Evolution of milk oligosaccharides: Origin and selectivity of the ratio of milk oligosaccharides to lactose among mammals.

BACKGROUND: The carbohydrate fraction of mammalian milk is constituted of lactose and oligosaccharides, most of which contain a lactose unit at their reducing ends. Although lactose is the predominant saccharide in the milk of most eutherians, oligosaccharides significantly predominate over lactose in the milk of monotremes and marsupials. SCOPE OF REVIEW: This review describes the most likely process by which lactose and milk oligosaccharides were acquired during the evolution of mammals and the mechanisms by which these saccharides are digested and absorbed by the suckling neonates. MAJOR CONCLUSIONS: During the evolution of mammals, c-type lysozyme evolved to α-lactalbumin. This permitted the biosynthesis of lactose by modulating the substrate specificity of ß4galactosyltransferase 1, thus enabling the concomitant biosynthesis of milk oligosaccharides through the activities of several glycosyltransferases using lactose as an acceptor. In most eutherian mammals the digestion of lactose to glucose and galactose is achieved through the action of intestinal lactase (ß-galactosidase), which is located within the small intestinal brush border. This enzyme, however, is absent in neonatal monotremes and macropod marsupials. It has therefore been proposed that in these species the absorption of milk oligosaccharides is achieved by pinocytosis or endocytosis, after which digestion occurs through the actions of several lysosomal acid glycosidases. This process would enable the milk oligosaccharides of monotremes and marsupials to be utilized as a significant energy source for the suckling neonates. GENERAL SIGNIFICANCE: The evolution and significance of milk oligosaccharides is discussed in relation to the evolution of mammals.

Cortisol enhances citrulline synthesis from proline in enterocytes of suckling piglets.

There are marked decreases in plasma concentrations of cortisol and arginine (an essential amino acid for neonates) as well as intestinal citrulline synthesis in piglets during the first 14 days of life. The objective of this study was to test the hypothesis that increasing plasma cortisol concentrations by cortisol administration may prevent the decline in intestinal citrulline and arginine synthesis from proline, thereby possibly increasing plasma arginine concentration in suckling piglets and their growth. Seven-day-old pigs reared by sows received daily intramuscular injections of hydrocortisone 21-acetate (25 mg/kg) or vehicle solution (saline) (n = 10/group). At 14 days of age, piglets were used to prepare jejunal enterocytes. Cells were incubated at 37 °C for 30 min in oxygenated Krebs buffer containing 5 mM glucose, 2 mM [U-14C]proline, and 2 mM glutamine. Cortisol treatment increased plasma cortisol concentration, mitochondrial proline oxidase and N-acetylglutamate synthase activities, cytosolic argininosuccinate lyase activity, and the intracellular concentrations of N-acetylglutamate and carbamoyl phosphate for citrulline and arginine synthesis. However, cortisol treatment induced the expression of intestinal arginase-II for arginine hydrolysis, resulting in no change in plasma arginine concentration. Administration of cortisol had no effect on milk consumption or the whole-body growth rate of piglets, but increased villus height in the jejunum and ileum. Collectively, these results suggest an important role for proline oxidase and N-acetylglutamate in regulating citrulline and arginine synthesis from proline in pig enterocytes. Because proline catabolism plays an important role in modulating protein synthesis, cell proliferation, and arginine production, our findings may have important implications for understanding the role of proline oxidase in the growth and health of the mammalian small intestine.

Ascorbic acid during the suckling period is required for proper DNA demethylation in the liver.

Ascorbic acid (AA, vitamin C) serves as a cofactor for ten-eleven translocation (TET) enzymes and induces DNA demethylation in vitro. However, its role in DNA demethylation in vivo remains unclear. We previously reported that DNA demethylation in the mouse liver was enhanced during the suckling period. Therefore, we hypothesized that DNA demethylation is enhanced in an AA-dependent manner during the suckling period. To examine our hypothesis, we employed wild-type (WT) mice, which synthesize AA, and senescence marker protein-30/gluconolactonase (SMP30/GNL) knockout (KO) mice, which cannot synthesize AA, and analyzed the DNA methylation status in the livers of offspring in both the suckling period and adulthood. SMP30/GNL KO offspring showed DNA hypermethylation in the liver possibly due to low plasma and hepatic AA levels during the suckling period despite the administration of rescue-dose AA to dams. Furthermore, DNA hypermethylation of the fibroblast growth factor 21 gene (Fgf21), a PPARα target gene, persisted into adulthood. In contrast, a high-dose AA administration to SMP30/GNL KO dams during the lactation period restored DNA demethylation in the livers of offspring. Even though a slight increase was observed in plasma AA levels with the administration of rescue-dose AA to WT dams during the gestation and lactation periods, DNA demethylation in the livers of offspring was minimally enhanced. The present results demonstrate that AA intake during the suckling period is required for proper DNA demethylation in the liver.

