{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T01:51:57Z","timestamp":1769737917144,"version":"3.49.0"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,11,2]],"date-time":"2024-11-02T00:00:00Z","timestamp":1730505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,11,2]],"date-time":"2024-11-02T00:00:00Z","timestamp":1730505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100015101","name":"Chicken Farmers of Saskatchewan","doi-asserted-by":"publisher","award":["424357"],"award-info":[{"award-number":["424357"]}],"id":[{"id":"10.13039\/100015101","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008681","name":"Canadian Poultry Research Council","doi-asserted-by":"publisher","award":["424854"],"award-info":[{"award-number":["424854"]}],"id":[{"id":"10.13039\/100008681","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["424679"],"award-info":[{"award-number":["424679"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008921","name":"Saskatchewan Agriculture Development Fund","doi-asserted-by":"crossref","award":["426954"],"award-info":[{"award-number":["426954"]}],"id":[{"id":"10.13039\/100008921","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Animal Sci Biotechnol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Necrotic enteritis (NE) is an economically important disease of broiler chickens caused by <jats:italic>Clostridium perfringens<\/jats:italic> (CP). The pathogenesis, or disease process, of NE is still not clear. This study aimed to identify the alterations of metabolites and metabolic pathways associated with subclinical or clinical NE in CP infected birds and to investigate the possible variations in the metabolic profile of birds infected with different isolates of CP.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methodology<\/jats:title>\n                <jats:p>Using a well-established NE model, the protein content of feed was changed abruptly before exposing birds to CP isolates with different toxin genes combinations (<jats:italic>cpa<\/jats:italic>,<jats:italic> cpb2<\/jats:italic>,<jats:italic> netB<\/jats:italic>,<jats:italic> tpeL<\/jats:italic>; <jats:italic>cpa<\/jats:italic>, <jats:italic>cpb2<\/jats:italic>,<jats:italic> netB<\/jats:italic>; or <jats:italic>cpa<\/jats:italic>,<jats:italic> cpb2<\/jats:italic>). Metabolomics analysis of jejunal contents was performed by a targeted, fully quantitative LC-MS\/MS based assay.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>This study detected statistically significant differential expression of 34 metabolites including organic acids, amino acids, fatty acids, and biogenic amines, including elevation of butyric acid at onset of NE in broiler chickens. Subsequent analysis of broilers infected with CP isolates with different toxin gene combinations confirmed an elevation of butyric acid consistently among 21 differentially expressed metabolites including organic acids, amino acids, and biogenic amines, underscoring its potential role during the development of NE. Furthermore, protein-metabolite network analysis revealed significant alterations in butyric acid and arginine-proline metabolisms.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>This study indicates a significant metabolic difference between CP-infected and non-infected broiler chickens. Among all the metabolites, butyric acid increased significantly in CP-infected birds compared to non-infected healthy broilers. Logistic regression analysis revealed a positive association between butyric acid (coefficient: 1.23, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01) and CP infection, while showing a negative association with amino acid metabolism. These findings suggest that butyric acid could be a crucial metabolite linked to the occurrence of NE in broiler chickens and may serve as an early indicator of the disease at the farm level. Further metabolomic experiments using different NE animal models and field studies are needed to determine the specificity and to validate metabolites associated with NE, regardless of predisposing factors.