Search Results (38)

Background/Objectives: Early childhood is a critical window of development, which is influenced by early life exposures including breastfeeding. Observational and preclinical studies have linked human milk oligosaccharides (HMOs) with neurocognitive development. However, less attention has focused on behavioral outcomes including temperament and eating behaviors. Herein, we investigated the associations between HMO consumption and child temperament and child eating behaviors through four years of age. Methods: Participants were drawn from the STRONG Kids 2 cohort. Human milk was collected at 6 weeks postpartum, and HMO relative abundances were determined by HPLC-MS. Using validated questionnaires, child temperament was assessed at 3, 18, and 48 months of age, and child eating behaviors were measured at 12, 18, 24, 36, and 48 months of age. After adjusting for covariates, multiple linear regressions were carried out to assess the relationship between HMOs and the outcome measures. Results: The HMO profile of mothers showed two distinct clusters explained by maternal secretor status. Significant associations between HMO and surgency were only found in the full cohort and secretors, while more associations between HMO and negative affectivity were observed in non-secretors. A significant number of associations was observed between HMOs and child eating behaviors in full cohort, secretors, and non-secretors. HMO diversity, total fucosylation, and total sialylation were positively associated with food responsiveness, while neutral HMOs presented negative associations. However, these associations with food responsiveness were not observed in non-secretors. Conclusions: HMO profiles were associated with behavioral outcomes in the children, with variations by child age and maternal secretor status, highlighting the potential role of HMOs within the broader context of maternal and postnatal influences. Full article

Enteric pathogens remain a health threat for children in low-income countries. A single nucleotide polymorphism (SNP) in the FUT2 gene that precludes the expression of fucosyltransferase 2 has been reported to influence the susceptibility to rotavirus and norovirus infections. The aim of this study was to investigate the association between G428A at rs601338 (stop codon variant) in the FUT2 gene and a range of enteric pathogens in children under 5 years of age. Rectal swab samples from 668 children (median age 13.6 months, 51% males, 93% rotavirus vaccinated, 468 with diarrhea) from Rwanda were analyzed via PCR for pathogen detection and SNP genotyping. A FUT2 stop codon (‘non-secretor’ status) was found in 19% of all children. Rotavirus was detected in 5.3% of non-secretors compared with in 13% of secretors (OR = 0.39, p = 0.019). Rotavirus P[8] was the predominant genotype and was found in 2.3% of non-secretors compared with 8.8% of secretors (p = 0.009). There was no association with any other pathogen, including noroviruses, of which 2 of 14 GII.4 infections were detected among non-secretors. Thus, the FUT2 stop codon variant was associated with rotavirus but not with any other pathogen. Full article

Background: Human milk oligosaccharides (HMOs) serve as critical bioactive components supporting infant growth and development. However, the influence of maternal metabolic factors during lactation on HMOs remains to be fully elucidated. This study aimed to investigate the association between maternal metabolic factors and HMOs, as well as the potential mediating effects of these factors. Methods: An observational cross-sectional study was conducted in Central South China, enrolling 196 lactating mothers. HMOs were quantified using liquid chromatography-tandem mass spectrometry. Maternal metabolic factors were assessed through physical examinations. Associations between metabolic factors and HMOs were analyzed using linear regression, and mediation effects were evaluated. Results: HMOs from Central South China were predominantly composed of neutral fucosylated HMOs. Significant differences were observed in the levels of several HMOs across maternal age groups and lactation periods. The concentration of 3′-sialyllactose (3′-SL) exhibited a negative association with the pre-pregnancy body mass index (BMI) (β = −0.16, 95% CI: −0.29, −0.03; p = 0.02), while a positive association was found with maternal heart rate (β = 0.14, 95% CI: 0.01, 0.27; p = 0.04). However, these associations were different between secretor and non-secretor mothers. Associations of 3′-SL with pre-pregnancy BMI and maternal HR were only found in the secretor mothers. Triglycerides and low-density lipoprotein cholesterol mediated the associations between maternal pre-pregnancy BMI and 3′-sialyllactose (3′-SL). Conclusions: The variations of several HMOs among mothers from Central South China were associated with maternal age and lactation period. The concentration of 3′-SL was negatively correlated with maternal pre-pregnancy BMI. The potential mechanism underlying the influence of maternal BMI on 3′-SL levels may involve maternal lipid metabolism and genetic factors. Full article