Determinants of vitamin D status in Kenyan calves.

Vitamin D plays a critical role in calcium homeostasis and in the maintenance and development of skeletal health. Vitamin D status has increasingly been linked to non-skeletal health outcomes such as all-cause mortality, infectious diseases and reproductive outcomes in both humans and veterinary species. We have previously demonstrated a relationship between vitamin D status, assessed by the measurement of serum concentrations of the major vitamin D metabolite 25 hydroxyvitamin D (25(OH)D), and a wide range of non-skeletal health outcomes in companion and wild animals. The aims of this study were to define the host and environmental factors associated with vitamin D status in a cohort of 527 calves from Western Kenya which were part of the Infectious Disease of East African Livestock (IDEAL) cohort. A secondary aim was to explore the relationship between serum 25(OH)D concentrations measured in 7-day old calves and subsequent health outcomes over the following 12 months. A genome wide association study demonstrated that both dietary and endogenously produced vitamin D metabolites were under polygenic control in African calves. In addition, we found that neonatal vitamin D status was not predictive of the subsequent development of an infectious disease event or mortality over the 12 month follow up period.

Gestation and breastfeeding in schistosomotic mice differentially alters the expression of histone deacetylases (HDACs) in adult offspring.

BACKGROUND: Breastfeeding or gestation in schistosomotic mothers can cause long-term alterations in the immune response of offspring. OBJECTIVES: Evaluate the expression of histone deacetylases (HDACs) (all classes), the production of cytokines by T and B lymphocytes and macrophages, and the frequency of CD4+CD25+FoxP3+-cells in adult offspring born and/or suckled by schistosomotic mothers. METHODS: We harvested splenocytes from offspring born to (BIM), suckled by (SIM), or born to/suckled by (BSIM) schistosomotic mothers and animals from noninfected mothers (Control) at seven-weeks old and cultured them with/without Concanavalin A. HDAC expression was evaluated by real-time quantitative polymerase chain reaction (qPCR), and cytokines and membrane markers were evaluated by fluorescence-activated cell sorting (FACS). FINDINGS: Compared to Control, BIM mice showed increased expression of HDAC9 and frequency of CD4+IL-10+-cells. The SIM group had increased expression of HDAC1, HDAC2, HDAC6, HDAC7, HDAC10, Sirt2, Sirt5, Sirt6, and Sirt7. The BSIM group only had increased HDAC10 expression. The SIM and BSIM groups exhibited decreased frequencies of CD4+IL-4+-cells and CD4+CD25+FoxP3+-cells, along with a higher frequency of CD14+IL-10+-cells and an increase in CD45R/B220+IL-10+-cells. The BSIM group also showed a high frequency of CD4+IL10+-cells. MAIN CONCLUSIONS: Breastfeeding induced the expression of HDACs from various classes involved in reducing inflammatory responses. However, gestation enhanced the expression of a single HDAC and breastfeeding or gestation appears to favour multiple IL-10-dependent pathways, but not cells with a regulatory phenotype.

Neonatal Suckling, Oxytocin, and Early Infant Attachment to the Mother.

