{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:06:32Z","timestamp":1791875192490,"version":"4.3.4"},"reference-count":99,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T00:00:00Z","timestamp":1651017600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["ME 1420\/10-1"],"award-info":[{"award-number":["ME 1420\/10-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["ZE 322\/4-1"],"award-info":[{"award-number":["ZE 322\/4-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      It has been shown that small intestine development in low birth weight\n                      <jats:bold>(LBW)<\/jats:bold>\n                      piglets is impaired. Glutamine\n                      <jats:bold>(Gln)<\/jats:bold>\n                      has been reported to improve piglet health and intestinal function in weaned piglets, but data is scarce in suckling piglets. This study was conducted to investigate the effects of oral Gln supplementation compared to Alanine (\n                      <jats:bold>Ala<\/jats:bold>\n                      ) on jejunal development and function in 5 and 12 d old male LBW and normal birth weight\n                      <jats:bold>(NBW)<\/jats:bold>\n                      suckling piglets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Gln had no effect on the jejunal morphology, development, tissue and digesta amino acid profiles and mRNA abundance of genes involved in amino acid transport, metabolism, glutathione synthesis in LBW piglets when compared to Ala supplementation and birth weight controls at 5 and 12 d. Only the concentration of Gln in jejunal tissue was higher in NBW piglets supplemented with Gln compared to Ala at 5 d (P &lt; 0.05). A comparison of the birth weight groups showed no differences between LBW and NBW piglets at 5 and 12 d in any parameter. Jejunal crypt depth, villus height \/ width, tunica muscularis thickness, number of goblet and IgA positive cells, the ratio of jejunal RNA to DNA and the concentration of DNA, protein and RNA changed (P &lt; 0.05) from 5 compared to 12 d. The concentrations of several free, and protein bound amino acids as well as amino metabolites differed between age groups in jejunal tissue but the digesta concentrations were affected to a lesser extent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Oral Gln supplementation to suckling male piglets over the first 12 d of life was not associated with changes in jejunal parameters measured in this study. The absence of effects may indicate that Gln is absorbed as well as metabolized in the upper intestinal tract and thus could benefit intestinal development at a more proximal location.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0267357","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T13:32:47Z","timestamp":1651066367000},"page":"e0267357","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Effects of oral glutamine supplementation on jejunal morphology, development, and amino acid profiles in male low birth weight suckling piglets"],"prefix":"10.1371","volume":"17","author":[{"given":"Johannes","family":"Schregel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8675-9258","authenticated-orcid":true,"given":"Johannes","family":"Schulze Holthausen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriama","family":"Sciascia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solvig","family":"G\u00f6rs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Eggert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armin","family":"Tuchscherer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Zentek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9498-6020","authenticated-orcid":true,"given":"Cornelia C.","family":"Metges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,4,27]]},"reference":[{"issue":"2","key":"pone.0267357.ref001","article-title":"Using Nutritional Strategies to Shape the Gastro-Intestinal Tracts of Suckling and Weaned Piglets.","volume":"11","author":"AMS Huting","year":"2021","journal-title":"Animals (Basel)."