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40104-024-01105-5","type":"journal-article","created":{"date-parts":[[2024,11,2]],"date-time":"2024-11-02T01:01:58Z","timestamp":1730509318000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Elevated levels of butyric acid in the jejunum of an animal model of broiler chickens: from early onset of Clostridium perfringens infection to clinical disease of necrotic enteritis"],"prefix":"10.1186","volume":"15","author":[{"given":"Hemlata","family":"Gautam","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noor Ahmad","family":"Shaik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Babajan","family":"Banaganapalli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelly","family":"Popowich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iresha","family":"Subhasinghe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisanework E.","family":"Ayalew","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rupasri","family":"Mandal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David S.","family":"Wishart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suresh","family":"Tikoo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susantha","family":"Gomis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,11,2]]},"reference":[{"key":"1105_CR1","doi-asserted-by":"publisher","unstructured":"Navarro MA, McClane BA, Uzal FA. Mechanisms of action and cell death associated with Clostridium perfringens toxins. Toxins (Basel). 2018;10(5):212. https:\/\/doi.org\/10.3390\/toxins10050212.","DOI":"10.3390\/toxins10050212"},{"issue":"1","key":"1105_CR2","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s12967-023-04728-w","volume":"22","author":"H Gautam","year":"2024","unstructured":"Gautam H, Ayalew LE, Shaik NA, Subhasinghe I, Popowich S, Chow-Lockerbie B, et al. Exploring the predictive power of jejunal microbiome composition in clinical and subclinical necrotic enteritis caused by Clostridium perfringens: insights from a broiler chicken model. J Transl Med. 2024;22(1):80. https:\/\/doi.org\/10.1186\/s12967-023-04728-w.","journal-title":"J Transl Med"},{"key":"1105_CR3","unstructured":"Wade B, Keyburn A. The true cost of necrotic enteritis. World Poult. 2015;31:16\u20137. https:\/\/www.poultryworld.net\/Meat\/Articles\/2015\/10\/The-true-cost-of-necrotic-enteritis-2699819W\/. Accessed 2 Apr 2024."},{"issue":"2","key":"1105_CR4","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1089\/fpd.2012.1316","volume":"10","author":"JE Grass","year":"2013","unstructured":"Grass JE, Gould LH, Mahon BE. Epidemiology of foodborne disease outbreaks caused by Clostridium perfringens, United States, 1998\u20132010. Foodborne Pathog Dis. 2013;10(2):131\u20136. https:\/\/doi.org\/10.1089\/fpd.2012.1316.","journal-title":"Foodborne Pathog Dis"},{"issue":"1","key":"1105_CR5","doi-asserted-by":"publisher","first-page":"14541","DOI":"10.1038\/s41598-019-51104-0","volume":"9","author":"H Wang","year":"2019","unstructured":"Wang H, Latorre JD, Bansal M, Abraha M, Al-Rubaye B, Tellez-Isaias G, et al. Microbial metabolite deoxycholic acid controls Clostridium perfringens-induced chicken necrotic enteritis through attenuating inflammatory cyclooxygenase signaling. Sci Rep. 2019;9:14541. https:\/\/doi.org\/10.1038\/s41598-019-51104-0.","journal-title":"Sci Rep"},{"issue":"3\u20134","key":"1105_CR6","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.vetmic.2014.01.007","volume":"169","author":"S-B Wu","year":"2014","unstructured":"Wu S-B, Stanley D, Rodgers N, Swick RA, Moore RJ. Two necrotic enteritis predisposing factors, dietary fishmeal and eimeria infection, induce large changes in the caecal microbiota of broiler chickens. Vet Microbiol. 