The neuropeptide oxytocin (OT) promotes maternal care and social affiliation in adults but its importance in infant attachment still remains unknown. True animal models of infant attachment are extremely rare, and the sheep (in complement to non-human primates) is one of the few that provides the opportunity to investigate its neuroendocrinological basis. In the lamb, access to the udder has strong rewarding properties for the establishment of a preferential relationship with the mother. Therefore, the present study explored the possible involvement of OT through its release during close social contacts with the mother. The first experiment revealed that lambs having free access to the udder from birth onward developed, by 12 h of age, a clear preference for their mothers over another maternal ewe. Delaying access to the udder for six, four or even only 2 h starting at birth, by covering the ewe's udder, resulted in the lack of such a preference without affecting general activity. These effects persisted in most cases at 24 h but by 72 h of age a bond with the mother was clearly expressed. Experiment two showed that social interactions with the mother were followed by a release of OT in the plasma when lambs had the possibility to suckle. Non-nutritive interactions were without effects. Preliminary data on two subjects suggested that OT might also increase in the cerebrospinal fluid after suckling. Finally, in the third experiment, oral administration of a non-peptide OT receptor antagonist (L-368-899, Merck) over the first 4 h after birth led to decreased exploration of the mother's body compared to lambs receiving saline, and impaired the expression of a preference for the mother at 24 h. The effects were no longer observed at 48 h. Our findings demonstrate that both delayed access to the mother's udder and OT receptor antagonist alter the onset of mother preference in newborn lambs. This suggests that central OT facilitates the development of filial attachment through its release during suckling.

Iron deficiency during pregnancy and lactation modifies the fatty acid composition of the brain of neonatal rats.

Iron deficiency is common in pregnant and lactating women and is associated with reduced cognitive development of the offspring. Since iron affects lipid metabolism, the availability of fatty acids, particularly the polyunsaturated fatty acids required for early neural development, was investigated in the offspring of female rats fed iron-deficient diets during gestation and lactation. Subsequent to the dams giving birth, one group of iron-deficient dams was recuperated by feeding an iron-replete diet. Dams and neonates were killed on postnatal days 1, 3 and 10, and the fatty acid composition of brain and stomach contents was assessed by gas chromatography. Changes in the fatty acid profile on day 3 became more pronounced on day 10 with a decrease in the proportion of saturated fatty acids and a compensatory increase in monounsaturated fatty acids. Long-chain polyunsaturated fatty acids in the n-6 family were reduced, but there was no change in the n-3 family. The fatty acid profiles of neonatal brain and stomach contents were similar, suggesting that the change in milk composition may be related to the changes in the neonatal brain. When the dams were fed an iron-sufficient diet at birth, the effects of iron deficiency on the fatty acid composition of lipids in both dam's milk and neonates' brains were reduced. This study showed an interaction between maternal iron status and fatty acid composition of the offspring's brain and suggests that these effects can be reduced by iron repletion of the dam's diet at birth.

The effects of dietary fatty acids in the physiological outcomes of maternal high-fat diet on offspring energy homeostasis in mice.

The early-life origins of disease hypothesis has been applied to obesity research and modeled through overnutrition, usually with a high-fat diet (HFD). Since the obesity epidemic coincided with societal change in dietary fat consumption, rather than amount, manipulation of fatty acid (FA) profile is an under-investigated area of study. Additionally, the binding of FAs to nuclear receptors may have persistent intergenerational, extranutritive endocrinological effects that interact with the actions of reproductive steroids causing sex-dependent effects. To determine the role of FA type in the effects underlying maternal HFD, we fed wild-type C57BL6/J mating pairs, from preconception through lactation, a HFD with high saturated fat levels from coconut oil or high linoleic acid (LA) levels from vegetable oil. Male and female offspring body weight and food intake were measured weekly for 25 weeks. Assays for glucose metabolism, body composition, and calorimetry were performed at 25 weeks. Plasma metabolic peptides and liver mRNA were measured terminally. Obesity was primarily affected by adult rather than maternal diet in males, yet in females, maternal HFD potentiated the effects of adult HFD. Maternal HFD high in LA impaired glucose disposal in males weaned onto HFD and insulin sensitivity of females. Plasma leptin correlated with adiposity, but insulin and insulin receptor expression in the liver were altered by maternal LA in males. Our results suggest that maternal FA profile is most influential on offspring glucose metabolism and that adult diet is more important than maternal diet for obesity and other parameters of metabolic syndrome.

Lipidome profiles of postnatal day 2 vaginal swabs reflect fat composition of gilt's postnatal diet.

