Bovine Milk Oligosaccharides and Human Milk Oligosaccharides Modulate the Gut Microbiota Composition and Volatile Fatty Acid Concentrations in a Preclinical Neonatal Model.
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SUBMITTER: Wang M
PROVIDER: S-EPMC8143120 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Neonatal rotavirus infections are predominantly asymptomatic. While an association with gastrointestinal symptoms has been described in some settings, factors influencing differences in clinical presentation are not well understood. Using multidisciplinary approaches, we show that a complex interplay between human milk oligosaccharides (HMOs), milk microbiome, and infant gut microbiome impacts neonatal rotavirus infections. Validating in vitro studies where HMOs are not decoy receptors for neonatal strain G10P[11], population studies show significantly higher levels of Lacto-N-tetraose (LNT), 2'-fucosyllactose (2'FL), and 6'-siallylactose (6'SL) in milk from mothers of rotavirus-positive neonates with gastrointestinal symptoms. Further, these HMOs correlate with abundance of Enterobacter/Klebsiella in maternal milk and infant stool. Specific HMOs also improve the infectivity of a neonatal strain-derived rotavirus vaccine. This study provides molecular and translational insight into host factors influencing neonatal rotavirus infections and identifies maternal components that could promote the performance of live, attenuated rotavirus vaccines.
| S-EPMC6258677 | biostudies-other
Project description:Human milk is a complex and variable ecosystem fundamental to the development of newborns. This study aimed to investigate relationships between human milk oligosaccharides (HMO) and human milk bacterial profiles and infant body composition. Human milk samples (n = 60) were collected at two months postpartum. Infant and maternal body composition was measured with bioimpedance spectroscopy. Human milk bacterial profiles were assessed using full-length 16S rRNA gene sequencing and 19 HMOs were quantitated using high-performance liquid chromatography. Relative abundance of human milk bacterial taxa were significantly associated with concentrations of several fucosylated and sialylated HMOs. Individual human milk bacteria and HMO intakes and concentrations were also significantly associated with infant anthropometry, fat-free mass, and adiposity. Furthermore, when data were stratified based on maternal secretor status, some of these relationships differed significantly among infants born to secretor vs non-secretor mothers. In conclusion, in this pilot study the human milk bacterial profile and HMO intakes and concentrations were significantly associated with infant body composition, with associations modified by secretor status. Future research designed to increase the understanding of the mechanisms by which HMO and human milk bacteria modulate infant body composition should include intakes in addition to concentrations.
| S-EPMC8911220 | biostudies-literature
Project description:Consumption of mothers' milk is associated with reduced incidence and severity of enteric infections, leading to reduced morbidity in breastfed infants. Fucosylated and sialylated human milk oligosaccharides (HMO) are important for both direct antimicrobial action - likely via a decoy effect - and indirect antimicrobial action through commensal growth enhancement. Bovine milk oligosaccharides (BMO) are a potential source of HMO-mimics as BMO resemble HMO; however, they have simpler and less fucosylated structures. BMO isolated at large scales from bovine whey permeate were modified by the addition of fucose and/or sialic acid to generate HMO-like glycans using high-yield and cost-effective one-pot multienzyme approaches. Quadrupole time-of-flight LC/MS analysis revealed that 22 oligosaccharides were synthesized and 9 had identical composition to known HMO. Preliminary anti-adherence activity assays indicated that fucosylated BMO decreased the uptake of enterohemorrhagic Escherichia coli O157:H7 by human intestinal epithelial Caco-2 cells more effectively than native BMO.
| S-EPMC7034812 | biostudies-literature
Project description:Oligosaccharides support gut development and bacterial colonization in term infants, but it is unknown if they benefit preterm infants. Using preterm pigs, we investigated effects of bovine milk supplements enriched with oligosaccharides to improve gut development and colonization. Caesarean-delivered preterm pigs (n = 57) were reared for 19 days. The pigs were fed bovine milk supplemented with an oligosaccharide-enriched whey containing sialyllactose, or a heterogeneous oligosaccharide ingredient. To evaluate the influence of artificial rearing, near-term, vaginally born pigs raised by their sow (n = 12) were compared with artificially reared, caesarean-delivered near-term pigs (n = 14). In preterm pigs, the clinical outcome, gut function, gut microbiota, and systemic immunity were similar among dietary treatments. Natural rearing increased growth rates, gut functions, colon short chain fatty acid concentrations and bacterial diversity, relative to artificial rearing. In conclusion, supplements with bovine milk oligosaccharides were well tolerated, but did not improve gut maturation or clinical outcomes in artificially reared preterm piglets. Immaturity at birth, coupled with artificial rearing, may render the neonate unresponsive to the gut-protective effects of milk oligosaccharides. Whether bovine milk oligosaccharides may affect other endpoints (e.g., brain functions) in conditions of immaturity remains to be investigated.