2014;169(3\u20134):188\u201397. https:\/\/doi.org\/10.1016\/j.vetmic.2014.01.007.","journal-title":"Vet Microbiol"},{"issue":"4","key":"1105_CR7","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1111\/jam.14661","volume":"129","author":"X Meng","year":"2020","unstructured":"Meng X, Zhang G, Cao H, Yu D, Fang X, de Vos WM, et al. Gut dysbacteriosis and intestinal disease: mechanism and treatment. J Appl Microbiol. 2020;129(4):787\u2013805. https:\/\/doi.org\/10.1111\/jam.14661.","journal-title":"J Appl Microbiol"},{"issue":"17","key":"1105_CR8","doi-asserted-by":"publisher","first-page":"5880","DOI":"10.1128\/AEM.01616-159","volume":"81","author":"C De Maesschalck","year":"2015","unstructured":"De Maesschalck C, Eeckhaut V, Maertens L, De Lange L, Marchal L, Nezer C, et al. Effects of xylo-oligosaccharides on broiler chicken performance and microbiota. Appl Environ Microbiol. 2015;81(17):5880\u20138. https:\/\/doi.org\/10.1128\/AEM.01616-159.","journal-title":"Appl Environ Microbiol"},{"issue":"1","key":"1105_CR9","doi-asserted-by":"publisher","first-page":"188","DOI":"10.3382\/ps\/pey390","volume":"98","author":"YO Fasina","year":"2019","unstructured":"Fasina YO, Lillehoj HS. Characterization of intestinal immune response to Clostridium perfringens infection in broiler chickens. Poult Sci. 2019;98(1):188\u201398. https:\/\/doi.org\/10.3382\/ps\/pey390.","journal-title":"Poult Sci"},{"key":"1105_CR10","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/978-94-010-0448-0_11","volume":"48","author":"O Fiehn","year":"2002","unstructured":"Fiehn O. Metabolomics\u2013the link between genotypes and phenotypes. Plant Mol Biol. 2002;48:155\u201371. https:\/\/doi.org\/10.1007\/978-94-010-0448-0_11.","journal-title":"Plant Mol Biol"},{"issue":"1","key":"1105_CR11","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1038\/s41392-023-01399-3","volume":"8","author":"S Qiu","year":"2023","unstructured":"Qiu S, Cai Y, Yao H, Lin C, Xie Y, Tang S, et al. Small molecule metabolites: discovery of biomarkers and therapeutic targets. Signal Transduct Target Ther. 2023;8(1):132. https:\/\/doi.org\/10.1038\/s41392-023-01399-3.","journal-title":"Signal Transduct Target Ther"},{"key":"1105_CR12","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.ymeth.2018.04.029","volume":"149","author":"S Lamichhane","year":"2018","unstructured":"Lamichhane S, Sen P, Dickens AM, Ore\u0161i\u010d M, Bertram HC. Gut metabolome meets microbiome: a methodological perspective to understand the relationship between host and microbe. Methods. 2018;149:3\u201312. https:\/\/doi.org\/10.1016\/j.ymeth.2018.04.029.","journal-title":"Methods"},{"issue":"5","key":"1105_CR13","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1016\/j.cmet.2022.03.009","volume":"34","author":"TWF Lung","year":"2022","unstructured":"Lung TWF, Charytonowicz D, Beaumont KG, Shah SS, Sridhar SH, Gorrie CL, et al. Klebsiella pneumoniae induces host metabolic stress that promotes tolerance to pulmonary infection. Cell Metab. 2022;34(5):761\u2013774.e9. https:\/\/doi.org\/10.1016\/j.cmet.2022.03.009.","journal-title":"Cell Metab"},{"key":"1105_CR14","doi-asserted-by":"publisher","unstructured":"Urso A, Prince A. Anti-inflammatory metabolites in the pathogenesis of bacterial infection. Front Cell Infect Microbiol. 2022;12:925746. https:\/\/doi.org\/10.3389\/fcimb.2022.925746.","DOI":"10.3389\/fcimb.2022.925746"},{"issue":"2","key":"1105_CR15","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1073\/pnas.022493799","volume":"99","author":"T Shimizu","year":"2002","unstructured":"Shimizu T, Ohtani K, Hirakawa H, Ohshima K, Yamashita A, Shiba T, et al. Complete genome sequence of Clostridium perfringens, an anaerobic flesh-eater. Proc Natl Acad Sci U S A. 2002;99(2):996\u20131001. https:\/\/doi.org\/10.1073\/pnas.022493799.