Search Results (343)

Background/Objectives: Early-life gut colonization is crucial for immune system development and metabolic programming. Lactobacillus reuteri has been investigated for its capacity to modulate neonatal gut microbiota, but evidence regarding maternal supplementation during lactation remains limited. This study aimed to evaluate the effect of maternal supplementation with L. reuteri SGL 01 on the microbial composition of breast milk and neonatal feces over the first month of life. Methods: This is an exploratory, prospective, open-label randomized clinical trial. Lactating mothers of full-term and exclusively breastfed infants were randomized to receive either daily L. reuteri SGL 01 (1 × 10⁹ CFU) for 30 days or no supplementation. Quantitative real-time PCR was used to assess Bifidobacterium spp., Lactobacillus spp., Clostridium spp., and the Bacteroides fragilis group in maternal milk and neonatal feces at baseline (T0) and after 30 days (T1). Results: Twenty-seven mother–infant dyads completed the study (15 supplemented, 12 controls). No significant changes in breast milk microbiota composition were observed across any of the bacterial taxa following maternal supplementation. In contrast, neonatal fecal samples from the supplemented group showed significant increases in Bifidobacterium spp. (p < 0.001), Lactobacillus spp. (p = 0.029), and Clostridium spp. (p = 0.003) at T1. No significant microbial changes were observed in the control group, except for a slight reduction in Clostridium spp. (p = 0.046). Conclusions: Maternal supplementation with L. reuteri SGL 01 did not modify breast milk microbiota but was associated with a modulation of neonatal gut colonization, including an increased abundance of beneficial taxa such as Bifidobacterium, suggesting potential indirect maternal-to-infant microbial effects. Full article

The excessive use of phytosanitary products represents a growing concern, due to their persistence and potential environmental and toxicological impacts. Among these compounds, glyphosate, a glycine-derived chemical marketed as a broad-spectrum herbicide, is one of the most widely used pesticides worldwide. Breast milk is a complex biological matrix that can reflect environmental exposure, making it highly suitable for assessing glyphosate contamination. This study aimed to demonstrate a screening method to determine glyphosate concentrations in the breast milk of 100 postpartum women residing in Tupã, São Paulo, Brazil—90 in urban areas and 10 in rural areas—using high-performance liquid chromatography (HPLC) for rapid detection. By validation parameters, it was possible to verify, through the correlation coefficient (r), that the method is linear within the working range; the LD was 0.14 mg/L and the LQ was 0.43 mg/L. The recovery obtained by standard sample fortification was 92%. All analyzed samples presented detectable levels of glyphosate, indicating consistent exposure patterns and suggesting relevant environmental contamination routes in the region. These findings provide evidence of glyphosate presence in human milk and reinforce the importance of continuous monitoring strategies and preventive public health measures aimed at reducing exposure to agricultural contaminants. Full article

Background: Based on our extensive cohort study, the Maternal Nutrition and Infant Investigation (MUAI), this research investigated the associations between human milk oligosaccharide (HMO) intake during the postnatal period and allergic disease development and gut microbiome composition in early childhood through long-term follow-up. Methods: Human breast milk (HBM) samples at five lactation stages and fecal samples of infants and young children were collected. Children aged 5 years included in this study were categorized into allergic and non-allergic groups via standardized allergen testing. Results: The findings indicated that higher HMO intake levels across five distinct lactation periods may be linked to a reduced incidence of allergies in children. The consumption of six major structurally representative HMOs was significantly associated with alterations in the gut microbiota profiles of young children. Moreover, there were notable differences in gut microbiota composition between allergic and non-allergic children. Specifically, beneficial bacteria such as Bifidobacterium, Akkermansia, and Ruminococcus were significantly enriched, in addition to the levels of metabolite propionic acid, a beneficial short-chain fatty acid, which were notably higher in the non-allergic group. To further validate the relationship between Bifidobacterium abundance and early HMO intake, the analysis revealed that a differential strain biomarker, Bifidobacterium adolescentis (B. adolescentis), exhibited significant correlations with specific HMOs at different lactation stages, particularly showing a strong positive correlation with 2′-fucosyllactose (2′-FL) content. Conclusions: These findings suggest that early-life HMO intake is associated with long-term differences in allergic outcomes, potentially through modulation of gut microbiota composition, particularly the enrichment of B. adolescentis. Full article

