{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T22:49:10Z","timestamp":1787698150617,"version":"build-2784847793"},"reference-count":62,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,7,30]],"date-time":"2019-07-30T00:00:00Z","timestamp":1564444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Key R&amp;D Program of China","award":["2017YFD0500505"],"award-info":[{"award-number":["2017YFD0500505"]}]},{"name":"the Fundamental Research Funds for the Central Universities, China","award":["KYZ201722"],"award-info":[{"award-number":["KYZ201722"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Galacto-oligosaccharides (GOS), functional oligosaccharides with natural characteristics, are important active substances in milk that play an important role in the development of intestinal microbiota and the immune system of newborns. The intestinal maturation of piglets resembles that of human newborns and infants. Therefore, we used the newborn piglet model to study the effects of early-life GOS intervention. Six litters of neonatal piglets (10 piglets per litter) with the same average birth weight were divided into control (CON) and GOS (GOS) groups in each litter. Piglets in the GOS group were given 10 mL of GOS solution daily during the first week after birth, while piglets in the CON group were given the same dose of physiological saline orally. One pig per group from each litter was euthanized on day 8 and day 21. Results revealed that ileal microbiota composition was significantly enriched in Lactobacillus and unclassified Lactobacillaceae, and reduced in Clostridium sensu stricto on day 8 and day 21 after GOS intervention. Additionally, Escherichia significantly decreased on day 21 following the early-life GOS intervention. Moreover, the content of microbial metabolites, endocrine peptides, and the mRNA expression of anti-inflammatory cytokines and antimicrobial peptides increased in the GOS group. These findings provide guidelines for early prebiotic supplementation for lactating newborns.<\/jats:p>","DOI":"10.3390\/nu11081753","type":"journal-article","created":{"date-parts":[[2019,7,30]],"date-time":"2019-07-30T11:15:56Z","timestamp":1564485356000},"page":"1753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Changes in Ileal Microbial Composition and Microbial Metabolism by an Early-Life Galacto-Oligosaccharides Intervention in a Neonatal Porcine Model"],"prefix":"10.3390","volume":"11","author":[{"given":"Shiyi","family":"Tian","sequence":"first","affiliation":[{"name":"National center for International Research on Animal Gut Nutrition, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, Laboratory of Gastrointestinal Microbiology, National Experimental Teaching Demonstration Center of Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jue","family":"Wang","sequence":"additional","affiliation":[{"name":"National center for International Research on Animal Gut Nutrition, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, Laboratory of Gastrointestinal Microbiology, National Experimental Teaching Demonstration Center of Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Yu","sequence":"additional","affiliation":[{"name":"National center for International Research on Animal Gut Nutrition, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, Laboratory of Gastrointestinal Microbiology, National Experimental Teaching Demonstration Center of Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9496-6276","authenticated-orcid":false,"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"National center for International Research on Animal Gut Nutrition, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, Laboratory of Gastrointestinal Microbiology, National Experimental Teaching Demonstration Center of Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyun","family":"Zhu","sequence":"additional","affiliation":[{"name":"National center for International Research on Animal Gut Nutrition, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, Laboratory of Gastrointestinal Microbiology, National Experimental Teaching Demonstration Center of Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"367","DOI":"10.3920\/BM2010.0027","article-title":"Early life: Gut microbiota and immune development in infancy","volume":"1","author":"Martin","year":"2010","journal-title":"Benef. Microbes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1126\/science.1223490","article-title":"Interactions between the microbiota and the immune system","volume":"336","author":"Hooper","year":"2012","journal-title":"Science"},{"key":"ref_3","first-page":"S36","article-title":"NMR-based metabonomics analysis of mouse urine and fecal extracts following oral treatment with the broad-spectrum antibiotic enrofloxacin (Baytril)","volume":"47","author":"Goodpaster","year":"2009","journal-title":"Magn. Reson. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.3389\/fmicb.2018.01166","article-title":"Marked Response in Microbial Community and Metabolism in the Ileum and Cecum of Suckling Piglets After Early Antibiotics Exposure","volume":"9","author":"Yu","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Schokker, D., Zhang, J., Zhang, L.