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1105_CR16","doi-asserted-by":"publisher","unstructured":"Yang Q, Liu J, Wang X, Robinson K, Whitmore MA, Stewart SN, et al. Identification of an intestinal microbiota signature associated with the severity of necrotic enteritis. Front Microbiol. 2021;12:703693. https:\/\/doi.org\/10.3389\/fmicb.2021.703693.","DOI":"10.3389\/fmicb.2021.703693"},{"key":"1105_CR17","doi-asserted-by":"crossref","unstructured":"Wang Y, Xu Y, Xu S, Yang J, Wang K, Zhan X. Bacillus subtilis DSM29784 alleviates negative effects on growth performance in broilers by improving the intestinal health under necrotic enteritis challenge. Front Microbiol. 2021;12:723187.","DOI":"10.3389\/fmicb.2021.723187"},{"issue":"1","key":"1105_CR18","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.aninu.2021.04.003","volume":"8","author":"A Kumar","year":"2022","unstructured":"Kumar A, Toghyani M, Kheravii SK, Pineda L, Han Y, Swick RA, et al. Organic acid blends improve intestinal integrity, modulate short-chain fatty acids profiles and alter microbiota of broilers under necrotic enteritis challenge. Anim Nutr. 2022;8(1):82\u201390. https:\/\/doi.org\/10.1016\/j.aninu.2021.04.003.","journal-title":"Anim Nutr"},{"key":"1105_CR19","doi-asserted-by":"publisher","first-page":"4785","DOI":"10.1038\/s41467-023-40336-4","volume":"14","author":"C Hoskinson","year":"2023","unstructured":"Hoskinson C, Dai DL, Del Bel KL, Becker AB, Moraes TJ, Mandhane PJ, et al. Delayed gut microbiota maturation in the first year of life is a hallmark of pediatric allergic disease. Nat Com. 2023;14:4785. https:\/\/doi.org\/10.1038\/s41467-023-40336-4.","journal-title":"Nat Com"},{"key":"1105_CR20","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.aca.2018.01.021","volume":"1037","author":"J Zheng","year":"2018","unstructured":"Zheng J, Mandal R, Wishart DS. A sensitive, high-throughput LC-MS\/MS method for measuring catecholamines in low volume serum. Anal Chim Acta. 2018;1037:159\u201367. https:\/\/doi.org\/10.1016\/j.aca.2018.01.021.","journal-title":"Anal Chim Acta"},{"issue":"7","key":"1105_CR21","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47. https:\/\/doi.org\/10.1093\/nar\/gkv007.","journal-title":"Nucleic Acids Res"},{"key":"1105_CR22","unstructured":"Blighe K, Rana S, Lewis M. EnhancedVolcano: publication-ready volcano plots with enhanced colouring and labeling. R package version 1.20. 0. 2023. https:\/\/github.com\/kevinblighe\/EnhancedVolcano."},{"issue":"4","key":"1105_CR23","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1007\/s11306-014-0759-2","volume":"11","author":"J Ivanisevic","year":"2015","unstructured":"Ivanisevic J, Benton HP, Rinehart D, Epstein A, Kurczy ME, Boska MD, et al. An interactive cluster heat map to visualize and explore multidimensional metabolomic data. Metabolomics. 2015;11(4):1029\u201334. https:\/\/doi.org\/10.1007\/s11306-014-0759-2.","journal-title":"Metabolomics"},{"key":"1105_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/15366367.2019.1565254","volume":"35","author":"PM Valero-Mora","year":"2010","unstructured":"Valero-Mora PM. ggplot2: elegant graphics for data analysis. J Stat Softw. 2010;35:1\u20133. https:\/\/doi.org\/10.1080\/15366367.2019.1565254.","journal-title":"J Stat Softw"},{"key":"1105_CR25","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/1471-2105-13-24","volume":"13","author":"F Yao","year":"2012","unstructured":"Yao F, Coquery J, L\u00ea Cao K-A. Independent principal component analysis for biologically meaningful dimension reduction of large biological data sets. BMC Bioinformatics. 