Search Results (380)

The gut microbiota (GM) has become a key mediator of host health, with dietary manipulations promising ways of modulating the microbiome. This review focuses on the role of dairy bioactive (DB) compounds as precision modulators of intestinal microecology, including the whey proteins (WPs), including lactoferrin (LF), α-lactalbumin (LA), β-lactoglobulin, lysozyme (LZ), lactoperoxidase, glycomacropeptide (GMP), milk oligosaccharides (MOs), and bioactive peptides (BPs). This review compiles the existing evidence illustrating their dual-action mechanism through direct prebiotic activity and the promotion of beneficial taxa (Bifidobacterium, Lactobacillus, Faecalibacterium), along with selective antimicrobial activity and pathogen suppression. These compounds improve intestinal barrier integrity through tight junction (TJ) protein regulation, regulating short-chain fatty acid production, and modulating immune signaling pathways. Clinical evidence shows significant benefits in metabolism and inflammation among various populations. However, individual responses vary according to host factors such as enterotypes, FUT2 genotype, and baseline microbiota composition, suggesting the need for personalized intervention strategies. This review addresses critical knowledge gaps in dose–response relationships, long-term efficacy, and mechanistic pathways and suggests future directions for precision nutrition. By modifying molecular mechanisms in clinical applications, we have identified DB compounds as promising candidates for targeted modulation of the microbiota to optimize health and disease management. The review also brings together molecular mechanistic and clinically implementable, personalized dietary strategies, which have not been fully captured by previous reviews. It pinpoints gaps in knowledge related to dose–response characterization, long-term trial design, and multi-omics stratification that collectively define a new precision nutrition framework. In this approach, dairy-based intervention is planned for each person based on their microbial, genetic, and metabolic characteristics. Full article

Human milk is widely recognised as the optimal source of nutrition for newborns and infants, providing not only an ideal macronutrient composition but also a range of bioactive components that exert important non-nutritional functions, and as such it represents the first functional food consumed in early life. Among these bioactive components, the human milk oligosaccharides (HMOs)—a structurally diverse family of glycans present in human milk at concentrations 100- to 1000-fold higher than in the milk of other mammalian species—have emerged as multifunctional contributors to the establishment of the intestinal microbiome, immune development, anti-infective defence, and epithelial barrier integrity during a developmental window characterised by immune immaturity. The aim of the present narrative review is to synthesise current evidence on the anti-infective properties of HMOs in infancy and to integrate, within a single framework, five interconnected mechanisms through which HMOs protect the infant against infection: glycan-mimicry-based competitive inhibition of pathogen adhesion, direct antimicrobial and antibiofilm activity, selective prebiotic shaping of the gut microbiome, modulation of innate and adaptive immune responses, and reinforcement of mucosal barrier integrity in the gut and lungs. Breastfeeding constitutes a natural strategy for anti-infective protection in early childhood, while infant formulas supplemented with biotechnologically produced HMOs that are structurally identical to those in human milk provide measurable benefits for non-breastfed infants. Full article