Breast cancer is the most common and deadliest cancer among women. While overexpression of specific markers guides disease stratification and has enabled the development of targeted therapies, identifying new therapeutic targets remains critical, particularly for aggressive subtypes lacking effective treatments. This study evaluated the expression of α-Lactalbumin (LALBA) and nucleolin (NCL) in breast cancer tissues from Mexican patients using gene expression analysis and immunohistochemistry. LALBA, a major milk protein normally expressed only during late pregnancy and lactation, was detected in nearly all tumor samples and showed higher levels in aggressive subtypes, with overexpression displaying a slight trend toward poorer overall survival. NCL, a multifunctional nucleolar protein, exhibited predominantly nuclear localization, with moderate expression associated with improved survival. Both proteins correlated with tumor immune features, including increased tumor-infiltrating lymphocytes (TILs) and PD-L1 expression for LALBA, and elevated CD8⁺ T cells, PD-L1, and TIM-3 expression for NCL. Overall, these findings suggest that LALBA and NCL are associated with tumor aggressiveness, immune context, and survival trends in breast cancer. Additional studies in larger cohorts are needed to define their clinical relevance. Full article

Background: Exposure to environmental pollutants, especially endocrine-disrupting chemicals, disproportionately affects vulnerable populations like pregnant women, lactating mothers, and preterm infants. This study aimed to assess the detection patterns of DiNP-, DEP-, and DEHP-related metabolites in maternal urine and breast milk, examine agreement between matrices, and explore maternal factors associated with phthalate exposure. Methods: Fifty-five mothers who delivered at ≤32 gestational weeks and whose infants were hospitalized in the Neonatal Intensive Care Unit (NICU) were enrolled. Breast milk and urine samples were analyzed using a validated isotope-dilution LC–MS/MS method. Urinary phthalate metabolite concentrations were adjusted for specific gravity. Linear mixed-effects models with a random intercept for mother were used to examine associations between urinary and breast milk phthalate metabolite concentrations, assess temporal changes, and evaluate the influence of breast milk lipid content. Results: DEHP and DiNP metabolites were detected in nearly all maternal urine samples. Breast milk contained predominantly primary metabolites (MEHP and MiNP), while secondary oxidative metabolites were rarely detected. Urine concentrations consistently exceeded breast milk concentrations. Urinary and breast milk phthalate concentrations were not correlated across sampling periods, indicating limited matrix concordance. Conclusions: Mothers of very preterm infants experience sustained phthalate exposure in the postpartum period; however, limited metabolite transfer to breast milk indicates that maternal urine remains the preferred biomonitoring matrix for assessing systemic phthalate exposure. Breast milk phthalate profiles exhibit compound-specific temporal changes and appear largely independent of concurrent urinary exposure biomarkers. Full article

Background/Objectives: This study systematically analyzed the concentration dynamics of human milk oligosaccharides (HMOs) and the distribution characteristics of secretory (Se) and Lewis (Le) phenotypes in China. Methods: A total of 1462 breast milk samples were collected from lactating mothers in six major regions of China, including Changchun, Lanzhou, Chengdu, Tianjin, Guangzhou, and Shanghai. We quantified 17 major HMOs by high-performance anion exchange chromatography-pulsed amperometric detection (HPAEC-PAD), and Se/Le phenotypes were determined to evaluate regional differences and distribution patterns. Results: Total HMO concentration in breast milk showed a significant downward trend within 200 days postpartum and stabilized after 200 to 400 days. Fucosylated HMOs accounted for the highest proportion $60.0–83.0\%$, among which 2′-FL had the largest concentration $903.4–2832.7 \mathrm{m}\mathrm{g}/\mathrm{L}$; acetylated HMOs $8.4–17.6\%$ and sialylated HMOs $8.2–25.3\%$ accounted for relatively lower proportions. This study further divided breast milk into four phenotypes based on HMO characteristics: 72.49% of the samples were Se+/Le+, 6.145% were Se+/Le−, 20.12% were Se−/Le+, and 1.24% were double negative (Se−/Le−). Se+ and Le+ phenotypes accounted for 78.7% and 92.6% of the total population, respectively. The total concentration of HMOs in breast milk of different phenotypes was significantly different, with the average total HMO concentration of Se+/Le+ breast milk being the highest (8342 mg/L), while that of Se−/Le− breast milk being the lowest (4532 mg/L). Se+ phenotype was associated with higher levels of fucosylated HMOs, including 2′-fucosyllactose (2′-FL) and lacto-N-fucopentaose I (LNFP I), and lower levels of lacto-N-tetraose (LNT) and sialyl-lacto-N-tetraose b (LST b) compared to other phenotypes. Most HMOs reached their highest concentrations during the colostrum (CM) and transitional milk (TM) stages, followed by a progressive decline with lactation, with phenotype-specific variations evident across all HMOs. Notably, certain HMOs, such as 3-FL, 3′-SL, DFL, and LNDFH II, exhibited distinct temporal patterns. Conclusions: This study revealed the Se/Le phenotype distribution and dynamic characteristics of HMOs in the Chinese mother-infant population, offering a valuable reference for global breast milk composition databases and infant nutrition research. Full article