},{"issue":"2","key":"pone.0267357.ref002","article-title":"Alterations in the liver of intrauterine growth retarded piglets may predispose to development of insulin resistance and obesity in later life","volume":"69","author":"K Ferenc","year":"2018","journal-title":"Journal of physiology and pharmacology: an official journal of the Polish Physiological Society"},{"key":"pone.0267357.ref003","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.livsci.2010.06.015","article-title":"Intrauterine growth restriction reduces intestinal structure and modifies the response to colostrum in preterm and term piglets","volume":"133","author":"R D\u2019Inca","year":"2010","journal-title":"Livestock science"},{"issue":"10","key":"pone.0267357.ref004","doi-asserted-by":"crossref","first-page":"4991","DOI":"10.2527\/jas.2012-5740","article-title":"Individual physical characteristics of neonatal piglets affect preweaning survival of piglets born in a noncrated system","volume":"91","author":"J Hales","year":"2013","journal-title":"Journal of animal science"},{"key":"pone.0267357.ref005","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0030318","article-title":"The Weaker Sex? The Propensity for Male-Biased Piglet Mortality.","volume":"7","author":"E Baxter","year":"2012","journal-title":"Plos One."},{"key":"pone.0267357.ref006","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1136\/vr.147.8.209","article-title":"Timing and causes of piglet mortality in alternative and conventional farrowing systems","volume":"147","author":"J Marchant","year":"2000","journal-title":"The Veterinary record"},{"issue":"8","key":"pone.0267357.ref007","doi-asserted-by":"crossref","first-page":"2767","DOI":"10.2527\/jas.2009-2222","article-title":"Impact of piglet birth weight, birth order, and litter size on subsequent growth performance, carcass quality, muscle composition, and eating quality of pork","volume":"88","author":"AD Beaulieu","year":"2010","journal-title":"Journal of animal science"},{"key":"pone.0267357.ref008","doi-asserted-by":"crossref","first-page":"441","DOI":"10.2527\/jas.2015-9788","article-title":"REVIEW: The pig as a model for humans: Effects of nutritional factors on intestinal function and health","volume":"94","author":"M Sciascia","year":"2016","journal-title":"Journal of animal science"},{"key":"pone.0267357.ref009","doi-asserted-by":"crossref","first-page":"67","DOI":"10.4137\/CMPed.S40070","article-title":"Intrauterine Growth Restriction: Antenatal and Postnatal Aspects.","volume":"10","author":"D Sharma","year":"2016","journal-title":"Clinical medicine insights Pediatrics"},{"issue":"1","key":"pone.0267357.ref010","doi-asserted-by":"crossref","first-page":"112","DOI":"10.2527\/2006.841112x","article-title":"Developmental changes in morphometry of the small intestine and jejunal sucrase activity during the first nine weeks of postnatal growth in pigs","volume":"84","author":"O Adeola","year":"2006","journal-title":"Journal of animal science"},{"issue":"5","key":"pone.0267357.ref011","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1203\/00006450-199505000-00006","article-title":"Nutrient-independent and nutrient-dependent factors stimulate protein synthesis in colostrum-fed newborn pigs","volume":"37","author":"DG Burrin","year":"1995","journal-title":"Pediatric research"},{"issue":"4","key":"pone.0267357.ref012","doi-asserted-by":"crossref","first-page":"186","DOI":"10.54846\/jshap\/875","article-title":"Influence of age at weaning and feeding regimes on the postnatal morphology of the porcine small intestine","volume":"23","author":"S Al Masri","year":"2015","journal-title":"Journal of Swine Health and Production"},{"key":"pone.0267357.ref013","doi-asserted-by":"crossref","first-page":"3","DOI":"10.22358\/jafs\/66152\/2011","article-title":"The development of the small intestine of piglets\u2014Chosen aspects","volume":"20","author":"M Barszcz","year":"2011","journal-title":"Journal of animal and feed sciences"},{"key":"pone.0267357.ref014","doi-asserted-by":"crossref","DOI":"10.1186\/s40104-016-0063-2","article-title":"Developmental changes in intercellular junctions and Kv channels in the intestine of piglets during the suckling and post-weaning periods","volume":"7","author":"J Wang","year":"2016","journal-title":"Journal of animal science and biotechnology"},{"key":"pone.0267357.ref015","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.anifeedsci.2017.06.011","article-title":"A review on early gut maturation and