Dietary Isomers of Sialyllactose Increase Ganglioside Sialic Acid Concentrations in the Corpus Callosum and Cerebellum and Modulate the Colonic Microbiota of Formula-Fed Piglets

Jacobi, Sheila K.; Yatsunenko, Tanya; Li, Dongpei; Dasgupta, Somsankar; Yu, Robert K.; Berg, Brian M.; Chichlowski, Maciej; Odle, Jack

doi:10.3945/jn.115.220152

Cited by 113 publications

(115 citation statements)

References 65 publications

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“…Oligosaccharides are increasingly recognized as bioactive components of milk, and are believed to have an impact on the early development of the neonate [22]. Sialic acid-containing oligosaccharides have been implicated in inhibition of pathogen adhesion to host cells, immune system maturation, brain development, and modulation of the gut microbiota [23][24][25]. For example, 6 -SL was shown to reduce rotavirus (RV) infectivity in vitro at concentration levels of 2 to 6 mg/mL [26].…”

Section: Discussionmentioning

confidence: 99%

“…In terms of cognitive development, 6 -SL is an integral component of gangliosides and signaling molecules in the brain, and studies have suggested an association between sialic acid-bound gangliosides and glycoproteins with improved learning ability [28,29]. Jacobi et al [23] reported that formula supplementation with 2 g/L 6 -SL significantly increased the ganglioside-bound SA content in the corpus callosum of pigs compared to piglets receiving non-supplemented formula. Furthermore, Jacobi et al [23] demonstrated a prebiotic action of 6 -SL to modulate the gut microbiome [23].…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of 6′-Sialyllactose Sodium Salt Supplementation to Formula on Growth and Clinical Parameters in Neonatal Piglets

Monaco

Kim²,

Gurung³

et al. 2020

Nutrients

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Oligosaccharides are complex, non-digestible glycans found in large abundance in human milk. The abundance and the profile of bovine milk oligosaccharides and bovine milk based in infant formula differ from those in human milk. Recently, some human milk oligosaccharides (HMOs) have been supplemented to infant formula, however, not all forms have been available in large scale. The objective of the study was to investigate the dose-dependent effects of an enzymatically-synthesized 6′-sialyllactose (6′-SL) sodium salt supplemented to swine milk replacer on growth, hematological parameters, and organ microscopic assessment in our pre-clinical neonatal pig model. Two-day-old male and female pigs (n = 47) were provided one of four experimental diets for 21 days. Diets were formulated to contain 0 (CON), 300 (LOW), 600 (MOD), or 1200 (HIGH) mg/L of 6′-SL sodium salt. On days 8 and 22, samples were collected for hematological and histological analyses. Supplemental 6′-SL sodium salt at all doses supported growth and development comparable to those observed in control animals. In addition, serum chemistries, hematology, and organ microscopic structure were unaffected by 6′-SL (p > 0.05). Thus, addition of enzymatically-synthesized 6′-SL to a milk replacer formula supported growth and clinical outcomes similar to the control formula in the neonatal piglet.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evaluation of 6′-Sialyllactose Sodium Salt Supplementation to Formula on Growth and Clinical Parameters in Neonatal Piglets

Monaco

Kim²,

Gurung³

et al. 2020

Nutrients

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“…Accordingly, SA supplementation in piglets has been shown to influence gene expression for neural cell adhesion molecules (16) and enhance learning and memory (7). Supplementation of sialyllactose increased ganglioside bound SA in the corpus callosum of piglets (17). Provided the multitude of ways in which SA supplementation influences infant development, there is interest in characterizing changes in free and bound SA in expressed milk throughout lactation.…”

Section: Introductionmentioning

confidence: 99%

Porcine Milk Oligosaccharides and Sialic Acid Concentrations Vary Throughout Lactation