Background/Objectives: The purpose of this proof-of-concept study was to examine the effects oligosaccharide 6′-sialyllactose (6′-SL) supplementation (900 mg/d) during training on exercise performance and training adaptations in recreationally active males. Methods: In a randomized, double-blind design, 19 healthy males (24.4 ± 6.0 yrs, 174.9 ± 5.9 cm, 82.0 ± 15.2 kg, 27.1 ± 4.7 kg/m², 26.4 ± 6.9% body fat) ingested 3 × 300 mg/d of a placebo or 6′-SL for 12 weeks while partaking in a supervised resistance-training program while following their normal diet. Body composition (DXA), body water, submaximal lactate and substrate oxidation, 5RM dynamic muscular strength, ventilatory anaerobic threshold (VANT), peak aerobic capacity (VO₂), blood lactate, cycling anaerobic sprint capacity, and fasting blood samples were obtained at week 0, 6, and 12 of training and supplementation. Data were analyzed using multivariate and univariate general linear models (GLM) with repeated measures, along with assessments of mean changes from baseline and corresponding 95% confidence intervals. Results: Both groups observed positive training adaptations with no significant differences observed between groups in body composition, 5RM dynamic strength, or anaerobic sprint capacity. Significant interaction effects were observed VANT (p = 0.032), VO₂ at VANT (p = 0.028), and submaximal glucose and fat oxidation (p = 0.034) while time to reach peak VO₂ (p = 0.083), absolute (p = 0.075) and relative (p = 0.057) peak VO₂ approached significance. At Week 6, changes in time to peak effort (196 s [−16, 409], p = 0.068), absolute (0.76 L/min [−0.005, 1.53], p = 0.051) and relative (10.9 mL/kg/min [0.52, 21.5], p = 0.045), and fat oxidation (20.5% [3.1, 37.9], p = 0.023) were significantly greater in the 6′-SL group while VANT (−9.2% [−18.3, −0.04], p = 0.049), VO₂ at VANT (−4.8% [−9.8, 0.2], p = 0.06) and submaximal glucose oxidation values (−20.5% [−37.9, −3.1], p = 0.024) were lower with 6′-SL. After 12 weeks of training, VANT (−9.7% [−17.7, −1.5], p = 0.023) and VO₂ at VANT (−6.4% [−11.8, −1.0], p = 0.024) values were significantly lower in the 6′-SL group. No significant differences were observed in resting, submaximal, or maximal exercise blood lactate while the ratios of LDL to HDL (−0.27 [−0.53, −0.01], p = 0.042) and total cholesterol to HDL (−0.32 [−0.60, −0.04], p = 0.028) decreased significantly from baseline after 6 weeks of training with 6′-SL. Conclusions: 6′-SL supplementation did not promote greater gains dynamic strength, fat free mass or changes in body composition. However, while there was some evidence that 6′-SL supplementation influenced training-induced changes in aerobic capacity during the first six weeks, fewer effects were observed after 12 weeks. Moreover, several differences only approached significance in this small proof-of-concept study, so results should be viewed as exploratory and hypothesis generating for additional research. Full article

Nutrition in the early years of life plays a fundamental role in newborn growth, immune maturation, metabolic regulation, endocrine signaling, and neurological development, specifically through its interaction with the developing gut microbiota. Breast milk is the biological gold standard for infant nutrition; however, when breastfeeding is not possible, the development of formulations supplemented with bioactive substances can improve functional outcomes in comparison to standard milk formula. This narrative review discusses current evidence on formulas enriched with prebiotics, probiotics, postbiotics, synbiotics, human milk oligosaccharides, and other bioactive molecules. The review focuses on gut microbiota modulation, gastrointestinal function, growth and nutritional adequacy, immune development, infection-related outcomes, safety and tolerability, endocrine signaling, intestinal stem-cell regulation, obesity-related metabolic pathways, and emerging gut–brain axis interactions. Overall, available data indicate that bioactive-supplemented formulas are generally safe, well tolerated, and able to support normal growth, including in selected infants with specific clinical conditions. The most consistent effects are observed in the gastrointestinal tract, where supplementation promotes a more bifidogenic microbial profile, improves stool characteristics, supports intestinal barrier function, and influences microbial metabolic activity. By contrast, evidence regarding systemic immune effects, endocrine modulation, obesity prevention, and neurodevelopmental outcomes remains promising but heterogeneous and is still largely derived from preliminary human studies and experimental models. Therefore, these formulas may be considered a useful option when breastfeeding is not feasible, provided that their use is clinically appropriate and evidence based. Further studies are needed to clarify their long-term functional and clinical implications. Full article

