Specific Human Milk Oligosaccharides Research Articles

Consumption of different combinations of human milk oligosaccharides in the first 6 mo of infancy is positively associated with early cognition at 2 y of age in a longitudinal cohort of Latino children

BackgroundLactation has been widely associated with optimal neurocognitive development, but the underlying mechanism remains unknown. Human milk oligosaccharides (HMOs) are complex sugars that support brain development, but previous studies examining their associations with cognition have yielded inconsistent findings. ObjectivesThis study aimed to provide a broader understanding of how HMOs jointly influence cognition. MethodsWe used data from an ongoing longitudinal cohort of Latino mother–infant dyads. Human milk samples from 1 mo (n = 157) and 6 mo (n = 107) postpartum were assessed for the 19 most abundant HMOs. Cognitive performance was assessed at 2 y using the Bayley Scale of Infant and Toddler Development. A partial least squares model identified HMO combinations predictive of cognitive scores. ResultsAt 1 mo, the combination of higher concentrations of lacto-N-neotetraose (LNnT), lacto-N-tetraose (LNT), lacto-N-fucopentaose (LNFP)-III, 6′-sialyllactose, and 2′-fucosyllactose (FL) with lower concentrations of sialyllacto-N-tetraose (LST) b, LNFP-II, fucodisialyllacto-N-hexaose, and 3-FL significantly predicted higher cognitive scores (β: 0.61; 95% confidence interval [CI]: 0.30, 0.92), explaining an additional 8% of the variance over a model with only nuisance covariates (11%). Additional analyses revealed that the combination of higher LNFP-III and lower LSTb alone explained 5% more of the variation in cognitive scores (β: 0.66; 95% CI: 0.24, 1.09). At 6 mo (n = 107), higher LNnT, LNT, and LNFP-III and lower 3FL and LSTb concentrations explained an extra 6% of the variance in cognitive scores (β: 0.43; 95% CI: 0.12, 0.75). ConclusionsThis study highlights specific HMO combinations in early life influencing cognitive performance at 2 y.

Exploring the impact of maternal factors and dietary habits on human milk oligosaccharide composition in early breastfeeding among Mexican women

Human milk oligosaccharides (HMOs) promote adequate intestinal microbiota development and favor the immune system's maturation and cognitive development. In addition to non-modifiable factors, HMOs composition can be influenced by other factors like body mass index and eating habits, but the reports are discrepant. The aim of this work was to describe the correlation between maternal factors and HMOs concentration in colostrum in 70 women from northeastern Mexico categorized into women with normal weight and women with overweight or obesity. The absolute concentration of six HMOs were significantly lower in women with overweight or obesity compared to women with normal weight (LNFPI p = 0.0021, 2’-FL p = 0.0304, LNT p = 0.0492, LNnT p = 0.00026, 3’-SL p = 0.0476, 6’-SL p = 0.00041). Another main finding was that the frequency of consumption of food groups such as vegetables, fruits and meats was positively correlated to specific HMOs (Poblano chili and 2’-FL; rs = 0.702, p = 0.0012; Orange or tangerine and 3-FL; rs = 0.428, p = 0.0022; Chicken and 2'-FL; rs = 0.615, p = 0.0039). This study contributes to the elucidation of how maternal factors influence the composition of HMOs and opens possibilities for future research aimed at mitigating overweight or obesity, consequently improving the quality of human milk.

Engineered plants provide a photosynthetic platform for the production of diverse human milk oligosaccharides

Human milk oligosaccharides (HMOs) are a diverse class of carbohydrates which support the health and development of infants. The vast health benefits of HMOs have made them a commercial target for microbial production; however, producing the approximately 200 structurally diverse HMOs at scale has proved difficult. Here we produce a diversity of HMOs by leveraging the robust carbohydrate anabolism of plants. This diversity includes high-value and complex HMOs, such as lacto-N-fucopentaose I. HMOs produced in transgenic plants provided strong bifidogenic properties, indicating their ability to serve as a prebiotic supplement with potential applications in adult and infant health. Technoeconomic analyses demonstrate that producing HMOs in plants provides a path to the large-scale production of specific HMOs at lower prices than microbial production platforms. Our work demonstrates the promise in leveraging plants for the low-cost and sustainable production of HMOs.

