Search Results (16)

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 impact of five human milk oligosaccharides (HMOs)—2′-fucosyllactose (2FL), 3′-sialyllactose (3SL), 6′-sialyllactose (6SL), lacto-N-tetraose (LNT), and lacto-N-neotetraose (LNnT)—on the gut microbiota and short-chain fatty acid (SCFA) metabolites in infants aged 0–6 months was assessed through in vitro fermentation. Analyses of the influence of different HMOs on the composition and distribution of infant gut microbiota and on SCFA levels were conducted using 16S rRNA sequencing, quantitative real-time PCR (qPCR), and gas chromatography (GC), respectively. The findings indicated the crucial role of the initial microbiota composition in shaping fermentation outcomes. Fermentation maintained the dominant genera species in the intestine but influenced their abundance and distribution. Most of the 10 Bifidobacteria strains effectively utilized HMOs or their degradation products, particularly demonstrating proficiency in utilizing 2FL and sialylated HMOs compared to non-fucosylated neutral HMOs. Moreover, our study using B. infantis-dominant strains and B. breve-dominant strains as inocula revealed varying acetic acid levels produced by Bifidobacteria upon HMO degradation. Specifically, the B. infantis-dominant strain yielded notably higher acetic acid levels than the B. breve-dominant strain (p = 0.000), with minimal propionic and butyric acid production observed at fermentation’s conclusion. These findings suggest the potential utilization of HMOs in developing microbiota-targeted foods for infants. Full article

Human milk oligosaccharides (HMOs) are a major component of human milk. They are associated with multiple health benefits and are manufactured on a large scale for their addition to different food products. In this systematic review, we evaluate the health outcomes of published clinical trials involving the supplementation of manufactured HMOs. We screened the PubMed database and Cochrane Library, identifying 26 relevant clinical trials and five publications describing follow-up studies. The clinical trials varied in study populations, including healthy term infants, infants with medical indications, children, and adults. They tested eight different HMO structures individually or as blends in varying doses. All trials included safety and tolerance assessments, and some also assessed growth, stool characteristics, infections, gut microbiome composition, microbial metabolites, and biomarkers. The studies consistently found that HMO supplementation was safe and well tolerated. Infant studies reported a shift in outcomes towards those observed in breastfed infants, including stool characteristics, gut microbiome composition, and intestinal immune markers. Beneficial gut health and immune system effects have also been observed in other populations following HMO supplementation. Further clinical trials are needed to substantiate the effects of HMO supplementation on human health and to understand their structure and dose dependency. Full article

Breastmilk is the optimal source of infant nutrition, with short-term and long-term health benefits. Some of these benefits are mediated by human milk oligosaccharides (HMOs), a unique group of carbohydrates representing the third most abundant solid component of human milk. We performed the first clinical study on infant formula supplemented with five different HMOs (5HMO-mix), comprising 2′-fucosyllactose, 3-fucosyllactose, lacto-N-tetraose, 3′-sialyllactose and 6′-sialyllactose at a natural total concentration of 5.75 g/L, and here report the analysis of the infant fecal microbiome. We found an increase in the relative abundance of bifidobacteria in the 5HMO-mix cohort compared with the formula-fed control, specifically affecting bifidobacteria that can produce aromatic lactic acids. 5HMO-mix influenced the microbial composition as early as Week 1, and the observed changes persisted to at least Week 16, including a relative decrease in species with opportunistic pathogenic strains down to the level observed in breastfed infants during the first 4 weeks. We further analyzed the functional potential of the microbiome and observed features shared between 5HMO-mix-supplemented and breastfed infants, such as a relative enrichment in mucus and tyrosine degradation, with the latter possibly being linked to the aromatic lactic acids. The 5HMO-mix supplement, therefore, shifts the infant fecal microbiome closer to that of breastfed infants. 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 complex nonnutritive sugars present in human milk. These sugars possess prebiotic, immunomodulatory, and antagonistic properties towards pathogens and therefore are important for the health and well-being of newborn babies. Lower prevalence of breastfeeding around the globe, rising popularity of nutraceuticals, and low availability of HMOs have inspired efforts to develop economically feasible and efficient industrial-scale production platforms for HMOs. Recent progress in synthetic biology and metabolic engineering tools has enabled microbial systems to be a production system of HMOs. In this regard, the model organism Escherichia coli has emerged as the preferred production platform. Herein, we summarize the remarkable progress in the microbial production of HMOs and discuss the challenges and future opportunities in unraveling the scope of production of complex HMOs. We focus on the microbial production of five HMOs that have been approved for their commercialization. Full article