Congenital heart disease (CHD) is the most common congenital anomaly worldwide and is associated with substantial infant morbidity and mortality. This narrative review synthesizes evidence linking CHD to alterations in the gut microbiome across neonatal, perioperative, and chronic stages and highlights a gut–heart–immune framework in which microbial imbalance, intestinal barrier dysfunction, and systemic inflammation may interact to influence clinical outcomes. Early infancy represents a potential window for microbiome and immune development, shaped by delivery mode and feeding, with many breastfed infants developing a Bifidobacterium-dominant community supported by human milk oligosaccharides. In CHD, abnormal splanchnic perfusion and hypoxemia, together with intensive care and perioperative exposures (fasting, delayed enteral feeding, antibiotics, acid suppression), may predispose to dysbiosis and impaired barrier function. Cardiac surgery with cardiopulmonary bypass can act as a “second hit,” with evidence of increased gut permeability, endotoxemia, inflammatory activation, and biomarker signals of enterocyte injury and tight-junction disruption. Clinically, these mechanisms align with gut-sensitive outcomes including necrotizing enterocolitis (especially in ductal-dependent lesions), feeding intolerance, and postoperative infection-risk phenotypes. Interventions show mixed evidence: human milk exposure appears protective for NEC risk, synbiotics demonstrated outcome benefits in a randomized trial of cyanotic CHD infants, while probiotics may modify dysbiosis without consistently preventing intestinal injury and require careful safety frameworks. Key research gaps include the need for longitudinal stage-based cohorts, integration of microbiome profiling with barrier injury and perfusion markers, and standardized safety monitoring in intervention trials. Full article

Toxicological risk assessment of food ingredients has traditionally relied on identifying a no-observed-adverse-effect level (NOAEL) or benchmark dose (BMD), followed by the application of default uncertainty factors (UFs) to derive health-based guidance values (HBGVs) such as the acceptable daily intake (ADI). While effective for conventional food additives, this approach may be inappropriate for nutrients and intrinsic food components with established physiological functions. This paper critically explores these limitations using free glutamate as a central example, alongside additional cases relevant to infant nutrition, including vitamin C, iodine, and human milk oligosaccharides (HMOs). Data on free glutamate in human milk show that breastfed infants habitually ingest amounts far exceeding additive-based ADIs without adverse effects, underscoring the limitations of applying default uncertainty factors and classical toxicological paradigms to endogenous nutrients. Comparable considerations apply to protein hydrolysates and amino acid-based infant formulas evaluated by EFSA, where growth, tolerance, and compositional suitability are integral to safety assessment. Overall, nutrient safety evaluation requires an integrative, physiology-informed framework that incorporates realistic exposure, developmental stage, and metabolic competence. Breast milk provides a biologically relevant reference, supporting a proportionate and science-based application of toxicological principles in infant nutrition. Full article

This study focuses on Lacto-N-neotetraose (LNnT), a core component of human milk oligosaccharides. Although LNnT has been demonstrated to promote early intestinal development and maintain gut homeostasis, its protective mechanism against D-galactose-induced intestinal injury and associated cognitive impairment remains unclear. This investigation systematically examined the protective effects and underlying mechanisms of LNnT against D-gal-induced colonic damage and cognitive impairment in mice. The results demonstrated that LNnT not only significantly improved systemic physiological phenotypes and upregulated the expression of colonic tight junction proteins to repair the intestinal barrier, but also effectively enhanced learning and memory abilities in mice. Concurrently, LNnT reduced serum proinflammatory factor levels, elevated the anti-inflammatory factor IL-10, and alleviated oxidative stress. Furthermore, LNnT remodeled the gut microbiome structure by increasing microbial diversity, enhancing beneficial bacteria abundance, and promoting short-chain fatty acid production. Untargeted metabolomics analysis further revealed that LNnT corrected metabolic disturbances by regulating key sphingolipid molecules (ceramide, sphingosine, S1P) and the expression of related metabolic enzymes (ACER2, SphK2). In summary, this study suggests that LNnT mitigates intestinal injury and improves cognitive function, potentially through modulation of the gut microbiota–sphingolipid metabolism axis, although further causal validation is warranted. These findings provide a mechanistic foundation for future studies exploring its potential as a functional dietary ingredient. Full article