2012;13:24. https:\/\/doi.org\/10.1186\/1471-2105-13-24.","journal-title":"BMC Bioinformatics"},{"key":"1105_CR26","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1007\/978-1-4939-1258-2_22","volume":"1198","author":"B Xi","year":"2014","unstructured":"Xi B, Gu H, Baniasadi H, Raftery D. Statistical analysis, and modeling of mass spectrometry-based metabolomics data. Methods Mol Biol. 2014;1198:333\u201353. https:\/\/doi.org\/10.1007\/978-1-4939-1258-2_22.","journal-title":"Methods Mol Biol"},{"issue":"W1","key":"1105_CR27","doi-asserted-by":"publisher","first-page":"W388","DOI":"10.1093\/nar\/gkab382","volume":"49","author":"Z Pang","year":"2021","unstructured":"Pang Z, Chong J, Zhou G, de Lima Morais DA, Chang L, Barrette M, et al. MetaboAnalyst 5.0: narrowing the gap between raw spectra and functional insights. Nucleic Acids Res. 2021;49(W1):W388\u2013396. https:\/\/doi.org\/10.1093\/nar\/gkab382.","journal-title":"Nucleic Acids Res"},{"key":"1105_CR28","doi-asserted-by":"publisher","unstructured":"Kuhn M, Szklarczyk D, Pletscher-Frankild S, Blicher TH, Von Mering C, Jensen LJ, et al. STITCH 4: integration of protein\u2013chemical interactions with user data. Nucleic Acids Res. 2014;42(D1):D401\u20137. https:\/\/doi.org\/10.1093\/nar\/gkt1207.","DOI":"10.1093\/nar\/gkt1207"},{"issue":"1","key":"1105_CR29","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1186\/s12859-023-05225-z","volume":"24","author":"M Utriainen","year":"2023","unstructured":"Utriainen M, Morris JH. clusterMaker2: a major update to clusterMaker, a multi-algorithm clustering app for Cytoscape. BMC Bioinformatics. 2023;24:134. https:\/\/doi.org\/10.1186\/s12859-023-05225-z.","journal-title":"BMC Bioinformatics"},{"issue":"1","key":"1105_CR30","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/s41426-018-0144-8","volume":"7","author":"R Kiu","year":"2018","unstructured":"Kiu R, Hall LJ. An update on the human and animal enteric pathogen Clostridium perfringens. Emerg Microbes Infect. 2018;7(1):141. https:\/\/doi.org\/10.1038\/s41426-018-0144-8.","journal-title":"Emerg Microbes Infect"},{"issue":"1","key":"1105_CR31","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1128\/JB.182.1.57-66.2000","volume":"182","author":"JK Cheung","year":"2000","unstructured":"Cheung JK, Rood JI. The VirR response regulator from Clostridium perfringens binds independently to two imperfect direct repeats located upstream of the pfoA promoter. J Bacteriol. 2000;182(1):57\u201366. https:\/\/doi.org\/10.1128\/JB.182.1.57-66.2000.","journal-title":"J Bacteriol"},{"issue":"5","key":"1105_CR32","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/j.jbiosc.2017.12.019","volume":"125","author":"K Adachi","year":"2018","unstructured":"Adachi K, Ohtani K, Kawano M, Singh RP, Yousuf B, Sonomoto K, et al. Metabolic dependent and independent pH-drop shuts down VirSR quorum sensing in Clostridium perfringens. J Biosci Bioeng. 2018;125(5):525\u201331. https:\/\/doi.org\/10.1016\/j.jbiosc.2017.12.019.","journal-title":"J Biosci Bioeng"},{"issue":"1","key":"1105_CR33","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1080\/21505594.2021.1886777","volume":"12","author":"I Mehdizadeh Gohari","year":"2021","unstructured":"Mehdizadeh Gohari I, Navarro A, Li M, Shrestha J, Uzal A, McClane B. Pathogenicity and virulence of Clostridium perfringens. Virulence. 