We hypothesized that postnatal development of the vagina is impacted by early nutritional environment. Our objective was to determine if lipid profiles of vaginal swabs were different between postnatal gilts suckled by sow or fed milk replacer the first 48 h after birth, with or without a lard-based fat supplement. Gilts (>1.3 kg) were selected at birth across 8 litters and assigned to one of four treatments: 1) suckled by sow (S, n = 8); 2) suckled by sow plus administration of a fat supplement (SF, n = 5); 3) bottle-fed solely milk replacer (B, n = 8); or 4) bottle-fed solely milk replacer plus administration of a fat supplement (BF, n = 7). At 48 h postnatal, vaginal swabs of gilts were taken with a cytology brush, and lipids were extracted for analysis using multiple reaction monitoring (MRM)-profiling. Lipids extracted from serum collected at 48 h from gilts, milk collected at 24 h from sows, and milk replacer were also analyzed with MRM-profiling. Receiver operating characteristic curve analysis found 18 lipids recovered from vaginal swabs that highly distinguished between S and B gilts [area-under-the-curve (AUC) > 0.9], including phosphatidylethanolamine with 34 carbons and four unsaturations in the fatty acyl residues [PE (34:4)]. Twelve lipids from vaginal swabs highly correlated (r > 0.6; p < 0.01) with nutrition source. Lipids with greater abundance in milk replacer drove association. For example, mean intensity of PE (34:4) was 149-fold higher in milk replacer than colostrum. Consequently, PE (34:4) was found to have 1.6- and 2.12-fold higher levels in serum and vaginal swab samples (p < 0.001), respectively, of B gilts as compared to S gilts. Findings support that vaginal swabs can be used to noninvasively study effects of perinatal nutrition on tissue composition.

Effects of maternal alpha-ketoglutarate supplementation during lactation on the performance of lactating sows and suckling piglets.

The aim of the study was to investigate if dietary alpha-ketoglutarate (AKG) supplementation may improve the performance of lactating sows and their suckling piglets. After farrowing, 24 lactating sows (Large White × Landrace) with similar body weight (BW) were assigned to the control and AKG groups based on parity, and their lactation diets were supplemented with 0.00 or 0.25% AKG, respectively. It was found that supplementing the diet of lactating sows with 0.25% AKG enhanced growth performance of the suckling piglets from d 7 to d 21 of the lactation period, improved villus height of ileum and tended (p = 0.085) to increase mean volumetric bone mineral density of femur in the weanling piglets. In the lactating sows, dietary supplementation of AKG decreased plasma urea level on d 14 of lactation, decreased plasma calcium (Ca) concentrations from d 7 to d 21 of lactation and increased lactose and Ca levels in ordinary milk. Thus, it was proposed that AKG supplementation stimulates the capacity for lactose synthesis and Ca uptake in the mammary gland, thereby altering the composition of the ordinary milk which might be associated with the enhanced performance of piglets during the suckling period. These findings could lead to a better application of AKG in lactating nutrition, and therefore, promoting pork production.

Effect of the maternal feeding on the carotenoid and tocopherol content of suckling lamb tissues.

The objectives of the present study were to quantify the deposition of carotenoids and tocopherols in the tissues of suckling lamb and to use the levels of those compounds to trace the maternal feeding. Twenty suckling lambs were raised with their dams in vegetative-stage pastures, and 19 suckling lambs were stalled indoors with dams that received hay ad libitum, until the lambs reached 10-12 kg. The lambs' weekly intake of carotenoids and tocopherols was estimated from the milk production of the ewes and the carotenoid and tocopherol content of the milk. Samples of the subcutaneous and perirenal fat, longissimus thoracis muscle, and liver of the suckling lambs were collected at 24 h after slaughter. The pasture-raised lambs had greater intake of lutein than their indoor counterparts throughout the suckling period (p < 0.05), more retinol during the second and third weeks of the suckling period (p < 0.05), and more α-tocopherol during the first three weeks of the suckling period (p < 0.05), being similar thereafter. The pasture-raised lambs, when compared to the lambs raised indoors, had greater lutein content in the muscle and liver (p < 0.001), retinol and α-tocopherol content in all tissues (p < 0.001) and muscle and liver γ-tocopherol content (p < 0.05). The maternal feeding could be accurately predicted from the carotenoid and tocopherol content of whole lamb carcasses and muscle tissue but not from those of ewes' milk, lamb liver tissue or lamb fat deposits.