colonization in pigs, including biological and dietary factors affecting gut homeostasis","volume":"233","author":"N Everaert","year":"2017","journal-title":"Animal feed science and technology"},{"issue":"5","key":"pone.0267357.ref016","article-title":"MicroRNA-29a mediates the impairment of intestinal epithelial integrity induced by intrauterine growth restriction in pig","volume":"312","author":"Y Zhu","year":"2017","journal-title":"American journal of physiology Gastrointestinal and liver physiology"},{"issue":"7","key":"pone.0267357.ref017","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1017\/S0007114518000375","article-title":"Innate differences and colostrum-induced alterations of jejunal mucosal proteins in piglets with intra-uterine growth restriction","volume":"119","author":"X Wang","year":"2018","journal-title":"The British journal of nutrition"},{"key":"pone.0267357.ref018","doi-asserted-by":"crossref","first-page":"5238134","DOI":"10.1155\/2017\/5238134","article-title":"Structure and Function of Enterocyte in Intrauterine Growth Retarded Pig Neonates","volume":"2017","author":"K Ferenc","year":"2017","journal-title":"Disease markers"},{"key":"pone.0267357.ref019","article-title":"Artificial rearing of piglets: effects on small intestinal morphology and digestion capacity.","author":"M De Vos","year":"2014","journal-title":"Livestock science"},{"issue":"2","key":"pone.0267357.ref020","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.clnu.2013.05.013","article-title":"Bovine colostrum improves intestinal function following formula-induced gut inflammation in preterm pigs","volume":"33","author":"AC St\u00f8y","year":"2014","journal-title":"Clinical nutrition: official journal of the European Society of Parenteral and Enteral Nutrition"},{"issue":"3","key":"pone.0267357.ref021","doi-asserted-by":"crossref","first-page":"989","DOI":"10.2527\/jas.2015-9942","article-title":"Bovine milk-based formula leads to early maturation-like morphological, immunological, and functional changes in the jejunum of neonatal piglets","volume":"94","author":"R Pieper","year":"2016","journal-title":"Journal of animal science"},{"issue":"6","key":"pone.0267357.ref022","article-title":"Dietary Nucleotides Supplementation Improves the Intestinal Development and Immune Function of Neonates with Intra-Uterine Growth Restriction in a Pig Model.","volume":"11","author":"L Che","year":"2016","journal-title":"Plos One"},{"issue":"1","key":"pone.0267357.ref023","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s40104-021-00581-3","article-title":"Short-chain fatty acids can improve lipid and glucose metabolism independently of the pig gut microbiota","volume":"12","author":"H Zhou","year":"2021","journal-title":"Journal of animal science and biotechnology"},{"issue":"12","key":"pone.0267357.ref024","doi-asserted-by":"crossref","first-page":"5754","DOI":"10.2527\/jas.2015-9293","article-title":"Plasma metabolomics indicates metabolic perturbations in low birth weight piglets supplemented with arginine","volume":"93","author":"CM Getty","year":"2015","journal-title":"Journal of animal science"},{"issue":"3","key":"pone.0267357.ref025","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1093\/jn\/124.3.415","article-title":"Free and protein-bound amino acids in sow\u2019s colostrum and milk","volume":"124","author":"G Wu","year":"1994","journal-title":"The Journal of nutrition"},{"issue":"2","key":"pone.0267357.ref026","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1203\/00006450-199408000-00007","article-title":"Glucose, galactose, and glutamine metabolism in pig isolated enterocytes during development","volume":"36","author":"B Darcy-Vrillon","year":"1994","journal-title":"Pediatric research"},{"key":"pone.0267357.ref027","article-title":"Glutamine and glucose metabolism in enterocytes of the neonatal pig","volume":"268","author":"G Wu","year":"1995","journal-title":"The American journal of physiology"},{"key":"pone.0267357.ref028","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1093\/jas\/skz258.141","article-title":"253 Glutamate and glutamine are the major metabolic fuels in enterocytes of suckling piglets","volume":"97","author":"W He","year":"2019","journal-title":"Journal of animal