In vitro Digestion: Exploring the probiotic abilities and metabolization of human milk oligosaccharides by two strains of Limosilactobacillus fermentum isolated from breast milk

Human breast milk (HBM) serves as the most optimal nourishment for infants, not only providing essential nutrition but also boasting a rich array of immune components. These include secretory antibodies, immune cells, antimicrobial proteins (like lactoferrin and lysozyme), cytokines, and human milk oligosaccharides. Today, the presence of a specific microbiome in human milk is known. Our primary research involves the examination of certain probiotic properties displayed by two strains of Limosilactobacillus fermentum, which were isolated from breast milk. Furthermore, our goal was to evaluate their ability to metabolize breast milk-derived oligosaccharides through an in vitro digestion simulation system. The in vitro model simulating gastrointestinal digestion was performed according to INFOGEST method with some modification. We used various molecular techniques to isolate and identify strains from breast milk. Additionally, we employed different biochemical analyses to determine specific enzyme activities, and we also assessed the fundamental probiotic characteristics of two strains Limosilactobacillus fermentum. We found good probiotic characteristics in the examined strains, as well as favorable growth properties in the presence of specific human milk oligosaccharides. In this regard, we believe that breast milk represents a rich source for isolating potential probiotic strains.

Longitudinal quantification of Bifidobacterium longum subsp. infantis reveals late colonization in the infant gut independent of maternal milk HMO composition

Breast milk contains human milk oligosaccharides (HMOs) that cannot be digested by infants, yet nourish their developing gut microbiome. While Bifidobacterium are the best-known utilizers of individual HMOs, a longitudinal study examining the evolving microbial community at high-resolution coupled with mothers’ milk HMO composition is lacking. Here, we developed a high-throughput method to quantify Bifidobacterium longum subsp. infantis (BL. infantis), a proficient HMO-utilizer, and applied it to a longitudinal cohort consisting of 21 mother-infant dyads. We observed substantial changes in the infant gut microbiome over the course of several months, while the HMO composition in mothers’ milk remained relatively stable. Although Bifidobacterium species significantly influenced sample variation, no specific HMOs correlated with Bifidobacterium species abundance. Surprisingly, we found that BL. infantis colonization began late in the breastfeeding period both in our cohort and in other geographic locations, highlighting the importance of focusing on BL. infantis dynamics in the infant gut.

The Role of Human Milk Oligosaccharides in Myelination, Socio-Emotional and Language Development: Observational Data from Breast-Fed Infants in the United States of America.

Infancy is a critical period for neurodevelopment, which includes myelination, synaptogenesis, synaptic pruning, and the development of motor, social-emotional, and cognitive functions. Human milk provides essential nutrients to the infant's developing brain, especially during the first postnatal months. Human milk oligosaccharides (HMOs) are a major component of human milk, and there is growing evidence of the association of individual HMOs with cognitive development in early life. However, to our knowledge, no study has explained these associations with a mechanism of action. Here, we investigated possible mediating associations between HMOs in human milk, brain myelination (measured via myelin water fraction), and measures of motor, language (collected via the Bayley Scales of Infant and Toddler Development (Bayley-III)), and socioemotional development (collected via the Ages and Stages Questionnaire: Social-Emotional Version (ASQ-SE)) in healthy term-born breast-fed infants. The results revealed an association between 6'Sialyllactose and social skills that was mediated by myelination. Furthermore, associations of fucosylated HMOs with language outcomes were observed that were not mediated by myelination. These observations indicate the roles of specific HMOs in neurodevelopment and associated functional outcomes, such as social-emotional function and language development.