Effects of dietary resveratrol supplementation during gestation and lactation of sows on milk composition of sows and fat metabolism of sucking piglets.

The purpose of this article was to investigate the effects of dietary resveratrol supplementation during gestation and lactation of sows on the milk composition of sows and the fat metabolism of sucking piglets. Forty sows were allotted to two experimental treatment groups that included the following: (a) control sows (CON treatment, n = 20) fed with a corn-soybean meal control diet and (b) treatment sows (RES treatment, n = 20) fed with a control diet with addition of 300 mg/kg resveratrol. The results showed that the content of lactose in the colostrum was increased (p < 0.05) and the content of fat in 21-day milk was increased (p < 0.05) by dietary resveratrol supplementation. In the RES treatment group, the concentrations of high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), lipase activity and insulin (INS) in plasma of sucking piglets were increased (p < 0.05). In the adipose tissue, the enzyme activities of hormone-sensitive lipase (HSL), acetyl-CoA carboxylase (ACC) and lipoprotein lipase (LPL) increased significantly by RES treatment (p < 0.05), and the mRNA levels of acetyl coenzyme A-alpha (ACCα), LPL, fatty acid transport protein (FATP1) and CCAAT-enhancer-binding protein gene (C/EBPα) were higher in the RES treatment group (p < 0.05). In conclusion, resveratrol supplementation on gestational and lactating sows improved the content of lactose in the colostrum and the content of fat in milk at day 21 of lactation. In addition, resveratrol supplementation on sows increased HDL and LDL in the plasma of piglets. In piglet adipose tissue, the enzyme activity and mRNA level related to lipolysis, fatty acid uptake from circulating triacylglycerols and lipogenesis are partially improved by resveratrol supplementation on sows. These aspects affect fat metabolism in piglets.

Dietary iron absorption during early postnatal life.

Inadequate iron levels during early life can have adverse consequences for the developing infant. Iron deficiency during this critical period of growth can affect brain development and cognitive function, problems that can be lifelong despite subsequent correction of the iron deficit. Therefore, it is critical that the suckling infant has sufficient iron for their developmental needs. Much of the iron used in the immediate post-natal period is stored iron that was acquired from the mother in the final trimester of pregnancy, however, despite having low iron levels, breast milk can also make a significant contribution to infant iron needs. This reflects the ability of the suckling infant to absorb dietary iron far more efficiently than is possible after weaning. The mechanisms underlying this enhanced iron absorption are poorly understood. The iron export protein ferroportin is essential for this process, as it is in adults, however, the role of other molecules normally involved in iron absorption following weaning is less clear. The composition and distribution of iron in breast milk may be important, as could the contribution of more distal parts of the gastrointestinal tract. This review discusses the potential role of each of the above components in intestinal iron absorption during suckling and highlights the need for further research into this important process.

Transfer of amoxicillin to suckling mink (Neovison vison) kits via the milk from dams treated orally or intra-muscularly.

Treatment of mink kits with pre-weaning diarrhea (PWD) can be time-consuming and expensive for the farmer, and the efficacy of the treatment procedure may be questioned. Evidence-based treatment protocols for application on affected animals at farms with outbreaks of PWD are lacking. In Denmark, the dams are sometimes treated with amoxicillin, however, it is unknown if it is passed on to the mink kits via the milk. The aim of the present study was to investigate if amoxicillin is transferred via the milk to the kits after oral (PO) and intramuscular (IM) treatment, respectively, of the dam. Moreover, we estimated the concentrations of amoxicillin continuously in serum from the kits up to 8 h after administration. The concentration of amoxicillin was not affected by the route of administration (P = .64) and serum reached the highest level after 8 h (34 ng/mL, CI95% = [24.3-47.7]). The serum concentrations of amoxicillin in the mink kits achieved within 8 h were judged too low to exert antimicrobial impact on relevant bacterial species.