Human milk oligosaccharides (HMOs), the third most abundant solid component in human milk, vary significantly among women due to factors such as secretor status, race, geography, season, maternal nutrition and weight, gestational age, and delivery method. In recent studies, HMOs have been shown to have a variety of functional roles in the development of infants. Because HMOs are not digested by infants, they act as metabolic substrates for certain bacteria, helping to establish the infant’s gut microbiota. By encouraging the growth of advantageous intestinal bacteria, these sugars function as prebiotics and produce short-chain fatty acids (SCFAs), which are essential for gut health. HMOs can also specifically reduce harmful microbes and viruses binding to the gut epithelium, preventing illness. HMO addition to infant formula is safe and promotes healthy development, infection prevention, and microbiota. Current infant formulas frequently contain oligosaccharides (OSs) that differ structurally from those found in human milk, making it unlikely that they would reproduce the unique effects of HMOs. However, there is a growing trend in producing OSs resembling HMOs, but limited data make it unclear whether HMOs offer additional therapeutic benefits compared to non-human OSs. Better knowledge of how the human mammary gland synthesizes HMOs could direct the development of technologies that yield a broad variety of complex HMOs with OS compositions that closely mimic human milk. This review explores HMOs’ complex nature and vital role in infant health, examining maternal variation in HMO composition and its contributing factors. It highlights recent technological advances enabling large-scale studies on HMO composition and its effects on infant health. Furthermore, HMOs’ multifunctional roles in biological processes such as infection prevention, brain development, and gut microbiota and immune response regulation are investigated. The structural distinctions between HMOs and other mammalian OSs in infant formulas are discussed, with a focus on the trend toward producing more precise replicas of HMOs found in human milk. Full article

Interferons (IFNs) produced by airway epithelial cells are crucial in defending against pathogens. Fluctuations in IFN-λ levels may influence coronavirus disease 19 (COVID-19) severity. However, conflicting data have been reported regarding serum IFN-λ concentrations in COVID-19 patients. To address this, we evaluated serum IFN-λ levels over time in moderate and severe COVID-19 patients and their association with cytokine production and clinical parameters using the enzyme-linked immunosorbent assay (ELISA) and the Bio-Plex Pro Human Cytokine 17-plex Assay. Results from testing 51 COVID-19 patients showed that 68% lacked detectable serum IFN-λ. Among non-IFN-λ secretors, severe COVID-19 predominated. In contrast, IFN-λ secretors displayed stable IFN-λ levels in moderate cases, while severe cases showed a decline over time, which persisted even after recovery. A negative correlation was observed between IFN-λ levels and inflammatory markers. This, combined with an increase in tumor necrosis factor alpha (TNF-α) and clinical improvement, suggests a regulatory role for IFN-λ in promoting faster recovery. Despite this, survival rates were similar between the groups, indicating that while IFN-λ influences the course of the disease, it does not directly affect overall survival. In conclusion, IFN-λ is vital, but not unique, for the antiviral response and COVID-19 recovery. Simultaneously, serum IFN-λ deficiency signifies severe COVID-19. Full article

Human milk, the gold standard in infant nutrition, is a unique fluid that provides essential nutrients such as lactose, lipids, proteins, and free oligosaccharides. While its primary role is nutritional, it also protects against pathogens. This protection mainly comes from immunoglobulins, with human milk oligosaccharides (HMOs) providing additional support by inhibiting pathogen binding to host cell ligands. The prebiotic and immune-modulatory activity of HMOs strongly depends on their structure. Over 200 individual structures have been identified so far, with the composition varying significantly among women. The structure and composition of HMOs are influenced by factors such as the Lewis blood group, secretor status, and the duration of nursing. HMO profiles are heavily influenced by maternal phenotypes, which are defined based on the expression of two specific fucosyltransferases. However, recent data have shown that HMO content can be modified by various factors, both changeable and unchangeable, including diet, maternal age, gestational age, mode of delivery, breastfeeding frequency, and race. The first part of this overview presents the historical background of these sugars and the efforts by scientists to extract them using the latest chromatography methods. The second part is divided into subchapters that examine modifiable and non-modifiable factors, reviewing the most recent articles on HMO composition variations due to specific reasons and summarizing potential future challenges in conducting these types of studies. Full article