Alterations of milk oligosaccharides in mothers with gestational diabetes mellitus impede colonization of beneficial bacteria and development of RORγt+ Treg cell-mediated immune tolerance in neonates

ABSTRACT Gestational diabetes mellitus (GDM) is an increasing public health concern that significantly increases the risk of early childhood allergic diseases. Altered maternal milk glycobiome may strongly affect gut microbiota and enteric-specific Treg cell-mediated development of immune tolerance in GDM infants. In this study, we found that, compared with healthy Chinese mothers, mothers with GDM had significantly lower levels of total and specific human milk oligosaccharides (HMOs) in their colostrum that subsequently increased with extension of lactation. This alteration in HMO profiles significantly delayed colonization of Lactobacillus and Bifidobacterium spp. in their breast-fed infants, resulting in a distinct gut microbial structure and metabolome. Further experiments in GDM mouse models indicated that decreased contents of milk oligosaccharides, mainly 3ʹ-sialyllactose (3ʹ-SL), in GDM maternal mice reduced colonization of bacteria, such as L. reuteri and L. johnsonii, in the neonatal gut, which impeded development of RORγt+ regulatory T (Treg) cell-mediated immune tolerance. Treatment of GDM neonates with 3ʹ-SL, Lactobacillus reuteri (L. reuteri) and L. johnsonii promoted the proliferation of enteric Treg cells and expression of transcription factor RORγt, which may have contributed to compromising ovalbumin (OVA)-induced allergic responses. In vitro experiments showed that 3ʹ-SL, metabolites of L. johnsonii, and lysates of L. reuteri stimulated differentiation of mouse RORγt+ Treg cells through multiple regulatory effects on Toll-like receptor, MAPK, p53, and NOD-like receptor signaling pathways. This study provides new ideas for the development of gut microbiota and immune tolerance in GDM newborns.

Role of human milk oligosaccharide metabolizing bacteria in the development of atopic dermatitis/eczema.

Despite affecting up to 20% of infants in the United States, there is no cure for atopic dermatitis (AD), also known as eczema. Atopy usually manifests during the first six months of an infant's life and is one predictor of later allergic health problems. A diet of human milk may offer protection against developing atopic dermatitis. One milk component, human milk oligosaccharides (HMOs), plays an important role as a prebiotic in establishing the infant gut microbiome and has immunomodulatory effects on the infant immune system. The purpose of this review is to summarize the available information about bacterial members of the intestinal microbiota capable of metabolizing HMOs, the bacterial genes or metabolic products present in the intestinal tract during early life, and the relationship of these genes and metabolic products to the development of AD/eczema in infants. We find that specific HMO metabolism gene sets and the metabolites produced by HMO metabolizing bacteria may enable the protective role of human milk against the development of atopy because of interactions with the immune system. We also identify areas for additional research to further elucidate the relationship between the human milk metabolizing bacteria and atopy. Detailed metagenomic studies of the infant gut microbiota and its associated metabolomes are essential for characterizing the potential impact of human milk-feeding on the development of atopic dermatitis.

Early development of infant gut microbiota in relation to breastfeeding and human milk oligosaccharides.

Infant gut microbiota composition is influenced by various factors early in life. Here, we investigate associations between infant gut microbiome development, infant age, breastfeeding duration, and human milk oligosaccharides (HMO) composition in breastmilk. A total of 94 mother-infant pairs were recruited as part of the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF) (Cambridge, UK). Infant stool samples (n = 337) were collected at 2 week, 6 week, 3 month, and 6 month of age. The 16S rRNA V3-V4 rRNA region was sequenced using MiSeq Illumina to determine microbiota composition and diversity. Mother's hindmilk samples were collected at birth, 2 week, 6 week, 3 month, and 6 month postpartum. Concentrations of five neutral [2'FL, 3'FL, lacto-N-fucopentaose 1 (LNFP1), LNnT, LNT] and two acidic (3'SL, and 6'SL) HMOs were measured in all milk samples using High-Performance Anion-Exchange Chromatography with Pulsed Amperometric Detection (HPAEC-PAD). We explored the associations between infant gut microbiome parameters and age, duration of exclusive breastfeeding (EBF), and levels of individual HMOs. Bifidobacterium was the most abundant genus in infant stool at all-time points, irrespective of breastfeeding duration, with an overall mean relative abundance of 70%. The relative abundance of B. bifidum in stool from infants who were breastfed for longer than 6 months was significantly higher compared to the infant breastfed up to 3 months (p = 0.0285). Alpha-diversity (both Shannon and ASV-level Richness) of infant gut microbiota showed a biphasic change with infant age, decreasing from 2 weeks until 3 months and then increasing until 6 months of age. Bifidobacterium relative abundance was associated with higher concentrations of 2'FL and LNFP1 in breastmilk across all time-points (p = 0.049 and 0.017, respectively), with trends toward a higher abundance of B. longum species. No significant association with Bifidobacterium was found for breastmilk LNnT, 3'SL, and 6'SL levels. Our study is in line with previous data demonstrating that EBF duration in the first months of life impacts infant gut microbiota composition. The observed links between specific HMOs in breastmilk and bacteria in infant stool provide evidence of how mother's milk affects infant microbiome development.

