Metabolite profiling of peripheral blood plasma in pigs in early postnatal life fed whole bovine, caprine or ovine milk

Ruminants’ milk is commonly used for supplying nutrients to infants when breast milk is unavailable or limited. Previous studies have highlighted the differences between ruminants’ milk composition, digestion, absorption, and fermentation. However, whether consuming different ruminants’ milk impact the appearance of the circulatory blood metabolites in the early postnatal life is not well understood. The analysis conducted here aimed to determine the effect of feeding exclusively whole milk from bovine, caprine or ovine species to pigs, approximately 7 days-old for 15 days, on circulatory blood plasma metabolites. Relative intensities of plasma metabolites were detected using a liquid chromatography-mass spectrometry based metabolomic approach. Seven polar and 83 non-polar (lipids) metabolites in plasma were significantly different (false discovery rate < 0.05) between milk treatments. These included polar metabolites involved in amino acid metabolism and lipids belonging to phosphatidylcholine, lysophosphatidylcholine, sphingomyelin, and triglycerides. Compared to the caprine or bovine milk group, the relative intensities of polar metabolites and unsaturated triglycerides were higher in the peripheral circulation of the ovine milk group. In contrast, relative intensities of saturated triglycerides and phosphatidylcholine were higher in the bovine milk group compared to the ovine or caprine milk group. In addition, correlations were identified between amino acid and lipid intake and their appearance in peripheral blood circulation. The results highlighted that consuming different ruminants’ milk influences the plasma appearance of metabolites, especially lipids, that may contribute to early postnatal life development in pigs

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Dietary Iron Repletion following Early-Life Dietary Iron Deficiency Does Not Correct Regional Volumetric or Diffusion Tensor Changes in the Developing Pig Brain

BackgroundIron deficiency is the most common micronutrient deficiency worldwide and children are at an increased risk due to the rapid growth occurring during early life. The developing brain is highly dynamic, requires iron for proper function, and is thus vulnerable to inadequate iron supplies. Iron deficiency early in life results in altered myelination, neurotransmitter synthesis, neuron morphology, and later-life cognitive function. However, it remains unclear if dietary iron repletion after a period of iron deficiency can recover structural deficits in the brain.MethodTwenty-eight male pigs were provided either a control diet (CONT; n = 14; 23.5 mg Fe/L milk replacer) or an iron-deficient diet (ID; n = 14; 1.56 mg Fe/L milk replacer) for phase 1 of the study, from postnatal day (PND) 2 until 32. Twenty pigs (n = 10/diet from phase 1) were used in phase 2 of the study from PND 33 to 61, all pigs were provided a common iron sufficient diet, regardless of their early-life dietary iron status. All pigs remaining in the study were subjected to magnetic resonance imaging (MRI) at PND 32 and again at PND 61 using structural imaging sequences and diffusion tensor imaging (DTI) to assess volumetric and microstructural brain development, respectively. Data were analyzed using a two-way ANOVA to assess the main and interactive effects of early-life iron status and time.ResultsAn interactive effect was observed for absolute whole brain volumes, in which whole brain volumes of ID pigs were smaller at PND 32 but were not different than CONT pigs at PND 61. Analysis of brain region volumes relative to total brain volume indicated interactive effects (i.e., diet × day) in the cerebellum, olfactory bulb, and putamen-globus pallidus. Main effects of early-life iron status, regardless of imaging time point, were noted for decreased relative volumes of the left hippocampus, right hippocampus, thalamus, and increased relative white matter volume in ID pigs compared with CONT pigs. DTI indicated interactive effects for fractional anisotropy (FA) in the whole brain, left cortex, and right cortex. Main effects of early-life iron status, regardless of imaging time point, were observed for decreased FA values in the caudate, cerebellum, and internal capsule in ID pigs compared with CONT pigs. All comparisons described above were significant at P < 0.05.ConclusionResults from this study indicate that dietary iron repletion is able to compensate for reduced absolute brain volumes early in life; however, microstructural changes and altered relative brain volumes persist despite iron repletion