Human milk oligosaccharides (HMOs) exhibit substantial inter-individual and secretor-dependent variation, yet comprehensive quantitative data across diverse maternal phenotypes remain limited. In this study, we analyzed 578 human milk samples from four Asian populations using a dual mass spectrometry approach, combining quadrupole time-of-flight (Q-TOF) for structural profiling and triple quadrupole (QQQ) mass spectrometry for absolute quantitation of 15 major HMOs. Samples were classified into Secretor (76.7%) and Non-Secretor (23.3%) groups based on α-1,2-fucosylated HMO profiles. Secretor milk was enriched in α-1,2-fucosylated HMOs, whereas Non-Secretor milk showed markedly reduced levels of these structures. However, Non-Secretor retained substantial total fucosylated HMOs (65–76% of Secretor levels), accompanied by increased α-1,3/4-fucosylated structures, including up to 3.2-fold higher levels of 3-fucosyllactose (3-FL). Sensitive QQQ quantitation further revealed trace levels of α-1,2-fucosylated HMOs in Non-Secretor at concentrations 10–100-fold lower than in Secretor. Correlation analysis indicated an inverse relationship between α-1,2- and α-1,3-fucosylation patterns, consistent with redistribution of fucosylation pathways. These findings suggest that the Non-Secretor phenotype represents a distinct compositional state rather than a simple loss of α-1,2-fucosylation and provide a quantitative framework for phenotype-informed nutritional strategies. Full article

Cow’s milk allergy (CMA) remains one of the most common food allergies in infancy, requiring the avoidance of cow’s milk and its derivatives. Breast milk is the best source of nutrition for infants. For those infants with CMA whose mothers are unable to breastfeed or choose not to, extensively hydrolysed formulas (eHFs) are widely recommended as first-line milk substitutes, whereas hydrolysed rice formulas (HRFs) are increasingly recognised as a viable alternative. This concept paper provides a healthcare professional (HCP) perspective on HRF, drawing on expert consensus from two meetings convened in 2025. Discussions noted the long history of safe and effective HRF use in Europe, its nutritional adequacy, and the evolving international guidelines supporting HRF as an alternative first-line option. A key meeting outcome was the development of a practical decision tree to help UK clinicians decide when HRF should be the preferred choice. Key considerations for its use in non-breastfed infants include the following: parental/caregiver stress related to persistent symptoms; ongoing symptoms despite multiple interventions; cultural and lifestyle choices; religious dietary requirements; and specialists’ recommendations. Secondary considerations highlighted by HCPs include the following: proven reactions whilst infants are breast-milk-fed together with parental request for formula; faltering growth; multiple symptoms; taste acceptance (older infants); and parental preference based on experience. The role of functional components, such as prebiotics and human milk oligosaccharides (HMOs), was noted in regard to the emerging evidence of benefits to the microbiome and immune development. The experts emphasised the importance of engaging HCPs across all levels of CMA care and addressing challenges in translating current guidance into treatment practice. It was concluded that, overall, HRF represents a nutritionally complete, plant-based alternative that has been shown to be well tolerated (taste, symptoms) in clinical studies. It can be used to broaden therapeutic options for infants with CMA in the UK who are not exclusively fed breast milk. Full article

Early life represents a critical developmental programming window during which nutrition and microbial exposures shape long-term physiological function. Feeding mode is a major determinant of infant gut microbiota assembly and metabolic activity. This narrative review synthesizes current evidence comparing breastfeeding (BF) and formula feeding in relation to microbial composition, functional capacity, and immune programming during the preweaning and early postweaning periods. BF may support a relatively stable, bifidobacteria-dominated microbiota enriched in pathways involved in carbohydrate utilization, vitamin biosynthesis, and immune modulation. Human milk oligosaccharides, secretory IgA, lactoferrin, and milk-associated microbes collectively guide microbial succession, enhance barrier integrity, and support immune tolerance. In contrast, formula-fed infants typically exhibit greater microbial diversity, earlier transition toward adult-like profiles, and increased abundance of facultative anaerobes, alongside the enrichment of pathways related to bile acid and amino acid metabolism. Microbiota patterns in formula-fed infants are further influenced by formula composition, including protein load, lipid structure, and supplementation with prebiotics, probiotics, and human milk oligosaccharide analogues. Although advances in formula design have reduced compositional gaps, functional differences in microbial stability and immune programming persist. Recognizing early infancy as a sensitive programming window underscores the need for microbiome-informed nutritional strategies and longitudinal, multi-omics research to clarify causal mechanisms and optimize early-life interventions. Full article