Introduction: Human breast milk (HBM) is a critical source of nourishment for newborns, containing bioactive compounds that influence infant growth and metabolic programming. Among these compounds, leptin—a hormone primarily produced by adipocytes but also synthesized in the mammary gland—has gathered attention for its potential role in regulating energy balance and body weight. This study investigates the influence of maternal factors on HBM leptin concentrations and explores their associations with neonatal growth parameters. Material and Methods: 262 HBM samples were collected from healthy lactating mothers through Spanish Biobanks during the first six months postpartum. Data on maternal characteristics (body mass index (BMI), age, physical activity, parity, and delivery type) and neonatal measurements (weight, length, and head circumference) were collected. Leptin concentrations in skimmed HBM were measured using the ELISA technique (R&D Systems™, Minneapolis, MN, USA). Statistical analyses were conducted using R version 4.3.1 and MATLAB R2023a, with significance set at p < 0.05. Results: Leptin levels were highest in and declined over time, reaching a stable level after the first month of lactation. Preterm deliveries exhibited significantly higher leptin concentrations than term deliveries (0.42 vs. 0.07 ng/mL). Higher leptin levels were also observed in younger and primiparous mothers. Maternal BMI was positively associated with leptin concentration, with mothers who had elevated BMI showing higher levels than those with optimal BMI (0.36 vs. 0.05 ng/mL). Maternal physical activity was not associated with leptin concentrations in univariate analyses; although greater self-reported physical activity appeared associated with lower leptin concentrations in regression models, this finding should be interpreted cautiously and should not be considered evidence of an independent or consistent effect. Neonatal growth parameters (weight, length, and head circumference) were negatively correlated with HBM leptin concentrations. Conclusions: Our findings indicate that leptin levels in breast milk reflect both maternal metabolic status and neonatal characteristics and may represent a compensatory mechanism in preterm infants. HBM leptin levels are modulated by maternal BMI, age, parity, and delivery type, and are associated with neonatal growth parameters. Full article

Mastitis is a common mammary gland disease in mammals that severely impairs lactation function, with Staphylococcus aureus (S. aureus) being the primary pathogenic bacterium. However, the molecular mechanisms underlying S. aureus-induced mastitis in sheep remain incompletely elucidated. This study employed RNA sequencing (RNA-SEq) technology to systematically analyze the dynamic transcriptomic characteristics of mammary tissue in small-tailed sheep (SHT) after S. aureus infection, aiming to clarify the molecular regulatory mechanism of the host immune response and its relationship with the occurrence of mastitis. Twelve lactating STH were selected to establish an S. aureus-induced mastitis model. Blood, milk, and tissue samples were collected at 0, 24, 48, and 72 h post-infection (hpi). The infected sheep exhibited typical mastitis symptoms, including exacerbated breast swelling, reduced milk yield, elevated udder temperature, and darker, more viscous milk. Hematoxylin–eosin (HE) staining revealed significant pathological changes over time, such as stromal hyperplasia, extensive inflammatory cell infiltration, severe necrosis and sloughing of mammary epithelial cells, and compromised tissue integrity. RNA-Seq analysis identified 1299 differentially expressed genes (DEGs), among which 75 core genes maintained stable expression throughout the infection time (24 hpi, 48 hpi, and 72 hpi). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these DEGs were associated with metabolic processes, protein binding, Toll-like receptor signaling, and the NF-κB pathway. The PPI network analysis identified core hub genes including PTK2B, STAT3, and JAK1/3, providing critical evidence for therapeutic target screening. Furthermore, qPCR verification indicated that the expressions of innate immune receptors TLR2, TLR4, TLR7, and TLR10, as well as pro-inflammatory factors IL-1β, IL-16, TNF-α, type I interferon (IFN-α), and nuclear transcription factor NF-κB were significantly upregulated in a time-dependent manner (p < 0.05). In conclusion, this study delineated the dynamic response of ovine mammary tissue to S. aureus infection, systematically elucidated temporal gene expression patterns, and revealed the molecular mechanisms underlying the tissue’s initial defense against inflammatory challenges. Full article