Human milk oligosaccharides (HMOs) are complexes that play a crucial role in shaping the early-life gut microbiota. This study intends to explore whether HMO patterns are associated with the gut microbiota of infants. We included 96 Chinese breastfeeding mother–infant dyads. Breast milk and infant faecal samples were collected and tested. With milk 2′-fucosyllactose, difucosyllactose, and lacto-N-fucopentaose-I as biomarkers, we divided the mothers into secretor and non-secretor groups. HMO patterns were extracted using principal component analysis. The majority (70.7%) of mothers were categorised as secretor and five different HMO patterns were identified. After adjustment, the infants of secretor mothers exhibited a lower relative abundance of Bifidobacterium bifidum (β = −0.245, 95%CI: −0.465~−0.025). An HMO pattern characterised by high levels of 3-fucosyllactose, lacto-N-fucopentaose-III, and lacto-N-neodifucohexaose-II was positively associated with the relative abundance of Bifidobacterium breve (p = 0.014), while the pattern characterised by lacto-N-neotetraose, 6′-sialyllactose, and sialyllacto-N-tetraose-b was negatively associated with Bifidobacterium breve (p = 0.027). The pattern characterised by high levels of monofucosyl-lacto-N-hexaose-III and monofucosyl-lacto-N-neohexaose was positively associated with Bifidobacterium dentium (p = 0.025) and Bifidobacterium bifidum (p < 0.001), respectively. This study suggests that HMO patterns from mature breast milk were associated with certain gut microbiota of breastfed infants. Full article

The ABO blood groups, Lewis antigens, and secretor systems are important components of transfusion medicine. These interconnected systems have been also shown to be associated with differing susceptibility to bacterial and viral infections, likely as the result of selection over the course of evolution and the constant tug of war between humans and infectious microbes. This comprehensive narrative review aimed to explore the literature and to present the current state of knowledge on reported associations of the ABO, Lewis, and secretor blood groups with SARS-CoV-2 infection and COVID-19 severity. Our main finding was that the A blood group may be associated with increased susceptibility to SARS-CoV-2 infection, and possibly also with increased disease severity and overall mortality. The proposed pathophysiological pathways explaining this potential association include antibody-mediated mechanisms and increased thrombotic risk amongst blood group A individuals, in addition to altered inflammatory cytokine expression profiles. Preliminary evidence does not support the association between ABO blood groups and COVID-19 vaccine response, or the risk of developing long COVID. Even though the emergency state of the pandemic is over, further research is needed especially in this area since tens of millions of people worldwide suffer from lingering COVID-19 symptoms. Full article

The infant non-secretor histoblood group antigen phenotype is associated with reduced risk of symptomatic rotavirus diarrhea, one of the leading global causes of severe pediatric diarrheal disease and mortality. However, little is known regarding the role of secretor status in asymptomatic rotavirus infections. Therefore, we performed a nested case–control study within a birth cohort study previously conducted in Dhaka, Bangladesh, to determine the association between infant secretor phenotype and the odds of asymptomatic rotavirus infection, in addition to the risk of rotavirus diarrhea, in unvaccinated infants. In the parent cohort, infants were enrolled in the first week of life and followed through the first two years of life with multiple clinic visits and active surveillance for diarrheal illness. Secretor phenotyping was performed on saliva. Eleven surveillance stools collected over the first year of life were tested for rotavirus by real-time RT-PCR, followed by conventional PCR and amplicon sequencing to identify the infecting P-type of positive specimens. Similar to findings for symptomatic diarrhea, infant non-secretors experienced significantly fewer primary episodes of asymptomatic rotavirus infection through the first year of life in a likely rotavirus P-genotype-dependent manner. These data suggest that non-secretors experienced reduced risk from rotavirus due to decreased susceptibility to infection rather than reduced infection severity. Full article

Human milk is abundant in carbohydrates and includes human milk oligosaccharides (HMOs) and N/O-glycans conjugated to proteins. HMO compositions and concentrations vary in individuals according to the maternal secretor status based on the fucosyltransferase 2 genotype; however, the profile of N/O-glycans remains uninvestigated because of the analytical complexity. Herein, we applied a label-free chromatography–mass spectrometry (LC–MS) technique to elucidate the variation in the composition and concentration of N/O-glycans in human milk. We used label-free LC–MS to relatively quantify 16 N-glycans and 12 O-glycans in 200 samples of Japanese human milk (1–2 months postpartum) and applied high performance anion exchange chromatography with pulsed amperometric detection to absolutely quantify the concentrations of 11 representative HMOs. Cluster analysis of the quantitative data revealed that O-glycans and several HMOs were classified according to the presence or absence of fucose linked to galactose while N-glycans were classified into a different group from O-glycans and HMOs. O-glycans and HMOs with fucose linked to galactose were more abundant in human milk from secretor mothers than from nonsecretor mothers. Thus, secretor status influenced the composition and concentration of HMOs and O-glycans but not those of N-glycans in human milk. Full article