Human breast milk evolves beyond simple nutrition to function as a complex signaling system that promotes neonatal development. This review analyzes the bioactive components, delineating how its specific constituents compensate for the physiological vulnerabilities of the neonate. Additionally, the distinct roles of colostral and mature milk are in fortifying the immature immune system and promoting gastrointestinal maturation. Focus is placed on the prevention of necrotizing enterocolitis, where milk oligosaccharides and microbiome function to maintain mucosal integrity and symbiosis, while preventing pathogens’ adhesion. Furthermore, how breastfeeding duration is linked to long-term metabolic and immunological programming is evaluated. MicroRNAs and bioactive lipids actively modulate gene expression and immune responses, thereby reducing the incidence of metabolic diseases and childhood malignancies. By integrating findings, this article underscores the irreplaceable role of breast milk in clinical dietetics and pediatric care. 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

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

Background/Objectives: Oral hygiene is crucial for maintaining overall health, as poor oral care can lead to various systemic diseases. Although xylitol is widely used to inhibit plaque formation, more effective agents are needed to control oral biofilms. Herein, we evaluated the inhibitory effects of sialyllactose (SL), a type of human milk oligosaccharide (HMO), and its partial structure N-acetylneuraminic acid (Neu5Ac) against Streptococcus biofilm. Methods: Under a CO₂ atmosphere, Streptococcus mutans and mixed Streptococcus species were each cultivated in vitro, and the inhibitory effects of HMOs [2′-fucosyllactose, 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL)] and Neu5Ac on biofilm formation were evaluated. Bacterial biofilm formation was quantified using the crystal violet assay. Biofilm architecture and viability were visualized using confocal laser-scanning microscopy (CLSM) with SYTO9/propidium iodide staining. Transcriptomic responses of S. mutans biofilms to the test compounds were analyzed by RNA-Seq. Statistical analysis was performed using one-way analysis of variance followed by Tukey’s test. Results: SLs and Neu5Ac at 100 mM significantly inhibited S. mutans biofilm formation, with stronger effects than those of xylitol. The inhibitory effects varied among HMOs, with 6′-SL being more effective than 3′-SL and Neu5Ac being most effective. These effects were consistent in assays targeting biofilms formed by other S. mutans strains and in a mixed biofilm comprising Streptococcus species. Gene expression analysis suggested that the inhibitory mechanism involves the physical inhibition of surface adhesion and stress-induced regulation of gene expression. Conclusions: This study provides insights into the physiological significance of HMOs in the oral cavities of humans. HMOs exhibited potential as functional foods to control oral biofilm formation and reduce the risk of oral and systemic diseases. Full article

Background/Objectives: HMOs are the third most abundant solid component after lactose and fats in human milk. This study aimed to examine the relationships between maternal diet and HMO composition and concentration in human milk among lactating women in Latvia. Methods: Pooled 24 h human milk samples, 72 h food diaries, and questionnaires on anthropometric and sociodemographic characteristics were collected from 68 exclusively breastfeeding women residing in Latvia. HMOs were analyzed by UHPLC/FLD, and dietary data were analyzed using the Estonian NutriData program. Results: The eight most abundant HMO structures were determined with total concentration ranging between 178.66 and 32,910.09 mg L⁻¹. 2′-FL was the most prevalent HMO in human milk (median concentration—3647 mg L⁻¹), followed by 3′-FL (1436.74 mg L⁻¹). Participants had an insufficient intake of vegetables, fruits, berries, milk and dairy products, and fish, leading to vitamin A, vitamin C, folate, and iodine intakes lower than recommended for lactating women. Limitation or exclusion of milk and dairy products from the diet was associated with a higher 2′-FL concentration in human milk (p = 0.037). Preference for “zero sugar” products was associated with a higher 3′-FL, 6′-GL, LNnT, 6′-SL, LNDFH II concentration in human milk (p < 0.050). Dietary supplement use (e.g., vitamin D, calcium) was also associated with differences in HMO composition and concentration in milk (p < 0.050). Conclusions: The findings highlight the importance of dietary habits and supplement use in shaping HMO profiles, though more human milk samples and dietary data need to be evaluated to draw further conclusions. Full article