science"},{"issue":"11","key":"pone.0267357.ref029","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1017\/S1751731119001800","article-title":"Review: The roles and functions of glutamine on intestinal health and performance of weaning pigs.","volume":"13","author":"FJ Ji","year":"2019","journal-title":"Animal: an international journal of animal bioscience"},{"issue":"1","key":"pone.0267357.ref030","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00726-009-0269-0","article-title":"Amino acids: metabolism, functions, and nutrition","volume":"37","author":"G. Wu","year":"2009","journal-title":"Amino acids"},{"key":"pone.0267357.ref031","article-title":"Absorption and metabolic effects of enterally administered glutamine in humans","volume":"260","author":"P D\u00e9chelotte","year":"1991","journal-title":"The American journal of physiology"},{"key":"pone.0267357.ref032","volume-title":"Metabolism of Vascular and Luminal Glutamine by Intestinal Mucosa in Vivo. Glutamine Metabolism in Mammalian Tissues","author":"HG Windmueller","year":"1984"},{"issue":"1","key":"pone.0267357.ref033","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/2049-1891-4-29","article-title":"Effects of creep feeding and supplemental glutamine or glutamine plus glutamate (Aminogut) on pre- and post-weaning growth performance and intestinal health of piglets.","volume":"4","author":"RA Cabrera","year":"2013","journal-title":"Journal of animal science and biotechnology"},{"issue":"6","key":"pone.0267357.ref034","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1093\/jn\/138.6.1025","article-title":"Gene expression is altered in piglet small intestine by weaning and dietary glutamine supplementation","volume":"138","author":"JJ Wang","year":"2008","journal-title":"The Journal of nutrition"},{"issue":"10","key":"pone.0267357.ref035","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1093\/jn\/126.10.2578","article-title":"Dietary glutamine supplementation prevents jejunal atrophy in weaned pigs","volume":"126","author":"G Wu","year":"1996","journal-title":"The Journal of nutrition"},{"issue":"5","key":"pone.0267357.ref036","first-page":"2035","article-title":"Replacing dietary antibiotics with 0.20% l-glutamine in swine nursery diets: impact on health and productivity of pigs following weaning and transport","volume":"97","author":"AW Duttlinger","year":"2019","journal-title":"Journal of animal science"},{"issue":"11","key":"pone.0267357.ref037","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1093\/jn\/nxz155","article-title":"l-Glutamine Represses the Unfolded Protein Response in the Small Intestine of Weanling Piglets","volume":"149","author":"Y He","year":"2019","journal-title":"The Journal of nutrition"},{"issue":"1","key":"pone.0267357.ref038","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s00726-009-0243-x","article-title":"L-Glutamine or L-alanyl-L-glutamine prevents oxidant- or endotoxin-induced death of neonatal enterocytes","volume":"37","author":"TE Haynes","year":"2009","journal-title":"Amino acids"},{"issue":"7","key":"pone.0267357.ref039","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.2527\/jas.2010-3614","article-title":"Triennial Growth Symposium: important roles for L-glutamine in swine nutrition and production","author":"G Wu","year":"2011","journal-title":"Journal of animal science"},{"issue":"1","key":"pone.0267357.ref040","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/2049-1891-3-2","article-title":"Glutamine and glutamate supplementation raise milk glutamine concentrations in lactating gilts","volume":"3","author":"HE Manso","year":"2012","journal-title":"J Anim Sci Biotechnol"},{"issue":"2","key":"pone.0267357.ref041","doi-asserted-by":"crossref","first-page":"329","DOI":"10.2527\/jas.2010-2970","article-title":"Limited and excess dietary protein during gestation affects growth and compositional traits in gilts and impairs offspring fetal growth","volume":"89","author":"C Rehfeldt","year":"2011","journal-title":"Journal of animal science"},{"key":"pone.0267357.ref042","first-page":"1","article-title":"Glutamine supplementation moderately affects growth, plasma metabolite and free amino acid patterns in neonatal low birthweight piglets","author":"Z Li","year":"2022","journal-title":"The British journal