteins. Of these, 93% exhibited increased abundance in human milk relative to macaque and include lactoferrin, polymeric immunoglobulin receptor, alpha-1 antichymotrypsin, vitamin D-binding protein, and haptocorrin. Furthermore, proteins more abundant in human milk compared with macaque are associated with development of the gastrointestinal tract, the immune system, and the brain. Overall, our novel proteomics method reveals the first comprehensive macaque milk proteome and 524 newly identified human milk proteins. The differentially abundant proteins observed are consistent with the perspective that human infants, compared with nonhuman primates, are born at a slightly earlier stage of somatic development and require additional support through higher quantities of specific proteins to nurture human infant maturation.

Breastfeeding over two years is associated with longer birth intervals, but not measures of growth or health, among children in Kilimanjaro, TZ.

OBJECTIVES: Breastfeeding has been associated with numerous health and well-being benefits for both children and their mothers, including prolonging the birth interval to the subsequent sibling. The clearest associations between breastfeeding and health outcomes, per se, reflect exclusive breastfeeding in the first months of postnatal life and are most evident during infancy. Fewer studies explore the consequences of breastfeeding for multiple years. In this article, we ask whether breastfeeding for more than 2 years is associated with discernible health and well-being benefits to children. METHODS: Data were collected from 315 children, aged 2 to 7, and their caretakers residing in Kilimanjaro, Tanzania. Basic demographic and health information was solicited, and anthropometric and blood markers of health were evaluated. RESULTS: Our results indicate a strong positive relationship between breastfeeding for 2 or more years and interbirth interval, but little evidence for a relationship between prolonged breastfeeding and several indicators of child growth and health. CONCLUSIONS: We suggest that these relationships may support the recently rekindled birth spacing hypothesis, positing selection for longer interbirth intervals, rather than, or in addition to, more direct health benefits associated with breastfeeding for 2 or more years. Our results may indicate attenuating health benefits associated with longer breastfeeding.

Offspring of primiparous mothers do not experience greater mortality or poorer growth: Revisiting the conventional wisdom with archival records of Rhesus Macaques.

Female mammals often begin to reproduce before achieving somatic maturity and therefore face tradeoffs between allocating energy to reproduction or their own continued development. Constraints on primiparous females are associated with greater reproductive failure, and first-born infants often have slower growth and greater mortality and morbidity than infants born to multiparous females. Effects of early life investment may persist even after weaning when juveniles are no longer dependent on maternal care and mother's milk. We investigated the long-term consequences of birth order in a large sample of rhesus macaques, Macaca mulatta, assigned to the outdoor breeding colony at the California National Primate Research Center (n = 2,724). A joint model for growth and mortality over the first three years of life allowed us to explicitly connect growth rates to survival. As expected, males are born heavier and grow faster relative to females. However, contrary to expectations, later-born males face substantially lower survival probability during their first three years, whereas first-born males survive at greater rates similar to both first-born and later-born females. Primiparous mothers are less likely to conceive during the subsequent breeding season, suggesting that their reproductive costs are greater than those of multiparous mothers. We speculate that compensatory tactics, both behavioral and physiological, of first-born offspring and their mothers, as well as the novel ecology of the captive environment, underlie these findings. The results presented here provide new insights into how maternal and infant life history tradeoffs may influence developmental trajectories even after the period of maternal dependence. Am. J. Primatol. 77:963-973, 2015. © 2015 Wiley Periodicals, Inc.

Intra- and interspecific variation in macaque molar enamel thickness.

Enamel thickness has played an important role in studies of primate taxonomy, phylogeny, and functional morphology, although its variation among hominins is poorly understood. Macaques parallel hominins in their widespread geographic distribution, relative range of body sizes, and radiation during the last five million years. To explore enamel thickness variation, we quantified average and relative enamel thickness (AET and RET) in Macaca arctoides, Macaca fascicularis, Macaca fuscata, Macaca mulatta, Macaca nemestrina, and Macaca sylvanus. Enamel area, dentine area, and enamel-dentine junction length were measured from mesial sections of 386 molars scanned with micro-computed tomography, yielding AET and RET indices. Intraspecific sex differences were not found in AET or RET. Macaca fuscata had the highest AET and RET, M. fascicularis showed the lowest AET, and M. arctoides had the lowest RET. The latitudinal distribution of macaque species was associated with AET for these six species. Temperate macaques had thicker molar enamel than did tropical macaques, suggesting that thick enamel may be adaptive in seasonal environments. Additional research is needed to determine if thick enamel in temperate macaques is a response to intensified hard-object feeding, increased abrasion, and/or a broader diet with a greater range of food material properties. The extreme ecological flexibility of macaques may prohibit identification of consistent trends between specific diets and enamel thickness conditions. Such complications of interpretation of ecological variability, dietary diversity, and enamel thickness may similarly apply for fossil Homo species.

Balancing Act: an Interdisciplinary Exploration of Trade-offs in Reproducing Females.

