Research Project: Early Life Factors and Microbiota Impact on Healthy Development

Location: Microbiome and Metabolism Research

2025 Annual Report

Objectives
1. Evaluate the role of diet and/or physical activity on gut microbiota and its impact on health during different stages of infant and child development. 1.A Investigate the role of physical activity during gestation on microbiome composition, placental function, and immune response during pregnancy and its association to infants’ health in mothers with obesity. 1.B Evaluate how dietary patterns and micronutrient intake during transitionary phases of development (pre-adolescence through adolescence) associate with the gut, immune and brain health of children. 1.C Determine the independent and combined effects of exercise training and fruit and vegetables intake on gut and immune health of children. 1.D.Investigate the role of polyphenol-rich diet (PRD) consumption and physical activity (PA) during pregnancy on maternal gut microbiota and fetal brain development and its association with offspring cognition and sociability. 1.E. Evaluate the role of maternal microbiota on fetal brain development and offspring behavioral outcome. 2. Investigate the impact of maternal dietary components and early life stress on the gut microbiota and its impact on maternal-child health. 2.A Determine the causal contributions of microbiota during pregnancy on maternal-child health. 2.B Investigate the role of maternal dietary intervention during pregnancy on fetal growth and child health outcomes.. 2.C Determine the impact of stress on milk and gut microbiota and its association to behavioral outcomes. 3. Elucidate the role of gut microbiota and human milk components on offspring health. 3.A Elucidate the role of gut microbiota and milk bioactives on gut, immune system and brain function. 3.B Examine the role of dietary bioactives in microbiota function.

Approach
Early life factors (i.e., maternal diet, physical activity, stress, and neonatal diet) play a role in gut microbiota function and lifelong health outcomes. However, the precise mechanisms driving the health outcomes are unknown. The project plan will investigate the impact of the various early life factors on health leveraging clinical studies and animal and in vitro cell culture models. Objective 1 will investigate the impact of maternal physical activity on mitigating obesity-associated effects on the maternal immune system, microbiota, metabolism, placenta, and infant health. In addition, the impact of deficiency in micronutrients and fruit and vegetable intake by children on their gut microbiota, immune system, and brain will be investigated. Objective 2 will investigate maternal diet quality and impact of early life stress on the placenta, fetus, and offspring health. Objective 3 will examine the role of postnatal diet on gut microbiota, immune system, and brain function. The long-term goal is to develop prevention strategies for optimal child health and development. Results obtained from this project plan will inform dietary and physical activity guidelines for pregnancy, early life, and childhood to adolescence.