2021;12(1):723\u201353. https:\/\/doi.org\/10.1080\/21505594.2021.1886777.","journal-title":"Virulence"},{"key":"1105_CR34","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.humic.2016.09.002","volume":"4","author":"M Hosny","year":"2017","unstructured":"Hosny M, Cassir N, La Scola B. Updating on gut microbiota and its relationship with the occurrence of necrotizing enterocolitis. Hum Microbiome J. 2017;4:14\u20139. https:\/\/doi.org\/10.1016\/j.humic.2016.09.002.","journal-title":"Hum Microbiome J"},{"issue":"1","key":"1105_CR35","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1128\/iai.65.1.35-41.1997","volume":"65","author":"T Kurita-Ochiai","year":"1997","unstructured":"Kurita-Ochiai T, Fukushima K, Ochiai K. Butyric acid-induced apoptosis of murine thymocytes, splenic T cells, and human jurkat T cells. Infect Immun. 1997;65(1):35\u201341. https:\/\/doi.org\/10.1128\/iai.65.1.35-41.1997.","journal-title":"Infect Immun"},{"key":"1105_CR36","doi-asserted-by":"publisher","unstructured":"Nankova BB, Agarwal R, MacFabe DF, La Gamma EF. Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission, in PC12 cells-possible relevance to autism spectrum disorders. PLoS ONE. 2014;9(8):e103740. https:\/\/doi.org\/10.1371\/journal.pone.0103740.","DOI":"10.1371\/journal.pone.0103740"},{"key":"1105_CR37","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.anifeedsci.2017.07.009","volume":"232","author":"B Song","year":"2017","unstructured":"Song B, Li H, Wu Y, Zhen W, Wang Z, Xia Z, et al. Effect of microencapsulated sodium butyrate dietary supplementation on growth performance and intestinal barrier function of broiler chickens infected with necrotic enteritis. Anim Feed Sci Technol. 2017;232:6\u201315. https:\/\/doi.org\/10.1016\/j.anifeedsci.2017.07.009.","journal-title":"Anim Feed Sci Technol"},{"issue":"4","key":"1105_CR38","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1111\/j.1751-7915.2010.00244.x","volume":"4","author":"V Eeckhaut","year":"2011","unstructured":"Eeckhaut V, Van Immerseel F, Croubels S, De Baere S, Haesebrouck F, Ducatelle R, et al. Butyrate production in phylogenetically diverse Firmicutes isolated from the chicken caecum. Microb Biotechnol. 2011;4(4):503\u201312. https:\/\/doi.org\/10.1111\/j.1751-7915.2010.00244.x.","journal-title":"Microb Biotechnol"},{"issue":"2","key":"1105_CR39","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1111\/j.1574-6968.2002.tb11467.x","volume":"217","author":"SE Pryde","year":"2002","unstructured":"Pryde SE, Duncan SH, Hold GL, Stewart CS, Flint HJ. The microbiology of butyrate formation in the human colon. FEMS Microbiol Lett. 2002;217(2):133\u20139. https:\/\/doi.org\/10.1111\/j.1574-6968.2002.tb11467.x.","journal-title":"FEMS Microbiol Lett"},{"issue":"Pt 12","key":"1105_CR40","doi-asserted-by":"publisher","first-page":"2799","DOI":"10.1099\/ijs.0.65730-0","volume":"58","author":"V Eeckhaut","year":"2008","unstructured":"Eeckhaut V, Van Immerseel F, Teirlynck E, Pasmans F, Fievez V, Snauwaert C, et al. Butyricicoccus pullicaecorum gen. nov., sp. nov., an anaerobic, butyrate-producing bacterium isolated from the caecal content of a broiler chicken. Int J Syst Evol Microbiol. 2008;58(Pt 12):2799\u2013802. https:\/\/doi.org\/10.1099\/ijs.0.65730-0.","journal-title":"Int J Syst Evol Microbiol"},{"key":"1105_CR41","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1186\/s12917-014-0311-7","volume":"10","author":"A Jung","year":"2014","unstructured":"Jung A, Rautenschlein S. Comprehensive report of an Enterococcus cecorum infection in a broiler flock in Northern Germany. BMC Vet Res. 2014;10:311. https:\/\/doi.org\/10.1186\/s12917-014-0311-7.","journal-title":"BMC Vet Res"},{"issue":"5","key":"1105_CR42","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1128\/AEM.03440-13","volume":"80","author":"J Li","year":"2014","unstructured":"Li J, McClane BA. The sialidases of Clostridium perfringens type D strain CN3718 differ in their properties and sensitivities to inhibitors. Appl Environ Microbiol. 2014;80(5):1701\u20139. https:\/\/doi.org\/10.1128\/AEM.03440-13.","journal-title":"Appl Environ Microbiol"},{"key":"1105_CR43","doi-asserted-by":"publisher","unstructured":"McClane BA, Robertson SL, Li J. Clostridium perfringens. In: Doyle MP, Buchanan RL, editors. Food microbiology: fundamentals and frontiers. 