Trade-offs resulting from the high demand of offspring production are a central focus of many subdisciplines within the field of biology. Yet, despite the historical and current interest on this topic, large gaps in our understanding of whole-organism trade-offs that occur in reproducing individuals remain, particularly as it relates to the nuances associated with female reproduction. This volume of Integrative and Comparative Biology (ICB) contains a series of papers that focus on reviewing trade-offs from the female-centered perspective of biology (i.e., a perspective that places female reproductive biology at the center of the topic being investigated or discussed). These papers represent some of the work showcased during our symposium held at the 2024 meeting of the Society for Integrative and Comparative Biology (SICB) in Seattle, Washington. In this roundtable discussion, we use a question-and-answer format to capture the diverse perspectives and voices involved in our symposium. We hope that the dialogue featured in this discussion will be used to motivate researchers interested in understanding trade-offs in reproducing females and provide guidance on future research endeavors.

Sequencing the transcriptome of milk production: milk trumps mammary tissue.

BACKGROUND: Studies of normal human mammary gland development and function have mostly relied on cell culture, limited surgical specimens, and rodent models. Although RNA extracted from human milk has been used to assay the mammary transcriptome non-invasively, this assay has not been adequately validated in primates. Thus, the objectives of the current study were to assess the suitability of lactating rhesus macaques as a model for lactating humans and to determine whether RNA extracted from milk fractions is representative of RNA extracted from mammary tissue for the purpose of studying the transcriptome of milk-producing cells. RESULTS: We confirmed that macaque milk contains cytoplasmic crescents and that ample high-quality RNA can be obtained for sequencing. Using RNA sequencing, RNA extracted from macaque milk fat and milk cell fractions more accurately represented RNA from mammary epithelial cells (cells that produce milk) than did RNA from whole mammary tissue. Mammary epithelium-specific transcripts were more abundant in macaque milk fat, whereas adipose or stroma-specific transcripts were more abundant in mammary tissue. Functional analyses confirmed the validity of milk as a source of RNA from milk-producing mammary epithelial cells. CONCLUSIONS: RNA extracted from the milk fat during lactation accurately portrayed the RNA profile of milk-producing mammary epithelial cells in a non-human primate. However, this sample type clearly requires protocols that minimize RNA degradation. Overall, we validated the use of RNA extracted from human and macaque milk and provided evidence to support the use of lactating macaques as a model for human lactation.

Metabolomic phenotyping validates the infant rhesus monkey as a model of human infant metabolism.

OBJECTIVES: Rhesus macaque monkeys are widely used as models for human physiology and behavior. They are particularly suited for studies on infant nutrition and metabolism; however, few studies have directly compared their metabolic or microbiological phenotypes. The aim of the present study was to compare the metabolomic profiles and microbiome of milk from human and rhesus mothers, and the metabolomic profiles of urine and serum from human and rhesus infants to establish the value of this model for human nutrition research. METHODS: Milk samples were collected from rhesus and human mothers at similar stages of lactation. Urine and serum samples were collected from breast-fed rhesus and human infants. H nuclear magnetic resonance spectra were acquired for all samples and metabolites were identified and quantified using targeted profiling techniques. The microbial community structure of milk was examined using 16S rRNA gene sequencing. RESULTS: An identical set of metabolites was identified in the urine and serum profiles from human and rhesus infants. In urine, 65% of the metabolites were present at similar concentrations, whereas ~40% were similar in serum. The gross composition of human and rhesus milk was comparable, including the overall microbial community at both the phylum and order level; however, some oligosaccharides found in human milk were not present in monkey milk. CONCLUSIONS: Comparison of the milk microbiome and urine, serum, and milk metabolome of rhesus macaques and humans has revealed substantial similarities that provide unique biological information highlighting the significance of rhesus macaques as a model for infant nutrition and developmental research.

Daughter dearest: Sex-biased calcium in mother's milk among rhesus macaques.

Mother's milk provides building blocks necessary for infant development and growth postnatally. Minerals in milk are particularly important for infant skeletal development and may reflect maternal characteristics that are associated with the capacity to synthesize milk and sex-specific developmental priorities of the infant. Using a large sample of mother-infant dyads assigned to the outdoor breeding colony at the California National Primate Research Center (N=104), we investigated the relationship of milk calcium (Ca) and phosphorus (P) concentrations and the ratio of Ca/P to maternal and infant characteristics and to other milk variables. Ca and P are largely associated with casein micelles, and as expected, both Ca and P were positively correlated with protein concentrations in milk. Neither Ca nor P concentrations were associated with maternal parity. Mothers rearing daughters tended to produce higher mean Ca concentration in milk, and consequently a higher Ca/P ratio, than did mothers rearing sons, even though protein concentration was not elevated. These results suggest that the Ca/P ratio in rhesus milk may have been under separate selective pressure from protein content to facilitate the accelerated rate of skeletal calcification that has been observed in female Macaca mulatta infants.

Field and laboratory methods in human milk research.

Human milk is a complex and variable fluid of increasing interest to human biologists who study nutrition and health. The collection and analysis of human milk poses many practical and ethical challenges to field workers, who must balance both appropriate methodology with the needs of participating mothers and infants and logistical challenges to collection and analysis. In this review, we address various collection methods, volume measurements, and ethical considerations and make recommendations for field researchers. We also review frequently used methods for the analysis of fat, protein, sugars/lactose, and specific biomarkers in human milk. Finally, we address new technologies in human milk research, the MIRIS Human Milk Analyzer and dried milk spots, which will improve the ability of human biologists and anthropologists to study human milk in field settings.