Progress Report
Progress was made under all 3 objectives. Under Objective 1 - scientists in ARS Little Rock, Arkansas are investigating the impact of physical activity on mitigating obesity-associated effects on the maternal immune system, microbiota, metabolism, placenta, and infant health. The impact of deficiency in micronutrients and fruit and vegetable intake by children on their gut microbiota, immune system, and brain are also being assessed. Physical activity study samples have been collected, and immune response, microbiota, metabolomics and placenta transcriptome data are being captured. For micronutrient and fruit and vegetable studies, IRB protocols have been submitted. The animal studies to evaluate the benefits of blueberry diet and physical activity prior to and during pregnancy in obesity models on fetal brain and placental tissues have been completed. Objective 2 investigated the impact of maternal microbiota, and prebiotic diet intervention on in utero effects in obese rodent models. Animal studies on the impact of early life stress during lactation on offspring health have been completed. Objective 3 studying milk bioactives and infant gut microbiota benefits to immune system and brain function are ongoing. Under 6026-10700-001-021S: Sub-objective 1A - assesses the impact of health and weight status during gestation on cardiometabolic health and brain development in offspring throughout childhood. Children born to participants in the ACNC Glowing study are participating in the follow-up study. Data collection has been completed for 55 participants at age 11 years. The first 14-year visit is scheduled for Summer 2025. 5 manuscripts have been published on the Glowing Study. Sub-objective 1B - assesses the impact of exercise during gestation on cardiometabolic health and brain development in offspring throughout childhood. Children born to participants in the ACNC Expecting study are recalled at ages 5, 8, and 11 years. Between 08/01/24 and 04/08/25, 16 children were studied. A manuscript on the effect of exercise intervention on maternal and birth outcomes has been submitted, and four other manuscripts are currently under development or nearing submission. Under Sub-objective 1C - assesses the effectiveness of a community-adapted exercise intervention during pregnancy. We completed the full pilot phase enrollment with 21 participants. Using an intention-to-treat approach, exercise session compliance was 56.9% during pregnancy. When using a per-protocol approach, compliance improved to 72.2%. We have obtained IRB approval to complete our community-embedded trial and begun recruitment and enrollment. We are preparing to submit our study protocol manuscript in July 2025. Under Sub-objective 2A - assesses the effects of paternal and child diet on nutritional adequacy, growth and immune function. The IRB protocol as well as the study specific manual of operation (MOP) have been developed and submitted. Under Sub-objective 2B - assesses the impact of allergen elimination diets on the nutritional status of multi-food allergic children. Study procedures were developed during a intramural-funded pilot study and the initial USDA study start-up period is July 2024. Study recruitment and enrollment began in late January 2025. Currently, 29 of 180 planned study participants are enrolled. In regards to Sub-objective 2A assesses the impact of a healthy meal pattern during the postpartum period on infant feeding outcomes. The study has been combined with Sub-objective 3B to design a larger RCT with prenatal and postnatal interventions. The IRB protocol is pending approval. The meal plan has been designed, the contract with the meal delivery company and an account with the grocery delivery service have been established. Under Sub-objective 3B assesses the effect of early lactation on breastfeeding outcomes in participants with elevated body weight. The study combined with Sub-objective 3A to design a larger RCT with a prenatal and postnatal intervention. The protocol has been revised to include subobjectives 3A and 3B. The study protocol has been submitted to the IRB and is pending approval. The MOP has been developed. Five research team members have completed the Certified Lactation Course training. Curriculum has been developed for the antenatal colostrum expression guidelines and the lactation education curriculum. The educational video for the ABME is currently being edited and the video for lactation support will be created by end of July 2025. In regards to Sub-objective 1A includes a RCT, the Level Up study, in adolescents with elevated body weight to determine the effects of exercise and dietary quality on cardiometabolic health. Intervention arms have been established, and the IRB protocol has been approved. Recruitment in underway. Under Sub-objective 1B takes advantage of the Level Up study to determine the impact of the intervention on substrate handling and energy expenditure. The usage of continuous glucose monitoring is approved by IRB. A newly recruited faculty is currently performing methodological studies for the usage of stable isotopes to determine carbohydrate and lipid oxidation rates. Under Sub-objective 1C also takes advantage of the Level Up study to determine the impact of the intervention on sleep duration and quality. The validation study in collaboration with the Arkansas Children’s Sleep Clinic is ongoing. Under Sub-objective 2A determines if early development factors, specifically physical fitness, sleep, and dietary quality, can predict the trajectory of cardiometabolic health. Studies are ongoing. All prepubertal visits have been completed. We are now recalling children for visits during adolescence. Sub-objective 2B originally planned to utilize a mouse model, will use a rat model of High-Capacity Runners (HCR) and Low-Capacity Runners (LCR) as planned under Sub-objective 3A, to more efficiently make use of resources while also offering advantages for muscle tissue analyses. Under a combined framework and IACUC protocol, a comprehensive set of metabolic phenotyping and DEXA data will be collected. Sub-objective 3A (and 2B) - IACUC protocol approved July 2025. Sub-objective 3B - to assess the effectiveness of a physical in preschool-age children of mothers with elevated body weight. IRB approval is obtained, 14 parent-child dyads were enrolled, and delivery of the intervention sessions have begun. Manuscripts summarizing the findings of the pilot and protocol are in preparation. 6026-10700-001-022S: Objective 1 continued to investigate how parental diet quality and metabolic status during critical windows of development programs offspring cardiometabolic health. Sub-Objective 1A - IACUC protocol is approved. Experiments have been combined for the Sub-Objective 1B and 1C fruit and vegetable consumption studies to reduce the total number of animals needed and the IACUC protocol was approved. Freeze-dried fruits and vegetables have been sent off for proximate analysis. Four manuscripts were published. Objective 2 continued to identify specific mechanisms by which prenatal and postnatal fruit and vegetable (FV) consumption program musculoskeletal development. In Sub-Objective 2A, researchers are expanding bone-specific knockout mouse colonies for our high-fat diet breeding studies that will begin in the coming months. Researchers received IACUC approval for breeding for studies proposed in Sub-Objective 2B. Objective 2C - to reduce animal usage, researchers have decided to collect muscle samples from the combined experiment in Sub-objective 1B/1C. One manuscript was published and an additional manuscript is expected to be published in the coming months. In regards to Objective 3 continues determining whether introductory fruits and vegetables interact with microbially derived butyrate to promote gut barrier function using in vitro and in vivo methods. Researchers digested commercial fruit and vegetable baby food purees and are working to mimic how bacteria break them down in the large intestine. Further work is being carried out to ensure proper regulatory oversight is in place for investigating how the dietary addition of fruits and vegetables influence gut barrier function in rodent models that do not have any gut bacteria or that are bred to be without key signaling proteins for gut barrier protection. One review manuscript and one original research manuscript have been published.