4th ed. 2012. p. 465\u201389. https:\/\/doi.org\/10.1128\/9781555818463.ch18.","DOI":"10.1128\/9781555818463.ch18"},{"issue":"12","key":"1105_CR44","doi-asserted-by":"publisher","first-page":"3126","DOI":"10.1007\/s10620-012-2259-4","volume":"57","author":"H-B Wang","year":"2012","unstructured":"Wang H-B, Wang P-Y, Wang X, Wan Y-L, Liu Y-C. Butyrate enhances intestinal epithelial barrier function via up-regulation of tight junction protein Claudin-1 transcription. Dig Dis Sci. 2012;57(12):3126\u201335. https:\/\/doi.org\/10.1007\/s10620-012-2259-4.","journal-title":"Dig Dis Sci"},{"key":"1105_CR45","doi-asserted-by":"publisher","first-page":"w13596","DOI":"10.4414\/smw.2012.13596","volume":"142","author":"P Sossai","year":"2012","unstructured":"Sossai P. Butyric acid: what is the future for this old substance? Swiss Med Wkly. 2012;142:w13596. https:\/\/doi.org\/10.4414\/smw.2012.13596.","journal-title":"Swiss Med Wkly"},{"issue":"2","key":"1105_CR46","doi-asserted-by":"publisher","first-page":"259","DOI":"10.3390\/ani10020259","volume":"10","author":"N Abdelli","year":"2020","unstructured":"Abdelli N, P\u00e9rez JF, Vilarrasa E, Cabeza Luna I, Melo-Duran D, D\u2019Angelo M, et al. Targeted-release organic acids and essential oils improve performance and digestive function in broilers under a necrotic enteritis challenge. Animals (Basel). 2020;10(2):259. https:\/\/doi.org\/10.3390\/ani10020259.","journal-title":"Anim (Basel)"},{"issue":"4","key":"1105_CR47","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1097\/00005176-200210000-00016","volume":"35","author":"J Lin","year":"2002","unstructured":"Lin J, Nafday SM, Chauvin SN, Magid MS, Pabbatireddy S, Holzman IR, et al. Variable effects of short chain fatty acids and lactic acid in inducing intestinal mucosal injury in newborn rats. J Pediatr Gastroenterol Nutr. 2002;35(4):545\u201350. https:\/\/doi.org\/10.1097\/00005176-200210000-00016.","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"14","key":"1105_CR48","doi-asserted-by":"publisher","first-page":"8412","DOI":"10.1073\/pnas.1430846100","volume":"100","author":"H Li","year":"2003","unstructured":"Li H, Myeroff L, Smiraglia D, Romero MF, Pretlow TP, Kasturi L, et al. SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers. Proc Natl Acad Sci U S A. 2003;100(14):8412\u20137. https:\/\/doi.org\/10.1073\/pnas.1430846100.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"1105_CR49","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1080\/03079451003610586","volume":"39","author":"L Timbermont","year":"2010","unstructured":"Timbermont L, Lanckriet A, Dewulf J, Nollet N, Schwarzer K, Haesebrouck F, et al. Control of Clostridium perfringens-induced necrotic enteritis in broilers by target-released butyric acid, fatty acids and essential oils. Avian Pathol. 2010;39(2):117\u201321. https:\/\/doi.org\/10.1080\/03079451003610586.","journal-title":"Avian Pathol"},{"issue":"4","key":"1105_CR50","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1159\/000321614","volume":"155","author":"M Metz","year":"2011","unstructured":"Metz M, Doyle E, Bindslev-Jensen C, Watanabe T, Zuberbier T, Maurer M. Effects of antihistamines on innate immune responses to severe bacterial infection in mice. Int Arch Allergy Immunol. 2011;155(4):355\u201360. https:\/\/doi.org\/10.1159\/000321614.","journal-title":"Int Arch Allergy Immunol"},{"key":"1105_CR51","doi-asserted-by":"publisher","first-page":"895","DOI":"10.3390\/metabo12100895","volume":"12","author":"S Smolinska","year":"2022","unstructured":"Smolinska S, Winiarska E, Globinska A, Jutel M. Histamine: a mediator of intestinal disorders\u2014a review. Metabolites. 