-L., Vastenhouw, S.A., Heilig, H.G.H.J., Smidt, H., Rebel, J.M.J., and Smits, M.A. (2014). Early-Life Environmental Variation Affects Intestinal Microbiota and Immune Development in New-Born Piglets. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100040"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/j.1399-3038.2011.01258.x","article-title":"Direct experimental evidence that early-life farm environment influences regulation of immune responses","volume":"23","author":"Lewis","year":"2012","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Schachtschneider, K.M., Yeoman, C.J., Isaacson, R.E., White, B.A., Schook, L.B., and Pieters, M. (2013). Modulation of Systemic Immune Responses through Commensal Gastrointestinal Microbiota. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053969"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1016\/j.cell.2012.04.037","article-title":"Gut Immune Maturation Depends on Colonization with a Host-Specific Microbiota","volume":"149","author":"Chung","year":"2012","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1111\/j.1462-2920.2006.01009.x","article-title":"Post-natal development of the porcine microbiota composition and activities","volume":"8","author":"Konstantinov","year":"2006","journal-title":"Environ. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1017\/S0007114515000823","article-title":"Oligosaccharides in infant formula: More evidence to validate the role of prebiotics","volume":"113","author":"Vandenplas","year":"2015","journal-title":"Br. J. Nutr."},{"key":"ref_11","first-page":"979","article-title":"Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut","volume":"7","author":"Selak","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1021\/jf802484j","article-title":"In vitro fermentation profiles, gas production rates, and microbiota modulation as affected by certain fructans, galactooligosaccharides, and polydextrose","volume":"57","author":"Hernot","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3390\/nu7010017","article-title":"The impact of diet and lifestyle on gut microbiota and human health","volume":"7","author":"Conlon","year":"2015","journal-title":"Nutrients"},{"key":"ref_14","first-page":"43","article-title":"Functional properties of the second generation prebiotic Galacto-oligosaccharide (B-GOS)","volume":"20","author":"Tzortzis","year":"2009","journal-title":"Agro Food Ind. Hi-Tech"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"247","DOI":"10.3920\/BM2015.0114","article-title":"High purity galacto-oligosaccharides (GOS) enhance specific Bifidobacterium species and their metabolic activity in the mouse gut microbiome","volume":"7","author":"Arthur","year":"2016","journal-title":"Benef. Microbes"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1017\/S0007114515001889","article-title":"Influence of galacto-oligosaccharide mixture (B-GOS) on gut microbiota, immune parameters and metabonomics in elderly persons","volume":"114","author":"Vulevic","year":"2015","journal-title":"Br. J. Nutr."},{"key":"ref_17","first-page":"34","article-title":"Prebiotics and lipid metabolism: A review","volume":"21","author":"Sharma","year":"2015","journal-title":"Altern. Ther. Health Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.nfs.2016.03.001","article-title":"Effects of probiotics, prebiotics, and synbiotics on mineral metabolism in ovariectomized rats\u2014Impact of bacterial mass, intestinal absorptive area and reduction of bone turn-over","volume":"3","author":"Adolphi","year":"2016","journal-title":"NFS J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1017\/S0954422413000152","article-title":"Use of pigs as a potential model for research into dietary modulation of the human gut microbiota","volume":"26","author":"Heinritz","year":"2013","journal-title":"Nutr. Res. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4736","DOI":"10.1038\/s41598-018-23198-5","article-title":"Kommedal, \u00d8yvind Species Level Description of the Human Ileal Bacterial Microbiota","volume":"8","author":"Villmones","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.fct.2005.10.012","article-title":"90-Day oral (gavage) study in rats with galactooligosaccharides syrup","volume":"44","author":"Anthony","year":"2006","journal-title":"Food Chem. Toxicol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"453","DOI":"10.3920\/BM2015.0168","article-title":"Infant formula with galacto-oligosaccharides (OM55N) stimulates the growth of indigenous bifidobacteria in healthy term infants","volume":"7","author":"Matsuki","year":"2016","journal-title":"Benef. Microbes"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1631\/jzus.B0820261","article-title":"Prebiotic oligosaccharides change the concentrations of short-chain fatty acids and the microbial population of mouse bowel","volume":"10","author":"Pan","year":"2009","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3854","DOI":"10.1128\/AEM.64.10.3854-3859.1998","article-title":"Temperature Gradient Gel Electrophoresis Analysis of 16S rRNA from Human Fecal Samples Reveals Stable and Host-Specific Communities of Active Bacteria","volume":"64","author":"Zoetendal","year":"1998","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1007\/s00284-018-1442-z","article-title":"The Changes of Colonic Bacterial Composition and Bacterial Metabolism Induced by an Early Food Introduction in a Neonatal Porcine Model","volume":"75","author":"Shi","year":"2018","journal-title":"Curr. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1093\/bioinformatics\/btq461","article-title":"Search and clustering orders of magnitude faster than BLAST","volume":"26","author":"Edgar","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5261","DOI":"10.1128\/AEM.00062-07","article-title":"Na\u00efve Bayesian Classifier for Rapid Assignment of rRNA Sequences into the New Bacterial Taxonomy","volume":"73","author":"Wang","year":"2007","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7537","DOI":"10.1128\/AEM.01541-09","article-title":"Introducing mothur: Open-Source, Platform-Independent, Community-Supported Software for Describing and Comparing Microbial Communities","volume":"75","author":"Schloss","year":"2009","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1021\/acs.jafc.8b05679","article-title":"Response of Colonic Mucosa-Associated Microbiota Composition, Mucosal Immune Homeostasis, and Barrier Function to Early Life Galactooligosaccharides Intervention in Suckling Piglets","volume":"67","author":"Wang","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s40104-018-0290-9","article-title":"Effects of galacto-oligosaccharides on growth and gut function of newborn suckling piglets","volume":"9","author":"Tian","year":"2018","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1039\/C7FO01720K","article-title":"Effects of a galacto-oligosaccharide-rich diet on fecal microbiota and metabolite profiles in mice","volume":"9","author":"Cheng","year":"2018","journal-title":"Food Funct."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1039\/C7FO00031F","article-title":"Effects of different oligosaccharides at various dosages on the composition of gut microbiota and short-chain fatty acids in mice with constipation","volume":"8","author":"Wang","year":"2017","journal-title":"Food Funct."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mariat, D., Firmesse, O., Levenez, F., Guimar\u0103es, V., Sokol, H., Dor\u00e9, J., Corthier, G., and Furet, J.-P. (2009). The Firmicutes\/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol., 9.","DOI":"10.1186\/1471-2180-9-123"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1002\/pmic.201500117","article-title":"Functional proteomics within the genus Lactobacillus","volume":"16","author":"Angelis","year":"2016","journal-title":"Proteomics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1111\/jam.13364","article-title":"Probiotic roles of Lactobacillus sp. in swine: Insights from gut microbiota","volume":"122","author":"Valeriano","year":"2017","journal-title":"J. Appl. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1017\/S175173111000193X","article-title":"Probiotics\u2014Do they have a role in the pig industry?","volume":"5","author":"Kenny","year":"2011","journal-title":"Animal"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"762","DOI":"10.3389\/fmicb.2015.00762","article-title":"Reutericyclin producing Lactobacillus reuteri modulates development of fecal microbiota in weanling pigs","volume":"6","author":"Yang","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1073\/pnas.0337704100","article-title":"Complete genome sequence of Lactobacillus plantarum WCFS1","volume":"100","author":"Kleerebezem","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"78","DOI":"10.5713\/ajas.16.0285","article-title":"Microbial composition in different gut locations of weaning piglets receiving antibiotics","volume":"30","author":"Li","year":"2017","journal-title":"Asian Australas. J. Anim. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1099\/ijs.0.041376-0","article-title":"Description of Alloprevotella rava gen. nov., sp. nov., isolated from the human oral cavity, and reclassification of Prevotella tannerae Moore et al. 1994 as Alloprevotella tannerae gen. nov., comb. nov","volume":"63","author":"Downes","year":"2013","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/5147571","article-title":"Interferon Tau Affects Mouse Intestinal Microbiota and Expression of IL-17","volume":"2016","author":"Ren","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"43412","DOI":"10.1038\/srep43412","article-title":"Moderate dietary protein restriction alters the composition of gut microbiota and improves ileal barrier function in adult pig model","volume":"7","author":"Fan","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.anaerobe.2015.12.009","article-title":"Effects of the dietary protein level on the microbial composition and metabolomic profile