Accomplishments
1. Childhood cardiometabolic risk factors associated with the perinatal environment of the maternal-paternal-child triad. Researchers in Little Rock, Arkansas, have revealed positive association between excessive weight gain during pregnancy and child body fat at age 2 years, independent of pre-pregnancy body mass index at conception. Participants that had excessive weight gain during their first pregnancy were also more likely to have similar weight gain in following pregnancies. Further studies demonstrated that paternal body fat, cholesterol and lipids as well as dietary intake of added sugar were associated with higher risk for children presenting with 2 or more cardiometabolic risk factors at age 5 years. These findings suggest that dietary and exercise interventions before pregnancy targeting parental adiposity and dyslipidemia, and dietary habits during pregnancy could improve child’s health later in life.

2. Maternal immune cell gene expressions are associated with maternal gut microbiome, milk composition and infant gut microbiome. Overweight in women of childbearing age is a risk factor for mothers during pregnancy and predisposes babies to obesity, cardiovascular diseases, type 2 diabetes, impaired cognition, and allergies. Limited information was available on the association of immune cell gene expression with factors such as maternal milk components, gut microbiota, and dietary components, as well as with the infant's fecal microbiota. The results of this study showed that the immune cell genes have a robust association with maternal dietary components, milk components, and both the mothers and infants gut microbiota, suggesting complex yet important interconnections. A deeper understanding of this association may aid in developing effective strategies against obesity-mediated effects on both mothers and their infants.

3. PFAS exposure during pregnancy is associated with maternal cardiometabolic outcomes during pregnancy and sex-specific effects on placental development. To better understand the relationship between organic pollutants exposure during pregnancy, cardiometabolic health outcomes and placental development, researchers evaluated the outcomes of 285 participants. PFAS levels were negatively associated with lipids, cholesterol and pulse during pregnancy and positively associated with blood pressure. These findings suggest that organic pollutant exposure during pregnancy influence maternal health and cardiometabolic outcomes. Further, ARS researchers in Little Rock,Arkansas explored the effects of organic pollutants on gestational age acceleration during pregnancy and revealed that placental development responded differently to organic pollutants by fetal sex. Male placenta experienced a more stunted development whereas female placenta had increased gestational age acceleration, which may be due to an increase in developmental maturation in the face of environmental adversity.

4. Infant gut microbes and milk oligosaccharides can shape metabolite production and immune response in mice, independently and synergistically.. Early life gut microbiota establishment is critical for optimal immune response and long-term infant health. Bifidobacterium infantis (B.infantis), a major microbe found in breast-fed infants, is highly abundant in early life of the infant gut. However, the benefits of this microbe to early life mucosal and systemic immune system development have not been well explored. Using a preclinical model, ARS researchers in Little Rock,Arkansas demonstrated that early-life colonization with B. infantis results in higher levels of short-chain fatty acids and induces tryptophan metabolism, which are well-established to play a crucial role in the immune response. These changes were accompanied by an increase in the immune cells in the lymphoid tissue. Addition of human milk bioactives (oligosaccharides) with B. infantis increased the immunoglobulin A (IgA) and G (IgG) in the blood. These findings further elucidate the mechanism by which B. infantis promotes immunomodulatory effect during early life.