| S-EPMC6213258 | biostudies-literature
Project description:BackgroundThe relationship between human milk oligosaccharides (HMO) and child growth has been investigated only insufficiently with ambiguous results. Therefore, this study examines potential influencing factors of HMO concentrations and how HMO are associated with child growth parameters.MethodsMilk samples from the German LIFE Child cohort of healthy children were analyzed for 9 HMO. Putative associations with maternal and child cofactors and child height, head circumference and BMI between 3 months and 7 years of age were examined. Secretor status, defined as the presence of 2'-fucosyllactose, was investigated for associations with infant outcomes.ResultsOur population consisted of 21 (14.7%) non-secretor and 122 (85.3%) secretor mothers. Maternal age was significantly associated with higher 3'SL concentrations; gestational age was associated with LNT, 6'SL and LNFP-I. Pre-pregnancy BMI was negatively associated with LNnT only in non-secretors. The growth velocity of non-secretors' children was inversely associated with LNnT at 3 months to 1 year (R = 0.95 [0.90, 0.99], p = 0.014), 1 to 2 years (R = 0.80 [0.72, 0.88], p < 0.001) and 5 to 6 years (R = 0.71 [0.57, 0.87], p = 0.002). 2'FL was negatively associated with BMI consistently, reaching statistical significance at 3 months and 4 and 5 years. Children of non-secretors showed higher BMI at 3 months, 6 months, and 3, 6, and 7 years of age.ConclusionWe found that some associations between HMO and infant growth may extend beyond the infancy and breastfeeding periods. They highlight the importance of both maternal and infant parameters in the understanding of the underlying associations.Trial registrationThe study is registered with ClinicalTrial.gov: NCT02550236 .
| S-EPMC8556924 | biostudies-literature
Project description:Human milk contains over 200 distinct oligosaccharides, which are critical to shaping the developing neonatal gut microbiome. To investigate whether a complex mixture of human milk oligosaccharides (HMOs) would similarly modulate the adult gut microbiome, HMO-Concentrate derived from pooled donor breast milk was administered orally to 32 healthy adults for 7 days followed by 21 days of monitoring. Fecal samples were collected for 16S rRNA gene sequencing, shotgun metagenomics, and metabolomics analyses. HMO-Concentrate induced dose-dependent Bifidobacterium expansion, reduced microbial diversity, and altered microbial gene content. Following HMO cessation, a microbial succession occurred with diverse taxonomic changes-including Bacteroides expansion-that persisted through day 28. This was associated with altered microbial gene content, shifts in serum metabolite levels, and increased circulating TGFβ and IL-10. Incubation of cultured adult microbiota with HMO-Concentrate induced dose-dependent compositional shifts that were not recapitulated by individual HMOs or defined mixtures of the 10 most abundant HMOs in HMO-Concentrate at their measured concentrations. These findings support that pooled donor HMOs can exert direct effects on adult gut microbiota and that complex mixtures including low abundance HMOs present in donor milk may be required for maximum effect.Registration: ClinicalTrials.gov NCT05516225.
| S-EPMC10471580 | biostudies-literature
Project description:ContextOligosaccharides are the third largest solid component in human milk. These diverse compounds are thought to have numerous beneficial functions in infants, including protection against infectious diseases. The structures of more than 100 oligosaccharides in human milk have been elucidated so far.ObjectiveThe aim of this review was to identify the main factors that affect the concentrations of oligosaccharides in human milk and to determine whether it is possible to calculate representative and reliable mean concentrations.Data sourcesA comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed.Study selectionThe initial search resulted in 1363 hits. After the elimination of duplicates, the literature was screened. The application of strict inclusion criteria resulted in 21 articles selected.Data extractionOligosaccharide concentrations, both mean values and single values, reported in the literature were sorted by gestational age, secretor status of mothers, and defined lactation periods.ResultsMean concentrations, including confidence limits, of 33 neutral and acidic oligosaccharides reported could be calculated. Concentrations of oligosaccharides in human milk show variations that are dependent on both the secretor type of the mother and the lactation period as examined by analyses of variance. In addition, large interlaboratory variations in the data were observed.ConclusionsWorldwide interlaboratory quantitative analyses of identical milk samples would be required to identify the most reliable methods of determining concentrations of oligosaccharides in human milk. The data presented here contribute to the current knowledge about the composition and quantities of oligosaccharides in human milk and may foster greater understanding of the biological functions of these compounds.