The objective of this narrative review was to synthesize the literature on human milk oligosaccharides (HMOs) and neurodevelopmental outcomes in human milk-fed infants. We conducted a scoping review of the literature indexed in PubMed reporting observational or interventional studies on HMO exposure in relation to psychometric measures in infants. Studies were characterized based on study design and definitions of HMO exposure and neurodevelopmental outcomes. Six studies were identified; all were observational in design, and five were conducted in full-term infants. Sample sizes ranged from 35–659 infants. HMOs were defined as individual concentrations or relative abundances assessed at 1 and/or 6 months of age. Studies accounted for differences in HMO exposure based on maternal secretor status. Neurodevelopmental outcomes were assessed between 6 and 24 months of age and included four domains. Studies in full-term infants reported that total and individual fucosylated and sialylated HMOs were positively associated with cognitive, language, and motor skill domains between 18 and 24 months of age, while the single study in preterm infants reported no statistically significant findings in the full cohort. The presence of a maternal secretor did not consistently alter the associations between HMO exposure and neurodevelopmental outcomes. Emerging evidence from observational studies suggests that HMO exposure may be beneficial for neurodevelopment in infants. Full article

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. Full article

Human milk provides neonates with various components that ensure newborns’ growth, including protection from bacterial and viral infections. In neonates, the biological functions of many breast milk components can be very different compared with their functions in the body fluids of healthy adults. Catalytic antibodies (abzymes) that hydrolyze peptides, proteins, DNAs, RNAs, and oligosaccharides were detected, not only in the blood sera of autoimmune patients, but also in human milk. Non-coding microRNAs (18–25 nucleotides) are intra- and extracellular molecules of different human fluids. MiRNAs possess many different biological functions, including the regulation of several hundred genes. Five of them, miR-148a-3p, miR-200c-3p, miR-378a-3p, miR-146b-5p, and let-7f-5p, were previously found in milk in high concentrations. Here, we determined relative numbers of miRNA copies in 1 mg of analyzed cells, lipid fractions, and plasmas of human milk samples. The relative amount of microRNA decreases in the following order: cells ≈ lipid fraction > plasma. IgGs and sIgAs were isolated from milk plasma, and their activities in the hydrolysis of five microRNAs was compared. In general, sIgAs demonstrated higher miRNA-hydrolyzing activities than IgGs antibodies. The hydrolysis of five microRNAs by sIgAs and IgGs was site-specific. The relative activity of each microRNA hydrolysis was very dependent on the milk preparation. The correlation coefficients between the contents of five RNAs in milk plasma, and the relative activities of sIgAs compared to IgGs in hydrolyses, strongly depended on individual microRNA, and changed from −0.01 to 0.80. Thus, it was shown that milk contains specific antibodies (abzymes) that hydrolyze microRNAs specific for human milk. Full article

Background: Five of the most abundant human milk oligosaccharides (HMOs) in human milk are 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL). Methods: A randomized, double-blind, controlled parallel feeding trial evaluated growth in healthy term infants fed a control milk-based formula (CF; n = 129), experimental milk-based formula (EF; n = 130) containing five HMOs (5.75 g/L; 2′-FL, 3-FL, LNT, 3′-SL and 6′-SL) or human milk (HM; n = 104). Results: No significant differences (all p ≥ 0.337, protocol evaluable cohort) were observed among the three groups for weight gain per day from 14 to 119 days (D) of age, irrespective of COVID-19 or combined non-COVID-19 and COVID-19 periods. There were no differences (p ≥ 0.05) among the three groups for gains in weight and length from D14 to D119. Compared to the CF group, the EF group had more stools that were soft, frequent and yellow and were similar to the HM group. Serious and non-serious adverse events were not different among groups, but more CF-fed infants were seen by health care professionals for illness from study entry to D56 (p = 0.044) and D84 (p = 0.028) compared to EF-fed infants. Conclusions: The study demonstrated that the EF containing five HMOs supported normal growth, gastrointestinal (GI) tolerance and safe use in healthy term infants. Full article

The aim of this systematic review was to summarize concentrations of human milk oligosaccharides (HMOs) in the Chinese population. We searched articles originally published in both Chinese and English. When compiling data, lactation was categorized into five stages. We found that 6′-sialyllactose, lacto-N-tetraose, and lacto-N-neotetraose decreased over lactation. Conversely, 3′-fucosyllactose increased over lactation. Our study represents the first systematic review to summarize HMO concentrations in Chinese population. Our findings not only provide data on HMO profiles in Chinese population but suggest future directions in the study of the metabolism of HMOs. Full article

Human milk oligosaccharides (HMOs) are complex sugars that occur naturally in human breast milk and provide many beneficial functions. Most formula products lack HMOs or contain only the most abundant HMO, 2′-fucosyllactose; however, benefits of HMOs come from multiple sugars. We therefore developed a mixture of five HMOs (5HMO-Mix) mimicking the natural concentrations of the top five HMOs (5.75 g/L total, comprising 52% 2′-fucosyllactose, 13% 3-fucosyllactose, 26% lacto-N-tetraose, 4% 3′-sialyllactose, and 5% 6′-sialyllactose) representing the groups of neutral, neutral-fucosylated, and sialylated HMOs. We conducted the first multicenter, randomized, controlled, parallel-group clinical study assessing the safety, tolerability, and effect on growth of formula containing the 5HMO-Mix in healthy infants. We enrolled 341 subjects aged ≤14 days; 225 were randomized into groups fed either with infant formula containing 5HMO-Mix (5HMO-Mix) or infant formula without HMOs (IF) for 4 months, with the others exclusively breastfed. There were no differences in weight, length, or head circumference gain between the two formula groups. The 5HMO-Mix was well tolerated, with 5HMO-Mix and breastfed infants producing softer stools at a higher stool frequency than the control formula group. Adverse events were equivalent in all groups. We conclude that the 5HMO-Mix at 5.75 g/L in infant formula is safe and well tolerated by healthy term infants during the first months of life. Full article