5. Dietary soy protein reverses weight-related fatty liver. ARS researchers in Little Rock,Arkansas found that soy protein intake can help reverse fatty liver disease caused by obesity in rats. In this study, the improvement occurred regardless of the soy's isoflavone content, suggesting that soy protein itself plays a key role. The study also noted changes in the rats' gut bacteria, indicating a link between diet, liver health, and gut microbiota. Incorporating soy protein into the diet may offer a natural approach to improving liver health in obesity-related conditions, which has to be tested in humans.

6. Microbes matter: exploring the connection between infant gut microbiota and bone development. Human milk is considered a good source of nutrition for infants and is thought to be necessary for bone and skeletal development. Maternal secretor status, the ability to secrete blood group antigens in bodily fluids, is one factor in human milk that can influence the concentration and percentage of different gut bacteria. To investigate, infant gut bacteria that consumed secretor or non-secretor mothers’ milk or cow's milk formula, young mice were given the different gut microbiota and the effect on bone development was investigated. Mice receiving gut bacteria from milk formula fed infants showed lower bone growth and development than in control mice or mice given gut bacteria from human milk (both secretor and non-secretors mothers) fed infants. Results from this study suggest that milk formula feeding for infants may not be optimal for bone growth and development.

7. The effect of diet on the brain development in healthy infants throughout the first year of life. ARS researchers in Little Rock,Arkansas explored how different infant diets affect brain development during the first year of life. Using electroencephalogram (EEG) technology, they monitored the brain activity of approximately 500 healthy infants receiving human milk or commercially available dairy-based infant formula, or soy-based formula at 3, 6, 9, and 12 months of age. Scientists focused on EEG microstates which are brief patterns of brain activity that reflect how the brain processes information. They observed that, regardless of diet, these microstates evolved as expected with age, indicating normal brain development. Importantly, there were few significant differences between the diet groups, suggesting that formula feeding does not negatively impact early brain function. This study indicates that both human milk and infant formula support healthy brain development in infants.

8. Maternal microbiome and metabolome were potential predictors of low-birth-weight infant. Low birth weight (babies born at less than 2,500 grams) affects approximately 15 to 20 percent of global births annually and is associated with poor child development. Researchers leveraged stool samples from pregnant women from Guatemala that are part of the Women First Clinical Trial from the University of Colorado to better understand how the maternal gut microbiome and circulating metabolites may predict risk of low-birth-weight infants. Results indicated that less beneficial gut microbes and circulating metabolites of the mother are associated with low-birth-weight infants compared to normal weight infants. As well as provided potential evidence that the mother's microbiome during pregnancy could be used to predict if they were going to have a low birth weight compared to normal birthweight infant. Overall, these findings highlight the need for future research that can target more specific functional and predictive roles of the maternal gut microbiome in infant birth outcomes, such as birthweight.

9. Feeding human milk beyond early developmental stages supports adequate growth, development, and nutritional intake. To better understand the relationship between human milk feeding for longer than 1 year and toddler growth, development and dietary intake, ARS researchers in Little Rock,Arkansas evaluated the outcomes of 185 women-child pairs enrolled in a longitudinal study. Children receiving human milk beyond 1 year had lower weight and ate more fruits and seafood with no impact on developmental testing. These results strengthen evidence that BBI supports adequate childhood growth, nutritional status, and development.

10. Single-cell transcriptomics reveals that human milk feeding shapes neonatal immune cell interleukin signaling pathways in a nonrandomized clinical trial . Several epidemiological studies support human milk feeding (HMF) benefits in comparison to formula feeding (FF), that include lower rates of upper respiratory tract and gastrointestinal tract infections, necrotizing enterocolitis during infancy and reduced risk of allergy, and decreased incidence of obesity in childhood. However, the mechanism of human milk contributes to the development of the infant’s innate and adaptive immune function is still unknown. Thus, the effects of human milk vs formula on the ontogeny of the systemic immune system in healthy newborn infants were investigated. Data demonstrated that human milk feeding shapes cell signaling pathways in peripheral immune cell subsets that are likely linked to lower allergic inflammation and infection.