α(1,2)fucosyltransferase (Se enzyme) encoded by FUT2 is involved in the secretor status of ABH(O) blood group antigens. The se^del2 allele is one of the non-functional FUT2 (se) alleles in which 9.3 kb, containing the entire coding region of FUT2, is deleted by Alu-mediated nonhomologous recombination. In addition to this allele, three SNPs of FUT2, c.375A>G, c.385A>T, and c.571C>T, appear to be prevalent in certain Oceanian populations such as Polynesians. Recently, we developed an endpoint genotyping assay to determine se^del2 zygosity, using a FAM-labeled probe for detection of the se^del2 allele and a VIC-labeled probe for the detection of FUT2. In this study, instead of the VIC probe, a HEX-labeled probe covering both c.375A>G and c.385A>T and a Cy5-labeled probe covering c.571C>T were added to the se^del2 allele assay mixture to allow for the simultaneous detection of these four variations via endpoint genotyping for se^del2 zygosity and fluorescence melting curve analysis for c.375A>G, c.385A>T, and c.571C>T genotyping. The results obtained from 24 Samoan subjects using this method were identical to those obtained using previous methods. Therefore, it appears that the present method can accurately determine these four variations simultaneously. Full article

Human milk oligosaccharides (HMOs) stimulate the growth of gut commensals, prevent the adhesion of enteropathogens and modulate host immunity. The major factors influencing variations in the HMO profile are polymorphisms in the secretor (Se) or Lewis (Le) gene, which affect the activity of the enzymes fucoslytransferase 2 and 3 (FUT2 and FUT3) that lead to the formation of four major fucosylated and non-fucosylated oligosaccharides (OS). This pilot study aimed to determine the HMO profile of Israeli breastfeeding mothers of 16 term and 4 preterm infants, from a single tertiary center in the Tel Aviv area. Fifty-two human milk samples were collected from 20 mothers at three-time points: colostrum, transitional milk and mature milk. The concentrations of nine HMOs were assessed using liquid chromatography coupled with mass spectra chromatograms. Fifty-five percent of the mothers were secretors and 45% were non-secretors. Infant sex affected HMO levels depending on the maternal secretor status. Secretor mothers to boys had higher levels of FUT2-dependent OS and higher levels of disialyllacto-N-tetraose in the milk of mothers to girls, whereas non-secretor mothers to girls had higher levels of 3′-sialyllactose. In addition, the season at which the human milk samples were obtained affected the levels of some HMOs, resulting in significantly lower levels in the summer. Our findings provide novel information on the irregularity in the HMO profile among Israeli lactating women and identify several factors contributing to this variability. Full article

Human milk oligosaccharides (HMOs) are the third most abundant component in breast milk. HMOs benefit infant gut health, modulate immune responses, and promote brain development. The profile and concentration of HMOs vary considerably among breastfeeding women, and are reported to be associated with genetic, maternal, and environmental factors as well as feeding practices. One reason for the diversity in HMO concentration is the secretor gene, which determines the presence of an enzyme responsible for the synthesis of 2′-FL and LNFP-I. To date, there is no report about HMO concentration or profile in the New Zealand population. Our objective was to investigate 12 HMO concentrations in a small sample of New Zealand women. Sixty-eight breastfeeding mothers (mean age 32 years, 77% Caucasian) of singleton infants (median age [Q1, Q3] 108 [70, 166] days) were included, with 65% exclusively breastfeeding and 54% who had two or more children. Concentrations of 12 HMOs were measured by UHPLC with fluorescence detection. Overall, 68% of mothers were secretors, which was defined by the presence of 2′-FL in the milk. HMO profiles varied widely; total HMO concentration varied 4.2-fold between women; and individual HMOs varied from 4.8-fold to >100-fold. The median of total HMO concentration (Q1, Q3) of the secretors and non-secretors were 6774.9 (6395.4, 8245.6) mg/L and 7128.0 (6093.1, 7880.1) mg/L respectively. Significant differences in concentration of 2′-FL, 3-FL, A-Tet, LNFP-I, LNFP-II, LNFPV, and LNnT between secretors and non-secretors were found by Mann–Whitney tests. However, there was no significant difference in concentrations of LNFP-III, LNnFP, 3′-SL, 6′-SL, LNT, or total HMOs between the secretors and the non-secretors. HMO concentrations vary broadly between breastfeeding women. A longitudinal cohort of a larger sample size is required to fully investigate HMO profiles at different lactation stages of New Zealand women and to further explore the influence of maternal and environmental factors on HMO concentration. Full article