Bifidobacterium longum subsp. infantis (B. infantis) is one of a few microorganisms capable of metabolizing human breast milk and is a pioneer colonizer in the guts of breastfed infants. One current challenge is differentiating B. infantis from its close relatives, B. longum and B. suis. All three organisms are classified in the same species group but only B. infantis can metabolize human milk oligosaccharides (HMOs). We compared HMO-metabolizing genes across different Bifidobacterium genomes and developed B. infantis-specific primers to determine if the genes alone or the primers can be used to quickly characterize B. infantis. We showed that B. infantis is uniquely identified by the presence of five HMO-metabolizing gene clusters, tested for its prevalence in infant gut metagenomes, and validated the results using the B. infantis-specific primers. We observed that only 15 of 203 (7.4%) children under 2 years old from a cohort of US children harbored B. infantis. These results highlight the importance of developing and improving approaches to identify B. infantis. A more accurate characterization may provide insights into regional differences of B. infantis prevalence in infant gut microbiota. Full article

The ability of bacteria to adhere to the intestinal mucosa is a critical property necessary for the long-term colonization of the intestinal tract. This ability can be highly sensitive to the presence of prebiotics. However, limited data are available in this respect for beneficial bacteria such as probiotics or resident gut microbiota. We previously demonstrated that the presence of prebiotics may decrease adherence in several pre- and probiotic combinations. Thus, characterizing the interactions between numerous combinations involving different classes of pre- and probiotics can be crucial in identifying new synbiotics. Accordingly, here, we extend our prior analyses to evaluate the adhesion of five lactobacilli, six bifidobacteria, and one probiotic Escherichia coli strains, as commercial probiotics or promising probiotic candidates, together with the cariogenic Bifidobacterium dentium strain. As an in vitro intestinal mucosa model, Caco-2 and mucin-secreting HT29-MTX cells were co-cultured at 9:1 in the presence or absence of prebiotics. Commercial inulin-type fructooligosaccharide prebiotics Orafti^® GR, Orafti^® P95, and galactooligosaccharide-based prebiotic formula Vivinal^®, including purified human milk oligosaccharides (HMOs) were added into the cultivation media as the sole sugar source (2.5% each). Adherence was tested using microtiter plates and was evaluated as the percentage of fluorescently labeled bacteria present in the wells after three washes. Consistent prebiotics-mediated enhanced adherence was observed only for the commercial probiotic strain E. coli O83. For the remaining strains, the presence of HMO or prebiotics Orafti^® P95 or Orafti^® GR decreased adherence, reaching statistical significance (p < 0.05) for three of out of eight (HMO) or five of out of 11 strains tested, respectively. Conversely, Vivinal^® enhanced adhesion in six out of the 12 strains tested, and notably, it significantly attenuated the adherence of the cariogenic Bifidobacterium dentium Culture Collection of Dairy Microorganisms (CCDM) 318. To our knowledge, this represents the first report on the influence of commercial prebiotics and HMOs on the adhesion of the cariogenic Bifidobacterium sp. Vivinal^® seems to be a promising prebiotic to be used in the formulation of synbiotics, supporting the adhesion of a wide range of probiotics, especially the strains B. bifidum BBV and BBM and the probiotic Escherichia coli O83. Full article

Because of the recognized health benefits of breast milk, it is recommended as the sole nutrition source during the first 6 months of life. Among the bioactive components are human milk oligosaccharides (HMOs) that exert part of their activity via the gut microbiota. Here, we investigated the gut microbiota fermentation of HMO 2’fucosyllactose (2’-FL), using two in vitro models (48 h fecal incubations and the long-term mucosal simulator of the human intestinal microbial ecosystem [M-SHIME^®]) with fecal samples from 3-month-old breastfed (BF) infants as well as 2–3 year old toddlers. The short-term model allowed the screening of five donors for each group and provided supportive data for the M-SHIME^® study. A key finding was the strong and immediate increase in the relative abundance of Bifidobacteriaceae following 2’-FL fermentation by both the BF infant and toddler microbiota in the M-SHIME^®. At the metabolic level, while decreasing branched-chain fatty acids, 2’-FL strongly increased acetate production together with increases in the health-related propionate and butyrate whilst gas production only mildly increased. Notably, consistently lower gas production was observed with 2’-FL fermentation as compared to lactose, suggesting that reduced discomfort during the dynamic microbiome establishment in early life may be an advantage along with the bifidogenic effect observed. Full article