Gestation and breastfeeding in schistosomotic mice differentially alters the expression of histone deacetylases (HDACs) in adult offspring

BACKGROUND Breastfeeding or gestation in schistosomotic mothers can cause long-term alterations in the immune response of offspring. OBJECTIVES Evaluate the expression of histone deacetylases (HDACs) (all classes), the production of cytokines by T and B lymphocytes and macrophages, and the frequency of CD4+CD25+FoxP3+-cells in adult offspring born and/or suckled by schistosomotic mothers. METHODS We harvested splenocytes from offspring born to (BIM), suckled by (SIM), or born to/suckled by (BSIM) schistosomotic mothers and animals from noninfected mothers (Control) at seven-weeks old and cultured them with/without Concanavalin A. HDAC expression was evaluated by real-time quantitative polymerase chain reaction (qPCR), and cytokines and membrane markers were evaluated by fluorescence-activated cell sorting (FACS). FINDINGS Compared to Control, BIM mice showed increased expression of HDAC9 and frequency of CD4+IL-10+-cells. The SIM group had increased expression of HDAC1, HDAC2, HDAC6, HDAC7, HDAC10, Sirt2, Sirt5, Sirt6, and Sirt7. The BSIM group only had increased HDAC10 expression. The SIM and BSIM groups exhibited decreased frequencies of CD4+IL-4+-cells and CD4+CD25+FoxP3+-cells, along with a higher frequency of CD14+IL-10+-cells and an increase in CD45R/B220+IL-10+-cells. The BSIM group also showed a high frequency of CD4+IL10+-cells. MAIN CONCLUSIONS Breastfeeding induced the expression of HDACs from various classes involved in reducing inflammatory responses. However, gestation enhanced the expression of a single HDAC and breastfeeding or gestation appears to favour multiple IL-10-dependent pathways, but not cells with a regulatory phenotype.

Grape pomace in ewes diet: Effects on meat quality and the fatty acid profile of their suckling lambs.

Grape pomace (GP) is an inexpensive natural antioxidant promising as animal feed supplement due to its high content of phenolic compounds. In order to evaluate its effect in lactating ewe rations on meat quality and fat composition of their suckling lambs, 48 Churra ewes were divided into 4 treatments. All animals were fed a ration containing linseed oil (Control) supplemented with Vitamin E or two levels of GP. Lambs were nourished exclusively by suckling until they were slaughtered. Dietary GP did not generate adverse effects on carcasses or lambs meat quality when compared with Control or Vit-E diets. GP improved the water holding capacity of the meat. In addition, lambs meat FA profile was not nutritionally affected with the diets assayed. Hence, the use of GP as a dietary supplement in ewe rations would not have negative effects on meat from suckling lambs.

Effects of butyrate supplementation in antibiotic-free milk replacer and starter on growth performance in suckling calves.

The aim of this study was to evaluate butyrate supplementation of antibiotic-free milk replacer and starter on growth performance in male Holstein calves. Twenty-nine calves were divided into two groups. Group C (n = 13) was fed antibiotic-free milk replacer without supplementation, and Group B (n = 16) was fed antibiotic-free milk replacer supplemented with butyrate (1.6 % DM of Gustor BP70® ). Starter in Group B contained 0.3 % DM of Gustor BP70® . The intake of milk replacer was lower in group B than in C (p = 0.07 for the treatment x week interaction). Body weight (BW) and heart girth (HG) in group B was higher than in C during the experimental period (p = 0.07 and 0.01 for the treatment × week interaction, respectively). The duration of the weaning period in group B was shorter than in group C (p = 0.02). ß-hydroxybutyrate (BHBA) was higher in group B than in C (p = 0.04). Insulin like growth factor-1 (IGF-1) concentrations tended to be higher in group B than in C (p = 0.07 for treatment × week interaction). Our results show that butyrate supplementation in antibiotic-free milk replacer and starter exerted positive effects on growth performance in suckling calves.

Effect of Maternal Administration of Edible Bird's Nest on the Learning and Memory Abilities of Suckling Offspring in Mice.

Although human brains continue developing throughout the underage developmental stages, the infancy period is considered the most important one for the whole life. It has been reported that sialic acid from edible bird's nest (EBN) can facilitate the development of brain and intelligence. In this study, by oral administration of EBN to female mice during the pregnancy or lactation period, the effects of EBN on the levels of sialic acid in mouse milk were determined using high-performance liquid chromatography (HPLC). Furthermore, the spatial learning performances of their offspring were assessed using the Morris water maze test. Additionally, cerebral malondialdehyde (MDA), superoxide dismutase (SOD), choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) in cubs nursed by the female mice given the EBN homogenate were examined, while BDNF immunohistochemical staining and neuron count in hippocampi were investigated as well. These results showed that administration with EBN in maternal mice during pregnancy or lactation period can improve the learning and memory functions in their offspring, possibly by increasing the activities of SOD and ChAT and, at the meantime, decreasing the levels of MDA and activities of AChE. Moreover, BDNF levels for CA1, CA2, and CA3 regions in hippocampi and the numbers of dyed neurons in CA1, CA2, CA3, and DG regions among the offspring were significantly enhanced due to the intake of EBN by the maternal mice. We concluded that maternal administration of EBN during the pregnancy and lactation periods can improve the spatial learning performances in the offspring.