11. Association between body composition, fitness, and physical activity with postural balance in children. ARS researchers in Little Rock,Arkansas found that body composition in children, fitness, and physical activity levels are linked to their balance. Specifically, higher levels of physical fitness and activity were associated with better postural control, even in children with higher fat mass. This suggests that encouraging regular physical activity can help improve balance in children, regardless of their body weight. These findings highlight the importance of promoting fitness and active lifestyles to support children's physical development and coordination.

12. Stress during lactation can impact offspring's bone health. A high fat diet and during pregnancy led to differences in gut microbiome of offspring analyzed by biological sex, providing insight into how diet during pregnancy programs offspring microbiome and metabolic health. Further, researchers identified a number of microbial metabolites of dietary phenolic acids, which appeared to suppress bone resorption in a mouse model of menopausal osteoporosis. Finally, a novel class of cyclopropane fatty acids (CpFAs) generated from bacterial metabolism of foods were identified in porcine rectal content and blood, providing new insights into how microbes alter lipid components in our food leading to the production of potentially bioactive metabolites.

13. Impact of diet on offspring gut microbiota, bone loss, and lipid metabolism in pre-clinical models.. A high fat diet and during pregnancy led to differences in gut microbiome of offspring analyzed by biological sex, providing insight into how diet during pregnancy programs offspring microbiome and metabolic health. Further, researchers identified a number of microbial metabolites of dietary phenolic acids, which appeared to suppress bone resorption in a mouse model of menopausal osteoporosis. Finally, a novel class of cyclopropane fatty acids (CpFAs) generated from bacterial metabolism of foods were identified in porcine rectal content and blood, providing new insights into how microbes alter lipid components in our food leading to the production of potentially bioactive metabolites.

14. Milk microRNAs have a minimal impact on the milk oligosaccharides-induced growth of Bifidobacterium infantis. Human milk components shape the infant gut microbiota composition and function. Small RNAs, known as microRNA (miRNAs), are abundant but understudied bioactive molecules present in human milk. To determine how milk miRNAs regulate the growth of the most common infant gut microbiota, Bifidobacterium infantis, we grew this bacterium in two substrates (lactose and human milk oligosaccharides, HMOs) with or without the miRNAs. Our findings showed that HMOs significantly promoted the growth of B. infantis with minimal effect of miRNAs. Gene expression related to HMOs metabolism was also increased when HMOs were used as the growth substrate, with an insignificant effect of miRNAs. These findings demonstrated that HMOs are the major contributing factor to the infant microbial growth and function, and miRNAs provide minimal contribution.

15. Maternal Undernutrition Exacerbates Effects of Ambient Heat during Pregnancy in Mice. There is emerging evidence that rising outdoor temperatures can be harmful to both mother and infant health. Also, poor dietary intake (decreased intake of micronutrients) of the mother in addition to heat stress can lead to reduced growth of the baby. Researchers designed an animal model to look at the interaction of modest heat and reduced micronutrient intake during pregnancy to determine changes in placental and fetal development. Investigators found reduced growth of the placenta and fetus when exposed to the combination of heat and poor nutrition. The dams (moms) exposed to heat and or heat plus poor nutrition showed alterations to placenta gene expression (the organ that provides nutrients and oxygen to the baby during pregnancy) related to nutrient transport, growth of blood vessels, and stress-related responses (i.e. inflammation and endoplasmic reticulum stress). Combined these results point to an interaction between modest heat and micronutrient depletion on placental dysfunction and the development of fetal growth restriction, highlighting the emerging link of maternal nutrition and heat stress typically seen in resource-restrained settings.

16. Housing temperature alters burn-induced hypermetabolism and augments energy expenditure in mice. Researchers found that housing mice at ambient temperatures which are typically colder than thermoneutrality (temperature where there is no additional energy needed to maintain stable body temperature) led to increases in energy expenditure and altered adipose tissue. Burn injuries led to greater energy expenditure at ambient temperature that was reduced in females and absent in males housed at thermoneutrality. Researchers also found that when these mice were administered a protonophore (a drug that pokes holes in mitochondrial membranes), while their energy expenditure increased, the increase in energy expenditure was less when housed at thermoneutrality compared to colder ambient temperatures. These studies highlight the importance of factoring in house temperature when using rodent models to study anti-obesity treatments that target lowering energy expenditure.