of nutrition"},{"key":"pone.0267357.ref043","author":"M Mulisch","year":"2010","journal-title":"Romeis Mikroskopische Technik"},{"issue":"3","key":"pone.0267357.ref044","article-title":"Effect of Dietary Zinc Oxide on Morphological Characteristics, Mucin Composition and Gene Expression in the Colon of Weaned Piglets.","volume":"9","author":"P Liu","year":"2014","journal-title":"Plos One"},{"issue":"1","key":"pone.0267357.ref045","doi-asserted-by":"crossref","DOI":"10.1186\/s40104-019-0380-3","article-title":"Bacillus sp. probiotic supplementation diminish the Escherichia coli F4ac infection in susceptible weaned pigs by influencing the intestinal immune response, intestinal microbiota and blood metabolomics","volume":"10","author":"D Luise","year":"2019","journal-title":"Journal of animal science and biotechnology"},{"key":"pone.0267357.ref046","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1053\/jcpa.2000.0450","article-title":"The distribution of leucocyte subsets in the small intestine of healthy cats","volume":"124","author":"N Waly","year":"2001","journal-title":"Journal of comparative pathology"},{"issue":"2","key":"pone.0267357.ref047","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1053\/jcpa.1998.0262","article-title":"Analysis of leucocyte subsets in the canine intestine","volume":"120","author":"AJ German","year":"1999","journal-title":"Journal of comparative pathology"},{"issue":"3","key":"pone.0267357.ref048","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/jpn.12490","article-title":"Influence of medium-chain fatty acids and short-chain organic acids on jejunal morphology and intra-epithelial immune cells in weaned piglets","volume":"101","author":"F Ferrara","year":"2017","journal-title":"Journal of Animal Physiology and Animal Nutrition"},{"issue":"2","key":"pone.0267357.ref049","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.acthis.2009.09.009","article-title":"Demonstration of substances of innate immunity in the esophageal epithelium of domesticated mammals. Part I\u2014Methods and evaluation of comparative fixation.","volume":"113","author":"IN Hornickel","year":"2011","journal-title":"Acta histochemica"},{"issue":"11","key":"pone.0267357.ref050","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0076705","article-title":"Effects on transcriptional regulation and lipid droplet characteristics in the liver of female juvenile pigs after early postnatal feed restriction and refeeding are dependent on birth weight","volume":"8","author":"C Nebendahl","year":"2013","journal-title":"Plos One"},{"issue":"1","key":"pone.0267357.ref051","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1006\/abio.1998.3091","article-title":"Quantification of glutamine in proteins and peptides using enzymatic hydrolysis and reverse-phase high-performance liquid chromatography","volume":"269","author":"M Tsao","year":"1999","journal-title":"Analytical biochemistry"},{"issue":"14","key":"pone.0267357.ref052","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1002\/pmic.200900789","article-title":"Effect of a high-protein diet on food intake and liver metabolism during pregnancy, lactation and after weaning in mice","volume":"10","author":"B Kuhla","year":"2010","journal-title":"Proteomics"},{"issue":"4","key":"pone.0267357.ref053","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.3168\/jds.2012-6267","article-title":"Increased milk protein synthesis in response to exogenous growth hormone is associated with changes in mechanistic (mammalian) target of rapamycin (mTOR)C1-dependent and independent cell signaling.","volume":"96","author":"M Sciascia","year":"2013","journal-title":"Journal of dairy science"},{"issue":"3","key":"pone.0267357.ref054","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.toxlet.2006.05.006","article-title":"Effects of the Fusarium toxin deoxynivalenol on tissue protein synthesis in pigs","volume":"165","author":"S Danicke","year":"2006","journal-title":"Toxicology letters"},{"issue":"3","key":"pone.0267357.ref055","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1093\/jn\/nxy296","article-title":"Substitution of Dietary Sulfur Amino Acids by DL-2-hydroxy-4-Methylthiobutyric Acid Increases Remethylation and Decreases Transsulfuration in Weaned