in the hindgut of the pig","volume":"38","author":"Zhou","year":"2016","journal-title":"Anaerobe"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1017\/S1751731110000558","article-title":"Effect of mannanoligosaccharides supplementation on caecal microbial activity of rabbits","volume":"4","author":"Bovera","year":"2010","journal-title":"Animal"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1186\/s40104-015-0042-z","article-title":"A review of the effects of dietary organic acids fed to swine","volume":"6","author":"Suiryanrayna","year":"2015","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.3389\/fmicb.2018.02344","article-title":"Response of Gut Microbiota to Dietary Fiber and Metabolic Interaction With SCFAs in Piglets","volume":"9","author":"Liu","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"16269","DOI":"10.1038\/s41598-017-16560-6","article-title":"Insect-based diet, a promising nutritional source, modulates gut microbiota composition and SCFAs production in laying hens","volume":"7","author":"Borrelli","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/nature11552","article-title":"Functional interactions between the gut microbiota and host metabolism","volume":"489","author":"Tremaroli","year":"2012","journal-title":"Nature"},{"key":"ref_50","first-page":"E460","article-title":"Frontiers in glucagon-like peptide-2: Multiple actions, multiple mediators","volume":"293","author":"Brubaker","year":"2007","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s11154-014-9288-6","article-title":"Gut microbiota and GLP-1","volume":"15","author":"Everard","year":"2014","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1053\/j.gastro.2011.09.014","article-title":"Loss of Glucagon-Like Peptide-2-Induced Proliferation Following Intestinal Epithelial Insulin-Like Growth Factor-1\u2013Receptor Deletion","volume":"141","author":"Rowland","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.coph.2013.09.008","article-title":"Gut microbiota, enteroendocrine functions and metabolism","volume":"13","author":"Cani","year":"2013","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Miyamoto, J., Hasegawa, S., Kasubuchi, M., Ichimura, A., Nakajima, A., and Kimura, I. (2016). Nutritional Signaling via Free Fatty Acid Receptors. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17040450"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3552","DOI":"10.1210\/en.2013-1142","article-title":"GPR41\/FFAR3 and GPR43\/FFAR2 as Cosensors for Short-Chain Fatty Acids in Enteroendocrine Cells vs FFAR3 in Enteric Neurons and FFAR2 in Enteric Leukocytes","volume":"154","author":"Pedersen","year":"2013","journal-title":"Endocrinology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1111\/apa.12700","article-title":"A review of the innate immune defence of the human foetus and newborn, with the emphasis on antimicrobial peptides","volume":"103","author":"Gudmundsson","year":"2014","journal-title":"Acta Paediatr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1017\/S0007114515004997","article-title":"The piglet as a model for studying dietary components in infant diets: Effects of galacto-oligosaccharides on intestinal functions","volume":"115","author":"Alizadeh","year":"2016","journal-title":"Br. J. Nutr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.molimm.2007.06.001","article-title":"Porcine \u03b2-defensin 2 displays broad antimicrobial activity against pathogenic intestinal bacteria","volume":"45","author":"Veldhuizen","year":"2008","journal-title":"Mol. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.syapm.2016.10.001","article-title":"Detection, isolation and characterization of Fusobacterium gastrosuis sp. nov. colonizing the stomach of pigs","volume":"40","author":"Flahou","year":"2017","journal-title":"Syst. Appl. Microbiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1099\/jmm.0.000083","article-title":"Genital carriage of the genus Haemophilus in pregnancy: Species distribution and antibiotic susceptibility","volume":"64","author":"Cardines","year":"2015","journal-title":"J. Med. Microbiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/0304-3959(95)00186-7","article-title":"Immune activation: The role of pro-inflammatory cytokines in inflammation, illness responses and pathological pain states","volume":"63","author":"Watkins","year":"1995","journal-title":"Pain"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1378\/chest.117.4.1162","article-title":"Anti-inflammatory cytokines","volume":"117","author":"Opal","year":"2000","journal-title":"Chest"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/8\/1753\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:11:13Z","timestamp":1760188273000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/8\/1753"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,30]]},"references-count":62,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2019,8]]}},"alternative-id":["nu11081753"],"URL":"https:\/\/doi.org\/10.3390\/nu11081753","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,30]]}}}