17. Dietary prevention of antibiotic-induced dysbiosis and mortality upon aging in mice. Oral antibiotic results in loss of diversity of the gut microbiome which has association to increased risk for age-related diseases. Using a mouse model with different kinds of diets and oral antibiotics on the gut microbiome and health in older mice were investigated. Antibiotic usage with high glycemic diet induced the gut microbiome dysbiosis, gastrointestinal disease, and sudden death. In contrast, a low glycemic index diet had less perturbation to the microbiome and a regular lifespan. Also, Bacteroides and activation of bile acid pathway protected mice from the negative effects of antibiotics.

18. Calorie restriction during pregnancy impacts the maternal and offspring fecal microbiome and is associated with offspring growth outcomes. Maternal undernutrition is the most common global cause of poor fetal growth which in turn leads to worse outcomes for babies. Researchers from ARS Little Rock, used a mouse model of maternal caloric restriction during pregnancy to test the role of the maternal and early life fecal microbiome in offspring growth. Results showed that caloric restricted moms and their offspring had reduced levels of beneficial gut microbes. Associations with different microbes from the mother and/or offspring gut microbiome with weight gain during pregnancy, litter size, and offspring weight outcomes were observed. These findings highlight the potential role of maternal diet and gut microbiome on offspring growth outcomes. Future studies are still needed for a more complete understanding of the role of gut bacteria in pregnancy and infancy and how they impact offspring long-term health.

19. The association between hepatic steatosis, vitamin D status, and insulin resistance in adolescents with elevated body weight.. In a six-month study in 44 adolescents, scientists found that low or declining vitamin D levels were associated with worsened insulin resistance, especially in population subgroups with higher liver fat, as measured by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). The triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL) showed a similar trend across all ethnic groups; suggesting liver fat and race or ethnicity may influence how vitamin D impacts metabolic health. These findings offer a potential explanation for inconsistent results in prior studies and suggest that liver fat and racial or ethnic background should be considered when evaluating vitamin D’s role in insulin resistance. Future research should explore tailored prevention strategies for adolescents at risk.

20. Human milk metals and metalloids shape infant microbiota. Metals and gut microbes (i.e., microbiota) have historically co-evolved. Early in life human milk metals may influence infant gut microbiota composition and health outcomes. In an independent cross-sectional analysis of mother-infant pairs from two separate time-points, significant variations in metals concentrations and microbial abundances were observed. In the mature lactation stage, seven significant correlations between metals and microbiota were identified. Notably, correlation analyses indicated a higher abundance of the Streptococcus genus when manganese (Mn) and vandium concentrations were lower. This study highlights the significance of metal microbiota interactions in early infant development. Mn may be the most potential metal to influence microbiota, and Streptococcus to potentially be the most influenced genus by metals with the infant gut microbiota.

21. Dyslipidemia, high blood pressure, and aerobic capacity associate with platelet mitochondria function in children – The Arkansas Active Kids study. Platelets play a key role in stroke and heart attacks and are now recognized as contributors to atherosclerosis. Although platelets lack a nucleus, their function may depend on mitochondrial health. This study evaluated the relationship between platelet mitochondrial function and cardiovascular health markers in children aged 7 to 10 years. They found that high blood pressure and body fat were associated with increased platelet mitochondrial respiration, while elevated LDL cholesterol and low aerobic fitness reduced the ability of platelets to increase oxygen consumption under stress. These findings suggest that traditional cardiovascular risk factors influence platelet mitochondrial function in children.

22. Fermented foods and maternal health during pregnancy and infant health during the first 1,000 days of life. Fermented foods (FF) are getting more attention than ever due to their nutritional value. FF are an excellent source of prebiotics (promotes growth of beneficial microbes), probiotics (beneficial microbes) and postbiotics (health-promoting byproducts of microbes). In this review article, scientists from ARS discussed the health benefits of FF in maternal and child health, especially during pregnancy and the first 1,000 days of life. Existing knowledge gap and future studies to provide evidence-based mechanistic insights into the benefits of FF were discussed.