et al. 2016

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BackgroundMilk oligosaccharides (OSs) are bioactive components known to influence neonatal development. These compounds have specific physiological functions acting as prebiotics, immune system modulators, and enhancing intestine and brain development.ObjectivesThe pig is a commonly used model for studying human nutrition, and there is interest in quantifying OS composition of porcine milk across lactation compared with human milk. In this study, we hypothesized that OS and sialic acid (SA) composition of porcine milk would be influenced by stage of lactation.MethodsUp to 250 mL of milk were collected from seven sows at each of three time points: day 0 (colostrum), days 7–9 (mature), and days 17–19 (weaning). Colostrum was collected within 6 h of farrowing and 3-day intervals were used for mature and weaning milk to ensure representative sampling. Milk samples were analyzed for OS profiles by Nano-LC Chip–QTOF MS, OS concentrations via HPAEC-PAD, and SA (total and free) was assessed by enzymatic reaction fluorescence detection.ResultsSixty unique OSs were identified in porcine milk. Neutral OSs were the most abundant at each lactation stage (69–81%), followed by acidic-sialylated OSs (16–29%) and neutral-fucosylated OSs (2–4%). As lactation progressed, acidic OSs decreased (P = 0.003), whereas neutral-fucosylated (P < 0.001) and neutral OSs (P = 0.003) increased throughout lactation. Six OSs were present in all samples analyzed across lactation [lacto-N-difucohexaose I (LNDFH-I), 2′-fucosyllactose (2′-FL), lacto-N-fucopentaose I (LNFP-I), lacto-N-neohexaose (LNnH), α1-3,β-4-d-galactotriose (3-Hex), 3′-sialyllactose (3′-SL)], while LDFT was present only in colostrum samples. Analysis of individual OS concentrations indicated differences (P = 0.023) between days 0 and 7. Conversely, between days 7 and 18, OS concentrations remained stable with only LNnH (P < 0.001) and LNDFH-I (P = 0.002) decreasing over this period. Analysis of free SA indicated a decrease (P < 0.001) as lactation progressed, while bound (P < 0.001) and total (P < 0.001) SA increased across lactation.ConclusionConcentrations of OS differ between colostrum and mature milk in the pig, and SA concentrations shift from free to bound forms as lactation progresses. Our results suggest that although porcine milk OS concentration and the number of structures is lower than human milk, the OS profile appears to be closer to human milk rather than to bovine milk, based on previously published profiles.

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“…Feeding rat pups and piglets with a diet rich in SA is reported to upregulate expression of the learning genes Gne and ST8SiaIV, and to promote cognitive functioning, which should be confirmed in further experiments. Also, whether SA or sialyl‐lactose is incorporated into brain gangliosides as reported needs to be confirmed in further studies …”

Section: Functions Of Hmosmentioning

confidence: 93%

Human Milk Oligosaccharides as Promising Antivirals

Morozov

Hansman

Hanisch

et al. 2018

Molecular Nutrition Food Res

107

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Human milk oligosaccharides (HMOs) are diverse unconjugated carbohydrates that are highly abundant in human breast milk. These glycans are investigated in the context of exhibiting multiple functions in infant growth and development. They seem to provide protection against infectious diseases, including a number of poorly manageable viral infections. Although the potential mechanism of the HMO antiviral protection is rather broad, much of the current experimental work has focused on studying of HMO antiadhesive properties. HMOs may mimic structures of viral receptors and block adherence to target cells, thus preventing infection. Still, the potential of HMOs as a source for new antiviral drugs is relatively unexploited. This can be partly attributed to the extreme complexity of the virus-carbohydrate interactions and technical difficulties in HMO isolation, characterization, and manufacturing procedures. Fortunately, we are currently entering a period of major technological advances that have enabled deeper insights into carbohydrate mediated viral entry, rational selection of HMOs as anti-entry inhibitors, and even evaluation of individual synthetic HMO structures. Here, we provide an up-to-date review on glycan binding studies for rotaviruses, noroviruses, influenza viruses, and human immunodeficiency viruses. We also discuss the preventive and therapeutic potential of HMOs as anti-entry inhibitors and address challenges on the route from fundamental studies to clinical trials.

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Dietary Isomers of Sialyllactose Increase Ganglioside Sialic Acid Concentrations in the Corpus Callosum and Cerebellum and Modulate the Colonic Microbiota of Formula-Fed Piglets

Cited by 113 publications

References 65 publications

Evaluation of 6′-Sialyllactose Sodium Salt Supplementation to Formula on Growth and Clinical Parameters in Neonatal Piglets

Evaluation of 6′-Sialyllactose Sodium Salt Supplementation to Formula on Growth and Clinical Parameters in Neonatal Piglets

Porcine Milk Oligosaccharides and Sialic Acid Concentrations Vary Throughout Lactation

Human Milk Oligosaccharides as Promising Antivirals

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