Background: Human milk oligosaccharides (HMOs) are the third most abundant component of human milk. Various factors may affect the concentration of HMOs, such as the lactation period, Lewis blood type, and the maternal secretor gene status. Objectives: The purpose of this study is to investigate factors associated with HMO concentrations in Chinese populations. Methods: A sub-sample of 481 was randomly selected from a large cross-sectional study in China (n = 6481) conducted in eight provinces (Beijing, Heilongjiang, Shanghai, Yunnan, Gansu, Guangdong, Zhejiang, and Shandong) between 2011 and 2013. HMO concentrations were determined by a high-throughput UPLC-MRM method. Various factors were collected through face-to-face interviews. Anthropometric measurement was conducted by trained staff. Results: Median total HMO concentration was 13.6 g/L, 10.7 g/L, and 6.0 g/L for colostrum, transitional milk, and mature milk, respectively. HMO concentration decreased significantly as the lactation period increased (p < 0.0001). There were significant differences of average total HMO concentration between secretor mothers and non-secretor mothers (secretor 11.3 g/L vs. non-secretor 5.8 g/L, p < 0.0001). There were significant differences of average total HMO concentrations among three Lewis blood types (p = 0.003). Comparing with the concentration of total oligosaccharides of Le+ (a−b+), average of total oligosaccharides concentrations increased by 3.9 (Le+ (a+b−), p = 0.004) and 1.1 g/L (Le− (a−b−), p = 0.049). The volume of breast milk expressed and the province the mother came from affected the concentration of total oligosaccharides (all p < 0.0001). Maternal BMI (p = 0.151), age (p = 0.630), prematurity (p = 0.850), mode of delivery (p = 0.486), infants’ gender (p = 0.685), maternal education level (p = 0.989), maternal occupation (p = 0.568), maternal allergic history (p = 0.370), maternal anemia (p = 0.625), pregnancy-induced hypertension (p = 0.739), gestational diabetes (p = 0.514), and parity (p = 0.098) were not significantly correlated with the concentration of milk oligosaccharides. The concentrations of 2′-fucosyllactose (2′-FL), lacto-N-neotetraose (LNnT), sialyllacto-N-tetraose c (LSTc), lacto-N-fucopentaose I (LNFP-I), disialylated lacto-N-tetraose (DSLNT), difucosyl-para-lacto-N-neohexaose (DFpLNnH), difucosyl-lacto-N-hexaose (DFLNH[a]), and 3-sialyllactose (3′-SL) showed a gradual downward trend, while the concentration of 3-fucosyllactose (3-FL) showed a gradual upward trend among three lactation stages (p < 0.05). Conclusions: The concentration of HMOs changes throughout lactation, and it varies between different HMOs. HMO concentrations differed between lactation stage, maternal secretor gene status, Lewis blood type, volume of breast milk expressed, and the province the mother came from. Prematurity, mode of delivery, parity, infants’ gender, and maternal characteristics did not affect the HMO concentration. Geographical region may be not associated with HMOs concentration in human milk. There may be a mechanism for co-regulation of the secretion of some of the oligosaccharides such as 2′FL vs. 3FL, 2′FL vs. LNnT, and lacto-N-tetraose (LNT). Full article

A major polymorphism in the fucosyltransferase2 (FUT2) gene influences risk of multiple gut diseases, but its impact on the microbiome of breastfed infants was unknown. In individuals with an active FUT2 enzyme (“secretors”), the intestinal mucosa is abundantly fucosylated, providing mutualist bacteria with a rich endogenous source of fucose. Non-secretors comprise approximately one-fifth of the population, and they lack the ability to create this enzyme. Similarly, maternal secretor status influences the abundance of a breastfeeding mother’s fucosylated milk oligosaccharides. We compared the impact of maternal secretor status, measured by FUT2 genotype, and infant secretor status, measured by FUT2 genotype and phenotype, on early infant fecal microbiome samples collected from 2-month-old exclusively breastfed infants (n = 59). Infant secretor status (19% non-secretor, 25% low-secretor, and 56% full-secretor) was more strongly associated with the infant microbiome than it was with the maternal FUT2 genotype. Alpha diversity was greater in the full-secretors than in the low- or non-secretor infants (p = 0.049). Three distinct microbial enterotypes corresponded to infant secretor phenotype (p = 0.022) and to the dominance of Bifidobacterium breve, B. longum, or neither (p < 0.001). Infant secretor status was also associated with microbial metabolic capacity, specifically, bioenergetics pathways. We concluded that in exclusively breastfed infants, infant—but not maternal—secretor status is associated with infant microbial colonization and metabolic capacity. Full article