Piglets","volume":"149","author":"I Rasch","year":"2019","journal-title":"The Journal of nutrition"},{"issue":"1","key":"pone.0267357.ref056","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/S0304-3940(02)01423-4","article-title":"Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data.","volume":"339","author":"C Ramakers","year":"2003","journal-title":"Neuroscience letters"},{"issue":"4","key":"pone.0267357.ref057","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","article-title":"The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments","volume":"55","author":"SA Bustin","year":"2009","journal-title":"Clinical chemistry"},{"issue":"11","key":"pone.0267357.ref058","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1005752","article-title":"mixOmics: An R package for \u2019omics feature selection and multiple data integration","volume":"13","author":"F Rohart","year":"2017","journal-title":"PLoS computational biology"},{"issue":"7","key":"pone.0267357.ref059","doi-asserted-by":"crossref","DOI":"10.3390\/metabo10070278","article-title":"Can We Trust Score Plots?","volume":"10","author":"M Bevilacqua","year":"2020","journal-title":"Metabolites"},{"key":"pone.0267357.ref060","author":"M. Torchiano","year":"2020","journal-title":"Effsize\u2014a package for efficient effect size computation"},{"key":"pone.0267357.ref061","article-title":"qvalue: Q-value estimation for false discovery rate control","author":"BA Storey JD","year":"2021","journal-title":"R package version 2.24.0."},{"issue":"1","key":"pone.0267357.ref062","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Y Benjamini","year":"1995","journal-title":"Journal of the Royal Statistical Society Series B (Methodological)."},{"issue":"1","key":"pone.0267357.ref063","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s40104-020-00538-y","article-title":"Intrauterine growth restriction alters nutrient metabolism in the intestine of porcine offspring","volume":"12","author":"T Li","year":"2021","journal-title":"Journal of animal 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cells","volume":"23","author":"PB Xi","year":"2012","journal-title":"The Journal of nutritional biochemistry"},{"issue":"1","key":"pone.0267357.ref067","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s00726-014-1842-8","article-title":"L-Glutamine enhances enterocyte growth via activation of the mTOR signaling pathway independently of AMPK","volume":"47","author":"D Yi","year":"2015","journal-title":"Amino Acids"},{"issue":"2","key":"pone.0267357.ref068","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1177\/014860719902300247","article-title":"A comparison of parenteral and enteral feeding in neonatal piglets, including an assessment of the utilization of a glutamine-rich, pediatric elemental diet","volume":"23","author":"RF Bertolo","year":"1999","journal-title":"JPEN Journal of parenteral and enteral nutrition"},{"issue":"12","key":"pone.0267357.ref069","doi-asserted-by":"crossref","DOI":"10.3390\/ijms18122617","article-title":"l-Glutamine Attenuates Apoptosis 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journal of animal sciences"},{"issue":"3","key":"pone.0267357.ref072","doi-asserted-by":"crossref","first-page":"634","DOI":"10.2527\/2005.833634x","article-title":"Effect of glutamine and spray-dried plasma on growth performance, small intestinal morphology, and immune responses of Escherichia coli K88+-challenged weaned pigs","volume":"83","author":"GF Yi","year":"2005","journal-title":"Journal of animal science"},{"issue":"11","key":"pone.0267357.ref073","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1093\/jn\/127.11.2253","article-title":"Glutamine supplementation maintains intramuscular glutamine concentrations and normalizes lymphocyte function in infected early weaned pigs","volume":"127","author":"SS Yoo","year":"1997","journal-title":"The Journal of nutrition"},{"issue":"11","key":"pone.0267357.ref074","doi-asserted-by":"crossref","DOI":"10.3390\/nu10111564","article-title":"Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation.","volume":"10","author":"V Cruzat","year":"2018","journal-title":"Nutrients"},{"issue":"11","key":"pone.0267357.ref075","doi-asserted-by":"crossref","DOI":"10.3390\/ani10111976","article-title":"Effects