N-acetylcysteine attenuates intrauterine growth retardation-induced hepatic damage in suckling piglets by improving glutathione synthesis and cellular homeostasis.

PURPOSE: The objective of the present study was to test the hypothesis that N-acetylcysteine (NAC) may play beneficial roles against intrauterine growth retardation (IUGR)-induced hepatic damage in suckling piglets. METHODS: Fourteen IUGR and seven normal birth weight (NBW) neonatal male piglets were selected. Piglets were weaned at 7 days of postnatal age and fed the control formula milk (NBW-CON and IUGR-CON groups) or the control formula milk supplemented with 1.2 g/kg NAC (IUGR-NAC group) for 14 days (n = 7). The plasma and liver samples were analyzed for the parameters related to hepatic damage, redox status, apoptosis, and autophagy. RESULTS: Compared with the NBW-CON group, IUGR-CON group exhibited increased activities of plasma aminotransferases, increased numbers of apoptotic hepatocytes, as well as higher concentrations of protein carbonyl, malondialdehyde (MDA), microtubule-associated protein 1 light chain 3 beta, and phospholipid-conjugated form (MAP1LC3B-II), along with a decrease in the content of reduced glutathione (GSH). NAC treatment increased GSH content and GSH-to-oxidized GSH ratio in the liver of IUGR-NAC group, most likely owing to the improved activities of γ-glutamine-cysteine ligase, γ-glutamine-cysteine synthetase, and glutathione reductase. The hepatic protein carbonyl and MDA contents were decreased in the IUGR-NAC group compared with the IUGR-CON group. In addition, NAC-treated piglets had an increased content of B cell lymphoma/leukemia 2 protein, whereas a decreased expression level of MAP1LC3B-II in the liver. CONCLUSIONS: NAC may have beneficial effects in improving GSH synthesis and cellular homeostasis in the liver of IUGR suckling piglets.

Formula diet driven microbiota shifts tryptophan metabolism from serotonin to tryptamine in neonatal porcine colon.

BACKGROUND: The gut microbiota of breast-fed and formula-fed infants differ significantly, as do the risks for allergies, gut dysfunction, and upper respiratory tract infections. The connections between breast milk, various formulas, and the profiles of gut bacteria to these childhood illnesses, as well as the mechanisms underlying the effects, are not well understood. METHODS: We investigated distal colon microbiota by 16S RNA amplicon sequencing, morphology by histomorphometry, immune response by cytokine expression, and tryptophan metabolism in a pig model in which piglets were sow-fed, or fed soy or dairy milk-based formula from postnatal day (PND) 2 to 21. RESULTS: Formula feeding significantly (p < 0.05) altered the colon microbiota relative to the sow feeding. A significant reduction in microbial diversity was noted with formula groups in comparison to sow-fed. Streptococcus, Blautia, Citrobacter, Butrycimonas, Parabacteroides, Lactococcus genera were increased with formula feeding relative to sow feeding. In addition, relative to sow feeding, Anaerotruncus, Akkermansia, Enterococcus, Acinetobacter, Christensenella, and Holdemania were increased in milk-fed piglets, and Biliophila, Ruminococcus, Clostridium were increased in soy-fed piglets. No significant gut morphological changes were noted. However, higher cytokine mRNA expression (BMP4, CCL11, CCL21) was observed in the distal colon of formula groups. Formula feeding reduced enterochromaffin cell number and serotonin, but increased tryptamine levels relative to sow feeding. CONCLUSION: Our data confirm that formula diet alters the colon microbiota and appears to shift tryptophan metabolism from serotonin to tryptamine, which may lead to greater histamine levels and risk of allergies in infants.