Dietary alpha-Lipoic Acid Alters Piglet Neurodevelopment

Introduction: Alpha-lipoic acid (a-LA) is an antioxidant shown to ameliorate age-associated impairments of brain and cardiovascular function. Human milk is known to have high antioxidant capacity, however the role of antioxidants in the developing brain is largely uncharacterized. This exploratory study aimed to examine the dose response effects of a-LA on piglet growth and neurodevelopment. Methods: Beginning at 2 d of age, 31 male pigs received one of three diets: control (CONT) [0 mg a-LA/100g], low a-LA (LOW) [120 mg a-LA/100g], or high a-LA (HIGH) [240 mg a-LA/100g]. From 14 to 28 d of age, pigs were subjected to spatial T-maze assessment and macrostructural and microstructural neuroimaging procedures were performed at 31 d of age.Results: No differences due to diet were observed for bodyweight gain or intestinal weight and length. Spatial T-maze assessment did not reveal learning differences due to diet in proportion of correct choices or latency to choice measures. Diffusion tensor imaging revealed decreased (P = 0.01) fractional anisotropy (FA) in the internal capsule of HIGH fed pigs compared with both the CONT (P < 0.01) and LOW (P = 0.03) fed pigs, which were not different from one another. Analysis of axial diffusivity (AD) within the internal capsule revealed a main effect of diet (P < 0.01) in which HIGH fed piglets exhibited smaller (P < 0.01) rates of diffusion compared with CONT piglets, but HIGH fed piglets were not different (P = 0.12) than LOW fed piglets. Tract-based spatial statistics, a comparison of FA values along white matter tracts, revealed 1,650 voxels where CONT piglets exhibited higher (P < 0.05) values compared with HIGH fed piglets. Conclusion: The lack of differences in intestinal and bodyweight measures among piglets indicate a-LA supplementation does not impact overall growth, regardless of concentration. Additionally, no observed differences between CONT and LOW fed piglets in behavior and neuroimaging measures indicate a low concentration of a-LA does not affect normal brain development. Supplementation of a-LA at a high concentration appeared to alter white matter maturation in the internal capsule, which may indicate delayed neurodevelopment in these piglets

Longitudinal Effects of Iron Deficiency Anemia and Subsequent Repletion on Blood Parameters and the Rate and Composition of Growth in Pigs

Iron deficiency is reported as the most common nutrient deficiency worldwide. Due to rapid growth, infants are at particular risk for developing iron deficiency, which can easily progress to iron deficiency anemia (IDA), if not treated. The aim of this study was to determine the lasting effects of an early-life iron deficiency after a period of dietary iron repletion. Forty-two intact male pigs were fed, ad libitum, either control (CONT, 21.3 mg Fe/L) or iron-deficient (ID 2.72 mg Fe/L) milk replacer from postnatal day (PND) 2 to 32 (phase 1). From PND 33 to 61 (phase 2), all pigs were transitioned onto a series of industry-standard, iron-adequate diets. Blood was collected weekly from PND 7 to 28, and again on PND 35 and 56, and tissues were collected at either PND 32 or PND 61. At the end of phase 1, ID pigs exhibited reduced hematocrit (Hct; p &lt; 0.0001) and hemoglobin (Hb; p &lt; 0.0001) compared with CONT pigs, but neither Hct (p = 0.5968) nor Hb (p = 0.6291) differed between treatment groups after dietary iron repletion at the end of phase 2. Body weight gain was reduced (p &lt; 0.0001) 58% at PND 32 in ID pigs compared with CONT pigs during phase 1, and this effect remained significant at the end of phase 2 (p = 0.0001), with ID pigs weighing 34% less than CONT pigs at PND 61. Analysis of peripheral protein and messenger RNA (mRNA) gene expression biomarkers yielded inconclusive results, as would be expected based on previous biomarker analyses across multiple species. These findings suggest that early-life iron status negatively influences blood parameters and growth performance, with dietary iron repletion allowing for full recovery of hematological outcomes, but not growth performance