Specific Human Milk Oligosaccharides Differentially Promote Th1 and Regulatory Responses in a CpG-Activated Epithelial/Immune Cell Coculture.

Proper early life immune development creates a basis for a healthy and resilient immune system, which balances immune tolerance and activation. Deviations in neonatal immune maturation can have life-long effects, such as development of allergic diseases. Evidence suggests that human milk oligosaccharides (HMOS) possess immunomodulatory properties essential for neonatal immune maturation. To understand the immunomodulatory properties of enzymatic or bacterial produced HMOS, the effects of five HMOS (2'FL, 3FL, 3'SL, 6'SL and LNnT), present in human milk have been studied. A PBMC immune model, the IEC barrier model and IEC/PBMC transwell coculture models were used, representing critical steps in mucosal immune development. HMOS were applied to IEC cocultured with activated PBMC. In the presence of CpG, 2'FL and 3FL enhanced IFNγ (p < 0.01), IL10 (p < 0.0001) and galectin-9 (p < 0.001) secretion when added to IEC; 2'FL and 3FL decreased Th2 cell development while 3FL enhanced Treg polarization (p < 0.05). IEC were required for this 3FL mediated Treg polarization, which was not explained by epithelial-derived galectin-9, TGFβ nor retinoic acid secretion. The most pronounced immunomodulatory effects, linking to enhanced type 1 and regulatory mediator secretion, were observed for 2'FL and 3FL. Future studies are needed to further understand the complex interplay between HMO and early life mucosal immune development.

Can Human Milk Oligosaccharides Modulate the Allergic Response and Improve the Management of Cow’s Milk Protein Allergy?

During this symposium, leading experts in paediatric allergy and immunology reviewed new evidence for the role of human milk oligosaccharides (HMO) in supporting the development of the infant microbiota and modulating the immune system, thereby improving the clinical management of cow’s milk protein allergy (CMPA). Liam O’Mahony, University College Cork, Ireland, explored the mechanisms by which HMOs can modify the gut microbiome and beneficially influence allergic and infectious responses in both healthy infants and those with CMPA. New data from the CINNAMON study were showcased by Claire Boulangé, Nestlé Institute of Health Sciences, Lausanne, Switzerland, highlighting key mechanisms by which specific HMOs can support the microbiome and modulate metabolome production that may lead to important immune benefits in CMPA. Finally, Anna Nowak-Węgrzyn, Professor of Pediatrics and Chief of the Division of Pediatric Allergy and Immunology at the Grossman School of Medicine, New York University (NYU) Langone Health, USA, presented results from the Platypus study, in which infants with moderate-to-severe CMPA were fed an amino acid (AA)-based formula containing two HMOs. Symptoms of CMPA decreased significantly in infants fed the HMO-supplemented formula, and these clinical improvements were accompanied by normal growth and positive changes to the faecal microbiome. Collectively, these findings translate to important immune benefits and a key role for HMO-supplemented formula in the clinical management of CMPA.

Biology of human milk oligosaccharides: From basic science to clinical evidence.

Human milk oligosaccharides (HMOs) have been researched by scientists for over 100 years, driven by the substantial evidence for the nutritional and health benefits of mother's milk. Yet research has truly bloomed during the last decade, thanks to progress in biotechnology, which has allowed the production of large amounts of bona fide HMOs. The availability of HMOs has been particularly crucial for the renewed interest in HMO research because of the low abundance or even absence of HMOs in farmed animal milk. This interest is reflected in the increasing number of original research publications and reviews on HMOs. Here, we provide an overview and critical discussion on structure–function relations of HMOs that highlight why they are such interesting and important components of human milk. Clinical observations in breastfed infants backed by basic research from animal models provide guidance as to what physiological roles for HMOs are to be expected. From an evidence‐based nutrition viewpoint, we discuss the current data supporting the clinical relevance of specific HMOs based on randomised placebo‐controlled clinical intervention trials in formula‐fed infants.