This study analyzes global data on human exposure to pesticides, focusing on glyphosate, POPs, carbamates, and organophosphates, which are among the most widely used in agricultural and urban environments, providing an overview of global human contamination by these substances. Current research has increasingly focused on the unintended consequences of pesticide use, including food, water, and soil contamination, biodiversity loss (especially beneficial insects such as pollinators), and the growing evidence of adverse impacts on human health (neurological, reproductive, endocrine, and carcinogenic effects). Therefore, we compiled information from several existing studies that evaluated pesticide residues in human biological samples, specifically urine, blood, and breast milk, to assess the extent of exposure. The analysis takes a global perspective, highlighting the importance of monitoring exposure in countries that demonstrate exceptionally high pesticide use (in terms of absolute volume), such as Brazil, the United States, and China, which are among the largest global consumers. The data cover both contemporary pesticides, whose consumption is driven by intensive agriculture in these and other countries, and persistent legacy compounds (POPs) that continue to circulate in nature and accumulate in the human body decades after their ban in many countries. Globally, there is a wide disparity in global regulations, and many developing countries continue to use pesticides that have been banned or severely restricted in more developed nations. Finally, it provides a critical overview of global data on human pesticide contamination. The data reinforce the critical importance of establishing preventive initiatives and strengthening surveillance and monitoring systems to detect and control pesticide residues in human populations globally, ultimately aiming to mitigate the harms of chronic pesticide exposure to human health and well-being. Full article

Background/Objectives: Melatonin, produced by the placenta and pineal gland, regulates circadian timing and has antioxidant and immunomodulatory actions. After birth, neonatal secretion is low and its circadian pattern matures over months; evidence in preterm neonates is mixed. We longitudinally monitored morning blood melatonin from birth to 38 weeks’ postmenstrual age (PMA) in breast milk-fed preterm neonates, assessing differences by time of birth (day vs. night), PMA, and weight-for-gestational-age (WfGA). Methods: A prospective NICU cohort, conducted within the ProMote study. In total, 132 preterm neonates were recruited from 112 mothers. For infants ≥33 weeks’ GA, three samples were obtained: umbilical cord (available in 94; otherwise at the first NICU admission), day of life (DOL) 4–7, and DOL 10–14; for infants <33 weeks’ GA, an additional sample at 35–36 weeks’ PMA. Melatonin was measured by ELISA. Primary analyses used raw melatonin concentrations in linear mixed-effects models; sensitivity analyses checked robustness. Results: A final sample comprised 122 neonates. Concentrations were low to modest with wide between-neonate variation and no monotonic change across PMA. Mixed models showed no consistent differences by time of birth and no stable WfGA effect; occasional PMA-specific contrasts did not recur at adjacent time points. Umbilical cord concentrations were low, and gestational age at birth did not materially influence levels at a given PMA. Sensitivity analyses led to the same inference. Conclusions: In breast milk-fed preterm neonates, morning serum melatonin from 26–38 weeks’ PMA shows substantial individual variability without consistent differences by time of birth, PMA, or WfGA. Full article

Background: Women with gestational diabetes mellitus (GDM) are vulnerable to oxidative stress, yet limited data exist on the antioxidant potential of their breast milk. This study aimed to evaluate the antioxidant capacity and basic composition of colostrum in women with GDM compared to healthy controls, focusing on total antioxidant capacity (TAC) and enzymatic antioxidants: superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Methods: The study included 77 lactating mothers: 56 with gestational diabetes (15 managed with diet/exercise—GDM G1; 41 required insulin—GDM G2) and 21 healthy controls. Colostrum samples were collected on days 3–5 postpartum and analyzed for macronutrients and antioxidant enzymes. To enable comparisons across study groups and to explore associations with maternal characteristics, a range of statistical methods was applied. A taxonomic (classification) analysis was then performed using the predictors that best fit the data: study group membership, maternal hypothyroidism history (from the medical interview), and gestational weight gain. Results: TAC was significantly lower in the GDM G2 group compared to GDM G1 and controls (p = 0.001), with no differences in enzymatic antioxidants. The control group had the highest energy (p = 0.048) and dry matter content (p = 0.015), while protein, fat, and carbohydrate levels did not differ significantly. After dividing the study group into four clusters, based on maternal health factors, including GDM status and thyroid function, TAC levels differed significantly between clusters, with the highest values observed in Cluster 3 (healthy controls without thyroid dysfunction) and the lowest in Cluster 2 (GDM and hypothyroidism). Analysis of colostrum composition revealed significant differences in energy content (p = 0.047) and dry matter concentration (p = 0.011), while no significant differences were found in other macronutrients. Conclusions: Our findings suggest that maternal metabolic and endocrine conditions, such as GDM and thyroid dysfunction, may differentially influence the nutritional and functional properties of colostrum—particularly its antioxidant potential. Full article