23. Platelets Modulate Leukocyte Population Composition Within Perivascular Adipose Tissue. A Western diet high in fat, sugar and salt altered the composition of both the perivascular adipose depots by altering the function of immune cell populations, as well as influencing the distribution of immune cells present in perivascular adipose tissue. This shift in leukocyte populations suggests an overall phenotypic switch towards a more pro-inflammatory and thus vasoconstrictive environment.

24. Methodology to predict fitness in children. Scientists examined whether a simplified measure of physical fitness in children, known as the oxygen uptake efficiency slope (OUES), could reliably estimate their peak oxygen uptake (VO2peak), a key indicator of cardiovascular health. The Scientists tested 94 children aged 7-10 years using a stationary bike and found that OUES did not accurately predict VO2peak, even when using data from the full test or just the early stages. This suggests that while OUES is easier to obtain, it may not be a dependable substitute for full fitness testing in children. The findings emphasize the importance of comprehensive assessments when evaluating children's heart and lung fitness, findings that will contribute to improving pediatric health evaluations.

25. Characterization of how colonocyte substrate utilization impacts cellular mechanism supporting colonic health. We reviewed the current literature on how colon epithelial cells can switch metabolic fuel utilization to signal changes in gut barrier function via a mechanism related to cellular hypoxia. We detailed how these mechanisms are described in adult populations, but are not mature in infants that are fed exclusively with human milk. We propose that immune signaling can modulate colonocyte energy substrate utilization to assist immune cell trafficking across the gut barrier.

26. Protective effects of sulforaphane preventing inflammation and oxidative stress to enhance metabolic health. Scientists in ARS Little Rock,Arkansas and their collaborators performed a literature review to determine potential health benefits of sulforaphane, a natural compound found in cruciferous vegetables like broccoli. Their publication discusses how sulforaphane may help reduce inflammation and oxidative stress, factors linked to metabolic diseases such as type 2 diabetes. By activating the Nrf2 pathway, sulforaphane supports the body's defense mechanisms against cellular damage. They note that more clinical research is needed to fully understand its effects across different age groups.