Human milk oligosaccharide profiles and child atopic dermatitis up to 2years of age: The Ulm SPATZ Health Study.

Human milk oligosaccharides (HMOs) have several biological functions. Yet, very few studies have investigated the effect of HMOs on the development of allergies and even fewer on their specific associations with atopic dermatitis (AD) during early childhood. This study investigated whether individual HMO concentrations, measured at two time points of lactation, were associated with reported diagnosis of AD in children up to twoyears of age. Outcome data were available for HMOs measured in human milk samples collected at 6weeks (n=534) and 6months (n=356) of lactation. Associations of HMOs with AD, ascertained from parents and pediatricians at ages one and two years, were assessed in crude and adjusted logistic regression models. Few associations were statistically significant at the conventional level (p<.05), for example, 6-week Lacto-N-neotetraose with 2-year AD [OR 95%CI: 0.82 (0.66, 1.00)] and 6-month 3'-sialyllactose among non-secretor mothers with 1-year AD [2.59 (1.53, 6.81)]. Importantly, accounting for multiple testing, these and all further associations were not statistically significant (all p>.0031, which is the threshold for statistical significance after correction for multiple testing). Our findings suggest that the intake of different levels (or even absence) of the individual HMOs measured at 6weeks and 6months of lactation, in the current study, is not significantly associated with the development of AD in early childhood. Given the exploratory nature of our study and the limited sample size, these results should be interpreted with caution. The specific HMOs for which we show plausible associations at conventional level may warrant further research and investigation.

Galactooligosaccharides and 2′-fucosyllactose can directly suppress growth of specific pathogenic microbes and affect phagocytosis of neutrophils

ObjectivesNon-digestible oligosaccharides such as milk oligosaccharides (MOS) can regulate and influence immune function. As an example, galactooligosaccharides (GOS), and 2′-fucosyllactose (2′-FL; a specific human MOS) regulate immune development and functionality. Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA), both serious pathogens, can cause severe and life-threatening infections. The aim of this study was to examine the effects of GOS and 2′-FL on bacterial growth and on polymorphonuclear (PMN) phagocytosis. MethodsPMNs were isolated from heparinized whole human blood before treatment/incubation with GOS (0.0625–10%), 2′-FL (0.5–2.5%) and/or GOS combined with 2′-FL (GOS 10%/2′-FL 2.5%; GOS 0.0625%/2′-FL 0.5%) and incubation with green florescent protein (GFP)-labeled SA or PA for 60 h. GFP-relative fluorescent units (GFP-RFU) was measured ≤60 h using a plate reader. Bacterial lag time was determined by the time to onset of exponential bacterial fluorescence/growth alone or after co-culture of bacteria and PMN. Viable bacterial colony-forming units (CFUs) were determined after 60 h. ResultsSA and PA growth lag time was suppressed by co-incubation with GOS in a concentration-dependent manner. This was significant for both SA and PA at concentrations >2.5% GOS (P ≤ 0.05 for both SA and PA) but only for SA at 1% GOS (P ≤ 0.05). 1.5% 2′-FL significantly suppressed the lag time of SA growth (P ≤ 0.05) and was effective against SA and PA at 2.5% (P ≤ 0.01 and P ≤ 0.01, respectively). GOS (10%, 5%) and 2.5% 2′-FL significantly decreased SA and PA bacterial growth/CFUs (P ≤ 0.05). ConclusionThe data suggests that both GOS and 2′-FL can suppress growth of serious pathogens and enhance phagocytosis.

Selected Human Milk Oligosaccharides Added to Infant Formulas for Term Infants.