| S-EPMC5914348 | biostudies-literature
Project description:Optimal nutrition is important after preterm birth to facilitate normal brain development. Human milk is rich in sialic acid and preterm infants may benefit from supplementing formula with sialyllactose to support neurodevelopment. Using pigs as models, we hypothesized that sialyllactose supplementation improves brain development after preterm birth. Pigs (of either sex) were delivered by cesarean section at 90% gestation and fed a milk diet supplemented with either an oligosaccharide-enriched whey with sialyllactose (n = 20) or lactose (n = 20) for 19 days. Cognitive performance was tested in a spatial T-maze. Brains were collected for ex vivo magnetic resonance imaging (MRI), gene expression, and sialic acid measurements. For reference, term piglets (n = 14) were artificially reared under identical conditions and compared with vaginally born piglets naturally reared by the sow (n = 12). A higher proportion of sialyllactose supplemented preterm pigs reached the T-maze learning criteria relative to control preterm pigs (p < 0.05), and approximated the cognition level of term reference pigs (p < 0.01). Furthermore, supplemented pigs had upregulated genes related to sialic acid metabolism, myelination, and ganglioside biosynthesis in hippocampus. Sialyllactose supplementation did not lead to higher levels of sialic acid in the hippocampus or change MRI endpoints. Contrary, these parameters were strongly influenced by postconceptional age and postnatal rearing conditions. In conclusion, oligosaccharide-enriched whey with sialyllactose improved spatial cognition, with effects on hippocampal genes related to sialic acid metabolism, myelination, and ganglioside biosynthesis in preterm pigs. Dietary sialic acid enrichment may improve brain development in infants.
| S-EPMC6628371 | biostudies-literature
Project description:BackgroundAlthough bovine milk is regarded as healthy and nutritious, its high content of saturated fatty acids (FA) may be harmful to cardiovascular health. Palmitic acid (C16:0) is the predominant saturated FA in milk with adverse health effects that could be countered by substituting it with higher levels of unsaturated FA, such as oleic acid (C18:1cis-9). In this work, we performed genome-wide association analyses for milk fatty acids predicted from FTIR spectroscopy data using 1811 Norwegian Red cattle genotyped and imputed to a high-density 777k single nucleotide polymorphism (SNP)-array. In a follow-up analysis, we used imputed whole-genome sequence data to detect genetic variants that are involved in FTIR-predicted levels of C16:0 and C18:1cis-9 and explore the transcript profile and protein level of candidate genes.ResultsGenome-wise significant associations were detected for C16:0 on Bos taurus (BTA) autosomes 11, 16 and 27, and for C18:1cis-9 on BTA5, 13 and 19. Closer examination of a significant locus on BTA11 identified the PAEP gene, which encodes the milk protein β-lactoglobulin, as a particularly attractive positional candidate gene. At this locus, we discovered a tightly linked cluster of genetic variants in coding and regulatory sequences that have opposing effects on the levels of C16:0 and C18:1cis-9. The favourable haplotype, linked to reduced levels of C16:0 and increased levels of C18:1cis-9 was also associated with a marked reduction in PAEP expression and β-lactoglobulin protein levels. β-lactoglobulin is the most abundant whey protein in milk and lower levels are associated with important dairy production parameters such as improved cheese yield.ConclusionsThe genetic variants detected in this study may be used in breeding to produce milk with an improved FA health-profile and enhanced cheese-making properties.
| S-EPMC9137198 | biostudies-literature
Project description:Polyunsaturated fatty acids (PUFAs) play a role in a wide variety of physiological processes. They are produced by a series of desaturation and elongation reactions. ? -6-desaturase is a membrane-bound enzyme that catalyzes the conversion of ? -linolenic acid (C18:3 n -3) and linoleic acid (C18:2 n -6) to stearidonic acid (18:4 n -3) and ? -linolenic acid (18:3 n -6). It is encoded by the FADS2 gene located on bovine chromosome 29. The aim of this study was to identify a single nucleotide polymorphism in the FADS2 gene and to determine possible associations with milk fatty acid composition in two breeds of dairy cattle, i.e., Jersey and Polish Holstein-Friesian. Direct DNA sequencing revealed the presence of an A-to-G substitution in intron 3 of the FADS2 gene (rs209202414). Both populations were genotyped with an appropriate PCR-RFLP assay. The following genotype distributions were observed: for Jerseys, AA? = ?0.24, AG? = ?0.63, and GG? = ?0.13; for Polish Holstein-Friesians, AA? = ?0.17, AG? = ?0.40, and GG? = ?0.43. In Jerseys, statistically significant relationships were found between the FASD2 genotypes and the following milk fatty acids: lauric ( P=0.0486 ), behenic ( P=0.0199 ), lignoceric ( P=0.0209 ), oleic ( P=0.0386 ), eicosatrienoic ( P=0.0113 ), and docosadienoic ( P=0.0181 ). In Polish Holstein-Friesian cows, significant associations were observed for erucic ( P=0.0460 ) and docosahexaenoic ( P=0.0469 ) acids. The study indicated the A-to-G substitution (rs209202414) in the bovine FADS2 gene as a potential genetic marker for fatty acid composition in cattle milk.
| S-EPMC6852874 | biostudies-literature