Comparison of brain development in sow-reared and artificially-reared piglets

IntroductionProvision of adequate nutrients is critical for proper growth and development of the neonate, yet the impact of breastfeeding versus formula feeding on neural maturation has yet to be fully determined. Using the piglet as a model for the human infant, our objective was to compare neurodevelopment of piglets that were either sow-reared or reared in an artificial setting. MethodsOver a 25-d feeding study, piglets (1.5 ± 0.2 kg initial bodyweight) were either sow-reared (SR; n = 10) with ad libitum intake, or artificially-reared (AR; n = 29) receiving an infant formula modified to mimic the nutritional profile and intake pattern of sow’s milk. At study conclusion, piglets were subjected to a standardized set of magnetic resonance imaging (MRI) procedures to quantify structure and composition of the brain.ResultsDiffusion tensor imaging, an MRI sequence that characterizes brain microstructure, revealed that SR piglets had greater (P < 0.05) average whole-brain fractional anisotropy, and lower (P < 0.05) mean and radial and axial diffusivity values compared with AR piglets, suggesting differences in white matter organization. Voxel-based morphometric analysis, a measure of white and gray matter volumes concentrations, revealed differences (P < 0.05) in bilateral development of gray matter clusters in the cortical brain regions of the AR piglets compared with SR piglets. Region of interest (ROI) analysis revealed larger (P < 0.05) whole brain volumes in SR animals compared with AR, and subcortical regions to be larger (P < 0.05) as a percentage of whole-brain volume in AR piglets compared with SR animals. Quantification of brain metabolites using magnetic resonance spectroscopy revealed SR piglets had higher (P < 0.05) concentrations of myo-inositol, glycerophosphocholine + phosphocholine, and creatine + phosphocreatine compared with AR piglets. However, glutamate + glutamine levels were higher (P < 0.05) in AR piglets when compared with SR animals. ConclusionOverall, increases in brain metabolite concentrations, coupled with greater FA values in white matter tracts and volume differences in gray matter of specific brain regions, suggest differences in myelin development and cell proliferation in SR vs. AR piglets

Moderate Perinatal Choline Deficiency Elicits Altered Physiology and Metabolomic Profiles in the Piglet

<div><p>Few studies have evaluated the impact of dietary choline on the health and well-being of swine, and those pivotal papers were aimed at determining dietary requirements for sows and growing pigs. This is of importance as the piglet is becoming a widely accepted model for human infant nutrition, but little is known about the impacts of perinatal choline status on overall health and metabolism of the growing piglet. In the present study, sows were provided either a choline deficient (CD, 625 mg choline/kg dry matter) or choline sufficient (CS, 1306 mg choline/kg dry matter) diet for the last 65 d of gestation (prenatal intervention). Piglets were weaned from the sow 48 h after farrowing and provided either a CD (477 mg choline/kg dry matter) or CS (1528 mg choline/kg dry matter) milk replacer (postnatal intervention) for 29 ± 2 d, resulting in a factorial arrangement of 4 treatment (prenatal/postnatal) groups: CS/CS, CS/CD, CD/CS, and CD/CD. Piglet growth was normal for artificially-reared piglets, and was not impacted by perinatal choline status. Piglets receiving the postnatal CD treatment had lower (<i>P</i> < 0.01) plasma choline and choline-containing phospholipid concentrations and higher (<i>P</i> < 0.05) liver enzyme (alkaline phosphatase and gamma-glutamyl transferase) values compared with piglets receiving the postnatal CS treatment. Hepatic lipid content of piglets receiving the postnatal CD treatment was higher (<i>P</i> < 0.01) compared with piglets receiving the postnatal CS treatment. Additionally, postnatally CD piglets had lower (<i>P</i> = 0.01) plasma cholesterol than postnatally CS piglets. Brain development was also impacted by perinatal choline status, with brains of piglets exposed to prenatal CD being smaller (<i>P</i> = 0.01) than those of prenatally CS piglets. These findings support the hypothesis that the piglet is a sensitive model for choline deficiency during the perinatal period. In the present study, piglets exhibited similarities in health markers and metabolomic profiles to rodents and humans when exposed to moderate choline deficiency.</p></div