The benefits of breastfeeding, such as reduced risk of gastrointestinal and respiratory tract infections, depend largely on the presence of bioactive compounds in breast milk, including human milk oligosaccharides (HMOs). The presence of HMOs represents one of the largest differences in composition between breast milk and infant formula. Currently, progress in biotechnology allows the production of selected HMOs such as 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT), which are increasingly being added to infant formulas to narrow the difference between breast milk and formula. It is important to differentiate HMOs naturally occurring in human breast milk from those biotechnologically produced, which, while identical to HMOs in breast milk, do not originate from breast milk. This chapter summarizes basic facts about HMOs, findings from observational studies assessing the relationship between specific HMOs and clinical effects, and evidence from randomized controlled trials with structures identical to HMOs in breast milk added to infant formulas. Overall, the findings from some recently published trials provide reassurance that infant formulas supplemented with selected structures identical to HMOs, specifically 2'-FL with/out LNnT, are safe and well tolerated, and may have favorable effects on some health outcomes and medication usage. Further studies are needed.

Associations of Human Milk Oligosaccharides With Otitis Media and Lower and Upper Respiratory Tract Infections up to 2 Years: The Ulm SPATZ Health Study.

Background: Human milk oligosaccharides (HMOs) support and concurrently shape the neonatal immune system through various mechanisms. Thereby, they may contribute to lower incidence of infections in infants. However, there is limited evidence on the role of individual HMOs in the risk of otitis media (OM), as well as lower and upper respiratory tract infections (LRTI and URTI, respectively) in children up to 2 years.Objective: To investigate whether individual HMO concentrations measured at 6 weeks of lactation were associated with risk of OM, LRTI or URTI up to 2 years in breastfed infants. Associations with OM, LRTI and URTI were determined for the most prominent human milk oligosaccharides including 13 neutral, partly isomeric structures (trioses up to hexaoses), two acidic trioses, and lactose.Design: HMO measurements and physician reported data on infections were available from human milk samples collected at 6 weeks postpartum (n = 667). Associations of HMOs with infections were assessed in crude and adjusted models using modified Poisson regression.Results: Absolute concentrations (median [min, max], in g/L) of 2′-fucosyllactose (2′-FL) tended (p = 0.04) to be lower, while lacto-N-tetraose (LNT) was higher in the milk for infants with OM in the 1st year of life (p = 0.0046). In the milk of secretor mothers, LNT was significantly higher in the milk for infants with OM (RR [95% CI]: 0.98 [0.15, 2.60]) compared to infants without OM (RR [95% CI]: 0.76 [0.14, 2.90]) at 1 year (p = 0.0019). No statistically significant milk group differences and associations were observed for OM, LRTI, and URTI (p > 0.0031).Conclusion: Our findings suggest that neither prominent neutral individual HMOs (ranging from 2′-FL to LNDFHs) nor acidic human milk sialyllactoses or lactose are significantly associated with a reduced or increased risk of infections in infants up to 2 years of age. Further research is needed to determine whether specific HMOs could potentially reduce the incidence or alleviate the course of distinct infections in early life.

Human milk oligosaccharides alleviate stress-induced visceral hypersensitivity and associated microbiota dysbiosis

Pain-related functional gastrointestinal disorders (FGIDs) are characterized by visceral hypersensitivity (VHS) associated with alterations in the microbiota-gut-brain axis. Since human milk oligosaccharides (HMOs) modulate microbiota, gut and brain, we investigated whether HMOs impact VHS, and explored the role of gut microbiota. To induce VHS, C57BL/6JRj mice received hourly water avoidance stress (WAS) sessions for 10 d, or antibiotics (ATB) for 12 d. Challenged and unchallenged (Sham) animals were fed AIN93M diet (Cont) or AIN93M containing 1% of a 6-HMO mix (HMO6). VHS was assessed by monitoring the visceromotor response to colorectal distension. Fecal microbiome was analyzed by shotgun metagenomics. The effect of HMO6 sub-blends on VHS and nociceptive pathways was further tested using the WAS model. In mice fed Cont, WAS and ATB increased the visceromotor response to distension. HMO6 decreased WAS-mediated electromyographic rise at most distension volumes and overall Area Under Curve (AUC=6.12±0.50 in WAS/HMO6 vs. 9.46±0.50 in WAS/Cont; P<.0001). In contrast, VHS in ATB animals was not improved by HMO6. In WAS, HMO6 promoted most microbiota taxa and several functional pathways associated with low VHS and decreased those associated with high VHS. Among the sub-blends, 2’FL+DFL and LNT+6’SL reduced visceromotor response close to Sham/Cont values and modulated serotoninergic and CGRPα-related pathways. This research further substantiates the capacity of HMOs to modulate the microbiota-gut-brain communication and identifies mitigation of abdominal pain as a new HMO benefit. Ultimately, our findings suggest the value of specific HMO blends to alleviate pain associated FGIDs such as infantile colic or Irritable Bowel Syndrome.

