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1. Maternal and infant predictors of proinflammatory milk immune activity in Kilimanjaro , Tanzania

   https://doi.org/10.1002/ajhb.24061  

   Wander, Katherine ; Fujita, Masako ; Mattison, Siobhán ; Gauck, Megan ; Duris, Margaret ; Kiwelu, Ireen ; Mmbaga, Blandina T. ( March 2024 , American Journal of Human Biology)

   The immune system of milk (ISOM) creates a mother–infant immune axis that plays an important role in protecting infants against infectious disease (ID). Tradeoffs in the immune system suggest the potential for both protection and harm, so we conceive of two dimensions via which the ISOM impacts infants: promotion of protective activity and control of activity directed at benign targets. High variability in ISOM activity across mother–infant dyads suggests investment the ISOM may have evolved to be sensitive to maternal and/or infant characteristics. We assessed predictors of appropriate and misdirected proinflammatory ISOM activity in an environment of high ID risk, testing predictions drawn from life history theory and other evolutionary perspectives.

   We characterized milk in vitro interleukin‐6 (IL‐6) responses toSalmonella enterica(a target of protective immune activity;N = 96) andEscherichia coli(a benign target;N = 85) among mother–infant dyads in rural Kilimanjaro, Tanzania. We used ordered logistic regression and mixture models to evaluate maternal and infant characteristics as predictors of IL‐6 responses.

   In all models, IL‐6 responses toS.entericaincreased with maternal age and decreased with gravidity. In mixture models, IL‐6 responses toE.colideclined with maternal age and increased with gravidity. No other considered variables were consistently associated with IL‐6 responses.

   The ISOM's capacities for appropriate proinflammatory activity and control of misdirected proinflammatory activity increases with maternal age and decreases with gravidity. These findings are consistent with the hypothesis that the mother–infant immune axis has evolved to respond to maternal life history characteristics.

    

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2. The evolutionary ecology of breastmilk folate among Ariaal agro-pastoralists in Kenya

   Fujita, M ; Paredes Ruvalcaba, N ; Corbitt, N. ( January 2018 , American journal of physical anthropology)

   Objective: Folate in breastmilk has important implications for offspring health and survival given the essential role of this vitamin in DNA synthesis, epigenetic functions, and amino acid metabolism. Yet, little is understood about the variation of folate in breastmilk and transfer across the postpartum year and beyond. Published studies tend to be limited to milk during days/weeks postpartum, and none applied an evolutionary perspective of parental investment. Methods: A secondary analysis of the data and specimens from 200 breastfeeding mothers within 1.5 years postpartum in food-insecure northern Kenya was conducted. ELISA determined folate-binding protein (FOLR1) in cryogenically archived breastmilk and maternal blood specimens, originally collected in 2006. Maternal folate was defined as blood serum FOLR1 multiplied by –1 because elevated FOLR1 is associated with folate deficiency. The concentration of milk FOLR1 was evaluated in relation to maternal folate and 1) infant sex (Trivers-Willard hypothesis), 2) time postpartum and parity (maternal residual reproductive value) using regression models adjusted for covariates. Results indicated: 1) no Trivers-Willard effect; 2) support for time postpartum but not for parity. Maternal folate and time postpartum inversely predicted milk FOLR1. There was an interaction between these variables (p<0.05). Maternal folate improved over time at a varying rate while milk FOLR1 decreased at a relatively steady rate. This inverse relationship became stronger as time advanced. Conclusion: The priority shift from the investment in current offspring toward maternal soma and potential future offspring in this study provides empirical support for the evolutionary hypothesis of parental investment and parent-offspring conflict. This study was funded by NSF (BCS #1638167), and the Wenner-Gren Foundation (Grant #9278). The original data/specimen collection was supported by NSF (BCS #0622358) and the Wenner-Gren Foundation (Grant #7460). 

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3. Characterizing the extent human milk folate is buffered against maternal malnutrition and infection in drought‐stricken northern Kenya

   https://doi.org/10.1002/ajpa.24603  

   Fujita, Masako ; Wander, Katherine ; Tran, Tin ; Brindle, Eleanor ( August 2022 , American Journal of Biological Anthropology)

   Folate is an essential nutrient fundamental to human growth and development. Human milk maintains high folate content across the maternal folate status range, suggesting buffering of milk folate with prioritized delivery to milk at the expense of maternal depletion. We investigated whether and how the extent of this buffering may diminish under prolonged nutritional and/or disease stress, while taking into consideration infants' varying vulnerability to malnutrition‐related morbidity/mortality.