Review Publications
Fiecke, C., Crimmins, M., Hameed, A., Sims, C., Williams, D., Bode, L., Martinez, A., Andres, A., Ferruzzi, M. 2024. Dietary modulation of human milk bioactives is associated with maternal FUT2 secretor phenotype: An exploratory analysis of carotenoids and polyphenol metabolites. Frontiers in Nutrition. 11(2024):Article 1463969. https://doi.org/10.3389/fnut.2024.1463969.
Corken, A., Weinkopff, T., Wahl, E.C., Sikes, J.D., Thakali, K.M. 2025. Platelets modulate leukocyte population composition within perivascular adipose tissue. International Journal of Molecular Sciences. 26(4):1625. https://doi.org/10.3390/ijms26041625.
Diniz-Sousa, F., Edwards, T., Diaz, E., Weber, J.L., Børsheim, E. 2025. The associations of body composition, fitness, and physical activity with balance in children: The Arkansas Active Kids study. Gait and Posture. 118:61-68. https://doi.org/10.1016/j.gaitpost.2025.01.081.
Assress, H.A., Ferruzi, M.G., Hameed, A., Pack, L.M., Lan, R.S. 2025. Evaluation of ion source parameters and liquid chromatography methods for plasma untargeted metabolomics using orbitrap mass spectrometer. Journal of Chromatography B. 1257:124564. https://doi.org/10.1016/j.jchromb.2025.124564.
Tas, E., Flint, A., Libman, I., Muzumdar, R., Ou, X., Williams, D.K., Borsheim, E., Diaz, E. 2025. The association between hepatic steatosis, vitamin D status, and insulin resistance in adolescents with obesity. Obesity Pillars. 14(2025):100173. https://doi.org/10.1016/j.obpill.2025.100173.
Kaufmann, Y., Williams, R., Cotter, M., Ferrando, A., Børsheim, E. 2025. A comparison of derivatives of alanine and d-alanine used in gas chromatography-mass spectrometry analysis for protein kinetics. Journal of Proteome Research. 24(4). https://doi.org/10.1021/acs.jproteome.4c01004.
Na, X., Mackean, P.P., Cape, G.A., Johnson, J.W., Ou, X. 2024. Maternal nutrition during pregnancy and offspring brain development: insights from neuroimaging. Nutrients. 16:3337. https://doi.org/10.3390/nu16193337.
Huang, Y., Glasier, C.M., Na, X., Ou, X. 2025. White matter functional networks in the developing brain. Frontiers in Neuroscience. 18(2025):1-9. https://doi.org/10.3389/fnins.2024.1467446.
Paz, H., Buddha, L., Zhong, Y., Sikes, J.D., Wankhade, U.D. 2024. Impact of maternal high-fat diet on offspring gut microbiota during short-term high-fat diet exposure in mice. Physiological Reports. 12(21):e70111. https://doi.org/10.14814/phy2.70111.
Hakkak, R., Korourian, S., Li, W., Spray, B., Twaddle, N., Randolph, C., Børsheim, E., Robeson, .S. 2024. Dietary soy protein reverses obesity-induced liver steatosis and alters fecal microbial composition independent of isoflavone level. Frontiers in Nutrition. 11(2024):1487859. https://doi.org/10.3389/fnut.2024.1487859.
Mccorkle, G., Andres, A., Sims, C.R., Casey, P.H., Sorensen,, S.T., Durey, T., Bellando, J. 2024. Exploring the relationship between child temperament, maternal psychiatric symptoms, family environment and infant feeding. Maternal and Child Nutrition. 21(1).Article e13728. https://doi.org/10.1111/mcn.13728.
Corken, A., Wahl, E.C., Sikes, J.D., Thakali, K.M. 2024. Western Diet Modifies Platelet Activation Profiles in Male Mice. International Journal of Molecular Sciences. 25(15):8019. https://doi.org/10.3390/ijms25158019.
Tripp, P., Davis, E.C., Gurung, M., Rosa, F., Bode, L., Fox, R., Leroith, T., Simecka, C., Seppo, A., Järvinen-Seppo, K.M., Yeruva, V. 2024. Infant microbiota communities and HMO supplementation independently and synergistically shape metabolite production and immune responses in healthy mice. Journal of Nutrition. 154(2024):2871-2886.
Ruebel, M., Gillie, S.P., Yeruva, V., Tang, M., Frank, D.N., Garcés, A., Figueroa, L., Lan, R.S., Assress, H., Kemp, J.F., Westcott, J., Hambidge, K., Shankar, K., Krebs, N.F. 2024. Associations between maternal microbiome, metabolome and incidence of low-birth weight in Guatemalan participants from Women First Trial. Frontiers in Microbiology. 15(2024).Article 1456087. https://doi.org/10.3389/fmicb.2024.1456087.
Smith, K.M., Francisco, S.G., Zhu, Y., Leroith, T., Davis, M.L., Crott, J.W., Barger, K., Greenberg, A.S., Smith, D.E., Taylor, A., Yeruva, V., Shledon, R. 2024. Dietary prevention of antibiotic-induced dysbiosis and mortality upon aging in mice. Journal of Federation of American Societies for Experimental Biology. 38(23).Article e70241. https://doi.org/10.1096/fj.202402262R.
Sobhi, H.F., Mercer, K.E., Lan, R.S., Yeruva, V., Ten Have, G.A., Deutz, N.E., Piccolo, B.D., Adams, S.S. 2024. Novel odd-chain cyclopropane fatty acids: detection in the mammalian lipidome and uptake by hepatosplanchnic tissues. Journal of Lipid Research. 65(10).Article 100632. https://doi.org/10.1016/j.jlr.2024.100632.
Salinas, M.L., Mulakala, B.K., Davidson, L.A., Cai, J.J., Donovan, S.M., Chapkin, R.S., Yeruva, V. 2025. Single-cell transcriptomics reveals that human milk feeding shapes neonatal immune cell interleukin signaling pathways in a nonrandomized clinical trial. The American Journal of Clinical Nutrition. https://doi.org/10.1016/j.ajcnut.2025.04.024.
Yao, T., Tuncil, Y.E., Bhattarai, S., Gurung, M., Bode, L., Yeruva, V., Lindemann, S.R. 2025. Effect of maternal miRNAs and milk oligosaccharides on regulating the growth behavior of Bifidobacterium longum subspecies infantis. Journal of Functional Foods. 128(2025):106800. https://doi.org/10.1016/j.jff.2025.106800.
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