Accessory breasts denote the formation of extra breast tissue along the milk line, and are known to be more prevalent among Black and Asian populations, affecting both genders. This first-ever study aimed to determine the genetic aetiology of accessory breasts in a multiplex family, where all female siblings present with bilateral accessory breasts. The study also ascertained secondary findings (SFs) responsible for comorbidities. Clinical data and saliva samples were obtained from all family members. Ultrasound and histopathology confirmed the diagnosis. Whole-exome sequencing was conducted on DNA samples obtained from the saliva, with variant calling conducted utilising the Sentieon workflow. Variant classification was based on American College of Medical Genetics and Genomics guidelines. After segregation analysis, 12 candidate genes emerged. Among these, PRSS50 and FANCC emerged as top candidates, being implicated in breast diseases. However, two variants in FANCC (c.360del; p.His120GlnfsTer24 and c.355_358del; p.Ser119IlefsTer24) were selected as the most probable causal variants because of the role of this gene in hereditary breast and ovarian cancer syndromes. The remaining ten genes were reported as potentially accounting for comorbidities segregating with accessory breasts. Reported SFs involve TTR and RYR1. In conclusion, pathogenic variants in FANCC cause familial accessory breasts. These novel observations impact pathophysiology, genetic counselling, and personalised medicine. Full article

Establishing the relative stability of the gastrointestinal microbiome after birth is a long and complex process, and it occurs under various influences. The human gut microbiome plays a crucial role in influencing an individual’s health and well-being across all stages of life. Breastfeeding, the introduction of solid food at a certain stage after birth, and the type of food largely determine the composition of the developing microbiome. The influence of probiotics on the early development of the microbiome is gaining increasing interest. The method of in vitro co-cultivation with probiotic strains provides a clearer picture of the influence of these microorganisms on the community and the functional changes that the infant’s microbiome undergoes. We used fecal samples to study this influence by conducting metagenomic sequencing to determine the composition of the microbiome and a series of cultivations to determine the absorption of various fibers and prebiotic sugars from breast milk. We found statistically significant differences in the absorption of prebiotic sugars isolated from breast milk, as well as better absorption of several substrates in the presence of a probiotic strain. Full article

Maternal overweight and obesity have reached global epidemic levels, altering metabolic adaptations during pregnancy and lactation. Beyond their well-known impact on gestational outcomes, elevated BMI profoundly influences the secretion of adipokines—hormones derived from adipose tissue that circulate in maternal blood and are secreted into breast milk—thereby directly linking maternal metabolism to offspring development. In this state-of-the-art narrative review, we synthesize current evidence on how maternal overweight and obesity shape concentrations of key adipokines (leptin, adiponectin, ghrelin, obestatin, and resistin) in serum, cord blood and breast milk. Excess maternal weight robustly increases leptin, while effects on adiponectin, ghrelin, obestatin, and resistin remain uncertain. To our knowledge, this is the first review to focus specifically on the impact of maternal overweight and obesity on adipokine alterations across both pregnancy and lactation. Future studies should apply standardized sampling and analytical protocols and use longitudinal designs including body composition assessments to clarify their role in maternal and child metabolic health. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) alters maternal metabolism during pregnancy and may impact the biochemical composition of breast milk. Given the critical role of human milk in early-life metabolic programming, identifying metabolic alterations in GDM milk and understanding the effects of insulin therapy has important implications for neonatal health. This study aims to investigate the metabolomic profile of transitional breast milk in mothers with gestational diabetes mellitus compared with healthy controls and to evaluate the impact of insulin therapy on milk metabolite composition. Methods: Breast milk samples were collected between postpartum days 10 and 15 from 80 mothers with GDM and 80 matched controls. Metabolomic profiling was performed using gas chromatography–mass spectrometry (GC–MS), and data were analyzed using multivariate and univariate statistical techniques including PCA, PLS–DA, logistic regression, and ROC analysis. Conclusions: A total of 133 metabolites were identified, and GDM mothers exhibited a distinct metabolomic signature characterized by significant alterations in carbohydrate, amino acid, and microbial-derived metabolites. In particular, galactinol, arabitol, and pyrogallol were significantly decreased, while α-ketoglutaric acid and citric acid were elevated in the GDM group. Insulin-treated mothers showed unique metabolic changes involving glycolytic intermediates (glycerone phosphoric acid), purine metabolism (xanthine), and oxidative pathways (isocitric acid, gluconic acid lactone). Multivariate models based on the top metabolites achieved moderate discriminatory performance (AUC = 0.68). GDM is associated with substantial metabolic changes in transitional breast milk, and insulin therapy appears to modulate these alterations further. These findings suggest that maternal metabolic status and its treatment can shape the neonatal nutritional environment, potentially influencing early metabolic programming. Full article