The human milk oligosaccharide 3’sialyllactose promotes inflammation resolution and reduces atherosclerosis development.

Background and Aims: Macrophages contribute to the induction and resolution of inflammation and play a central role in the chronic low-grade inflammation in cardiovascular diseases caused by atherosclerosis. Human milk oligosaccharides (HMOs) are complex unconjugated glycans unique to human milk that benefit infant health and act as innate immune modulators. In this study, we tested the hypothesis that a specific HMO attenuates atherosclerosis low-grade macrophage inflammation and atherosclerosis development in mice.

Tailoring Human Milk Oligosaccharides to Prevent Necrotising Enterocolitis Among Preterm Infants.

Necrotising enterocolitis (NEC) is a devastating disease affecting preterm infants, with little improvement in mortality rates and treatment strategies in the last 30 years. Human milk oligosaccharides (HMOs) are emerging as a potential preventive therapy, with multiple protective functions postulated. Our aim is to summarise the evidence concerning the role of HMOs in NEC development and emerging strategies to tailor the delivery of HMOs to preterm infants. Most research efforts to date have focused on supplementing preterm infants with simple oligosaccharides, which are structurally different to HMOs and derived mainly from plants. Clinical trials demonstrate limited benefits for NEC prevention arising from the use of these supplements. Alternative strategies under investigation include optimising HMOs for infants receiving donor human milk, concentrating oligosaccharides from donor human milk and from animal milks, as well as more sophisticated synthetic oligosaccharide production strategies. Critically, high quality evidence to support implementation of any of these approaches in the neonatal unit is lacking. Whether it is a specific HMO alone or a combination of HMOs that exert protective effects remains to be elucidated. Further challenges include how best to manufacture and administer oligosaccharides whilst retaining bioactivity and safety, including evaluation of the long-term effects of altering the balance of HMOs and gut microbiota in preterm infants. While several human clinical trials are underway, further research is needed to understand whether a tailored approach to oligosaccharide supplementation is beneficial for preterm infants.

Blends of Human Milk Oligosaccharides Confer Intestinal Epithelial Barrier Protection In Vitro

Breastfeeding is integral in the proper maturation of the intestinal barrier and protection against inflammatory diseases. When human milk (HM) is not available, supplementation with HM bioactives like Human Milk Oligosaccharides (HMOs) may help in providing breastfeeding barrier-protective benefits. An increasing HMO variety is becoming industrially available, enabling approaching the HMO complexity in HM. We aimed at assessing the impact of blends of available HMOs on epithelial barrier function in vitro. The capacity of individual [2′-Fucosyllactose (2′FL), Difucosyllactose, Lacto-N-tetraose, Lacto-N-neotetraose, 3′-Siallylactose and 6′-Siallylactose] or varying combinations of 3, 5 and 6 HMOs to modulate fluorescein-isothiocyanate (FITC)-labelled Dextran 4 KDa (FD4) translocation and/or transepithelial resistance (TEER) was characterized in Caco-2: HT29- methotrexate (MTX) cell line monolayers before and after an inflammatory challenge with TNF-α and IFN-γ. The six HMO blend (HMO6) dose-dependently limited the cytokine-induced FD4 translocation and TEER decrease and increased TEER values before challenge. Similarly, 3 and 5 HMO blends conferred a significant protection against the challenge, with 2′FL, one of the most abundant but most variable oligosaccharides in HM, being a key contributor. Overall, our results suggest differential ability of specific HMOs in modulating the intestinal barrier and support the potential of supplementation with combinations of available HMOs to promote gut health and protect against intestinal inflammatory disorders.