of Oral Glutamine Supplementation on Early Postnatal Muscle Morphology in Low and Normal Birth Weight Piglets.","volume":"10","author":"Y Zhao","year":"2020","journal-title":"Animals: an open access journal from MDPI"},{"issue":"3","key":"pone.0267357.ref076","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1093\/jn\/128.3.606","article-title":"Catabolism dominates the first-pass intestinal metabolism of dietary essential amino acids in milk protein-fed piglets","volume":"128","author":"B Stoll","year":"1998","journal-title":"The Journal of nutrition"},{"key":"pone.0267357.ref077","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.livsci.2015.11.003","article-title":"Birth weight has no influence on the morphology, digestive capacity and motility of the small intestine in suckling pigs","volume":"182","author":"V Huygelen","year":"2015","journal-title":"Livestock science"},{"issue":"2","key":"pone.0267357.ref078","first-page":"231","article-title":"Impact of intrauterine growth retardation on the gastrointestinal tract and the pancreas in newborn pigs","volume":"18","author":"RJ Xu","year":"1994","journal-title":"Journal of pediatric gastroenterology and nutrition"},{"issue":"2","key":"pone.0267357.ref079","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1096\/fj.15-274779","article-title":"Intrauterine growth restriction in neonatal piglets affects small intestinal mucosal permeability and mRNA expression of redox-sensitive genes","volume":"30","author":"W Wang","year":"2016","journal-title":"FASEB journal: official publication of the Federation of American Societies for Experimental Biology"},{"issue":"9","key":"pone.0267357.ref080","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.3390\/ani11092561","article-title":"Low Birth Weight Disturbs the Intestinal Redox Status and Mitochondrial Morphology and Functions in Newborn Piglets.","volume":"11","author":"J Chen","year":"2021","journal-title":"Animals: an open access journal from MDPI"},{"key":"pone.0267357.ref081","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.livsci.2013.10.016","article-title":"Growth and small intestine histomorphology of low and normal birth weight piglets during the early suckling period","volume":"158","author":"M Wiyaporn","year":"2013","journal-title":"Livestock science"},{"key":"pone.0267357.ref082","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.tvjl.2019.02.006","article-title":"Blood glucose, amino acid profiles and nutrient transporter gene expressions in the small intestine of low and normal birthweight piglets during the early suckling period.","volume":"247","author":"B Thongsong","year":"2019","journal-title":"The Veterinary Journal."},{"issue":"5","key":"pone.0267357.ref083","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1159\/000492552","article-title":"Suckling Piglet Intestinal Enterocyte Nutrient Metabolism Changes.","volume":"48","author":"Q Wang","year":"2018","journal-title":"Cellular physiology and biochemistry: international journal of experimental cellular physiology, biochemistry, and pharmacology."},{"issue":"1","key":"pone.0267357.ref084","doi-asserted-by":"crossref","DOI":"10.1152\/ajpregu.2001.280.1.R241","article-title":"Intestinal apical amino acid absorption during development of the pig","volume":"280","author":"RK Buddington","year":"2001","journal-title":"American journal of physiology Regulatory, integrative and comparative physiology."},{"issue":"1","key":"pone.0267357.ref085","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/S0034-5288(18)30482-X","article-title":"Alterations in piglet small intestinal structure at weaning","volume":"40","author":"DJ Hampson","year":"1986","journal-title":"Research in veterinary science"},{"issue":"4","key":"pone.0267357.ref086","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1023\/A:1014768806773","article-title":"Stereologic characteristics of pig small intestine during normal development","volume":"47","author":"C Van Ginneken","year":"2002","journal-title":"Digestive diseases and sciences"},{"issue":"12","key":"pone.0267357.ref087","doi-asserted-by":"crossref","first-page":"3879","DOI":"10.1128\/AEM.00589-13","article-title":"Butyrate-producing bacteria, including mucin degraders, from the swine intestinal