   A cross‐sectional study analyzed milk specimens from northern Kenyan mothers (n = 203), surveyed during a historic drought and ensuing food shortage. Multiple regression models for folate receptor‐α (FOLR1) in milk were constructed. Predictors included maternal underweight (BMI < 18.5), iron‐deficiency anemia (hemoglobin <12 g/dl and dried‐blood‐spot transferrin receptor >5 mg/L), folate deficiency (hyperhomocysteinemia, homocysteine >12 or 14 μmol/L), inflammation (serum C‐reactive protein >5 mg/L), infant age and sex, and mother‐infant interactions.

   In adjusted models, milk FOLR1 was unassociated with maternal underweight, iron‐deficiency anemia and inflammation. FOLR1 was positively associated with maternal folate deficiency, and inversely associated with infant age. There was interaction between infant age and maternal underweight, and between infant sex and maternal folate deficiency, predicting complex changes in FOLR1.

   Our results suggest that mothers buffer milk folate against their own nutritional stress even during a prolonged drought; however, the extent of this buffering may vary with infant age, and, among folate‐deficient mothers, with infant sex. Future research is needed to better understand this variability in maternal buffering of milk folate and how it relates to folate status in nursing infants.

    

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4. Gut microbiome composition of wild western lowland gorillas is associated with individual age and sex factors

   https://doi.org/10.1002/ajpa.23842  

   Pafčo, Barbora ; Sharma, Ashok K. ; Petrželková, Klára J. ; Vlčková, Klára ; Todd, Angelique ; Yeoman, Carl J. ; Wilson, Brenda A. ; Stumpf, Rebecca ; White, Bryan A. ; Nelson, Karen E. ; et al ( April 2019 , American Journal of Physical Anthropology)

   Environmental and ecological factors, such as geographic range, anthropogenic pressure, group identity, and feeding behavior are known to influence the gastrointestinal microbiomes of great apes. However, the influence of individual host traits such as age and sex, given specific dietary and social constraints, has been less studied. The objective of this investigation was to determine the associations between an individual's age and sex on the diversity and composition of the gut microbiome in wild western lowland gorillas.

   Publicly available 16S rRNA data generated from fecal samples of different groups ofGorilla gorillagorillain the Central African Republic were downloaded and bioinformatically processed. The groups analyzed included habituated, partially habituated and unhabituated gorillas, sampled during low fruit (dry,n = 28) and high fruit (wet,n = 82) seasons. Microbial community analyses (alpha and beta diversity and analyses of discriminant taxa), in tandem with network‐wide approaches, were used to (a) mine for specific age and sex based differences in gut bacterial community composition and to (b) asses for gut community modularity and bacterial taxa with potential functional roles, in the context of seasonal food variation, and social group affiliation.

   Both age and sex significantly influenced gut microbiome diversity and composition in wild western lowland gorillas. However, the largest differences were observed between infants and adults in habituated groups and between adults and immature gorillas within all groups, and across dry and wet seasons. Specifically, although adults always showed greater bacterial richness than infants and immature gorillas, network‐wide analyses showed higher microbial community complexity and modularity in the infant gorilla gut. Sex‐based microbiome differences were not evident among adults, being only detected among immature gorillas.

   The results presented point to a dynamic gut microbiome inGorillaspp., associated with ontogeny and individual development. Of note, the gut microbiomes of breastfeeding infants seemed to reflect early exposure to complex, herbaceous vegetation. Whether increased compositional complexity of the infant gorilla gut microbiome is an adaptive response to an energy‐limited diet and an underdeveloped gut needs to be further tested. Overall, age and sex based gut microbiome differences, as shown here, maybe mainly attributed to access to specific feeding sources, and social interactions between individuals within groups.

    

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

   https://doi.org/10.1002/ajp.22544  

   Bernstein, Robin M. ; Hinde, Katie ( March 2016 , American Journal of Primatology)

   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‐β₂). 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‐β₂. Mothers of daughters produced milk with higher TGF‐β₂. 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‐β₂) 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.

    

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