tract","volume":"79","author":"UY Levine","year":"2013","journal-title":"Applied and environmental microbiology"},{"issue":"11","key":"pone.0267357.ref088","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.3382\/ps.2007-00222","article-title":"Bacterial modulation of small intestinal goblet cells and mucin composition during early posthatch development of poultry","volume":"86","author":"RE Forder","year":"2007","journal-title":"Poultry science"},{"issue":"4","key":"pone.0267357.ref089","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.2527\/jas.2008-1330","article-title":"Board-invited review: porcine mucosal immunity of the gastrointestinal tract","volume":"87","author":"TE Burkey","year":"2009","journal-title":"Journal of animal science"},{"issue":"3","key":"pone.0267357.ref090","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1203\/00006450-199103000-00004","article-title":"The postnatal development of gut lamina propria lymphocytes: number, proliferation, and T and B cell subsets in conventional and germ-free pigs","volume":"29","author":"HJ Rothkotter","year":"1991","journal-title":"Pediatric research"},{"issue":"1","key":"pone.0267357.ref091","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0165-2427(81)90038-6","article-title":"The differential localization of IgA, IgM and IgG in the gut of suckled neonatal piglets","volume":"2","author":"JE Butler","year":"1981","journal-title":"Veterinary immunology and immunopathology"},{"issue":"3","key":"pone.0267357.ref092","first-page":"493","article-title":"The relative distribution of IgM and IgA cells in intestinal mucosa and lymphoid tissues of the young unweaned pig and their significance in ontogenesis of secretory immunity","volume":"24","author":"WD Allen","year":"1973","journal-title":"Immunology"},{"issue":"4","key":"pone.0267357.ref093","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1046\/j.1439-0442.2002.00407.x","article-title":"Biochemical intestinal parameters in pigs reared outdoors and indoors, and in germ-free pigs","volume":"49","author":"E Collinder","year":"2002","journal-title":"Journal of veterinary medicine A, Physiology, pathology, clinical medicine."},{"issue":"6","key":"pone.0267357.ref094","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.2527\/2006.8461375x","article-title":"Intestinal morphology and enzymatic activity in newly weaned pigs fed contrasting fiber concentrations and fiber properties","volume":"84","author":"MS Hedemann","year":"2006","journal-title":"Journal of animal science"},{"issue":"1","key":"pone.0267357.ref095","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1096\/fj.201902514R","article-title":"Post-natal co-development of the microbiota and gut barrier function follows different paths in the small and large intestine in piglets","volume":"34","author":"AP Arnaud","year":"2020","journal-title":"FASEB journal: official publication of the Federation of American Societies for Experimental Biology"},{"issue":"4","key":"pone.0267357.ref096","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1177\/0148607193017004307","article-title":"Effect of Glutamine on Protein-Synthesis in Isolated Intestinal Epithelial-Cells.","volume":"17","author":"T Higashiguchi","year":"1993","journal-title":"JPEN Journal of parenteral and enteral nutrition"},{"key":"pone.0267357.ref097","first-page":"7","article-title":"Into the unknown\u2014the death pathways in the neonatal gut epithelium","volume":"56","author":"MM Godlewski","year":"2005","journal-title":"Journal of physiology and pharmacology: an official journal of the Polish Physiological Society"},{"key":"pone.0267357.ref098","article-title":"Birth oxidative stress and the development of an antioxidant system in newborn piglets","volume":"47","author":"J Yin","year":"2013","journal-title":"Free radical research"},{"issue":"2","key":"pone.0267357.ref099","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/0304-4165(92)90073-4","article-title":"Catalase, superoxide dismutase and glutathione peroxidase activities of lung and liver during human development","volume":"1117","author":"MC McElroy","year":"1992","journal-title":"Biochimica et biophysica acta General subjects"}],"container-title":["PLOS 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