2022;12:895. https:\/\/doi.org\/10.3390\/metabo12100895.","journal-title":"Metabolites"},{"issue":"9","key":"1105_CR52","doi-asserted-by":"publisher","first-page":"1774","DOI":"10.3390\/nu14091774","volume":"14","author":"S S\u00e1nchez-P\u00e9rez","year":"2022","unstructured":"S\u00e1nchez-P\u00e9rez S, Comas-Bast\u00e9 O, Duelo A, Veciana-Nogu\u00e9s MT, Berlanga M, Latorre-Moratalla ML, et al. Intestinal dysbiosis in patients with histamine intolerance. Nutrients. 2022;14(9):1774. https:\/\/doi.org\/10.3390\/nu14091774.","journal-title":"Nutrients"},{"key":"1105_CR53","doi-asserted-by":"publisher","DOI":"10.1002\/9781118728291","volume-title":"Clostridial diseases of animals","author":"FA Uzal","year":"2016","unstructured":"Uzal FA, Songer JG, Prescott JF, Popoff MR. Clostridial diseases of animals. Chichester: Wiley; 2016."},{"key":"1105_CR54","doi-asserted-by":"publisher","unstructured":"Kaiser JC, Heinrichs DE. Branching out: alterations in bacterial physiology and virulence due to branched-chain amino acid deprivation. mBio. 2018;9(5):e01188\u201318. https:\/\/doi.org\/10.1128\/mBio.01188-18.","DOI":"10.1128\/mBio.01188-18"},{"issue":"1","key":"1105_CR55","doi-asserted-by":"publisher","first-page":"20","DOI":"10.3109\/10409238.2012.735643","volume":"48","author":"ND Ridgway","year":"2013","unstructured":"Ridgway ND. The role of phosphatidylcholine and choline metabolites to cell proliferation and survival. Crit Rev Biochem Mol Biol. 2013;48(1):20\u201338. https:\/\/doi.org\/10.3109\/10409238.2012.735643.","journal-title":"Crit Rev Biochem Mol Biol"},{"key":"1105_CR56","doi-asserted-by":"publisher","first-page":"839","DOI":"10.3390\/pathogens11080839","volume":"11","author":"G Akerele","year":"2022","unstructured":"Akerele G, Al Hakeem WG, Lourenco J, Selvaraj RK. The effect of necrotic enteritis challenge on production performance, cecal microbiome, and cecal tonsil transcriptome in broilers. Pathogens. 2022;11:839. https:\/\/doi.org\/10.3390\/pathogens11080839.","journal-title":"Pathogens"},{"issue":"9","key":"1105_CR57","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.3945\/jn.109.104638","volume":"139","author":"L Peng","year":"2009","unstructured":"Peng L, Li Z-R, Green RS, Holzmanr IR, Lin J. Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J Nutr. 2009;139(9):1619\u201325. https:\/\/doi.org\/10.3945\/jn.109.104638.","journal-title":"J Nutr"},{"issue":"2","key":"1105_CR58","doi-asserted-by":"publisher","first-page":"e00889","DOI":"10.1128\/mBio.00889-14","volume":"5","author":"M Vital","year":"2014","unstructured":"Vital M, Howe AC, Tiedje JM. Revealing the bacterial butyrate synthesis pathways by analyzing (meta)genomic data. mBio. 2014;5(2):e00889. https:\/\/doi.org\/10.1128\/mBio.00889-14.","journal-title":"mBio"},{"key":"1105_CR59","doi-asserted-by":"publisher","unstructured":"Reeds PJ, Burrin DG, Stoll B, Jahoor F. Intestinal glutamate metabolism. J Nutr. 2000;130(4):978S\u201382S. https:\/\/doi.org\/10.1093\/jn\/130.4.978S.","DOI":"10.1093\/jn\/130.4.978S"},{"issue":"2","key":"1105_CR60","doi-asserted-by":"publisher","first-page":"119","DOI":"10.5114\/pg.2020.95556","volume":"15","author":"T Banasiewicz","year":"2020","unstructured":"Banasiewicz T, Domagalska D, Borycka-Kiciak K, Rydzewska G. Determination of butyric acid dosage based on clinical and experimental studies\u2013a literature review. Prz Gastroenterol. 2020;15(2):119\u201325. https:\/\/doi.org\/10.5114\/pg.2020.95556.","journal-title":"Prz Gastroenterol"},{"key":"1105_CR61","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.3389\/fmicb.2016.01945","volume":"7","author":"S Anand","year":"2016","unstructured":"Anand S, Kaur H, Mande SS. Comparative in silico analysis of butyrate production pathways in gut commensals and pathogens. Front Microbiol. 2016;7:1945. https:\/\/doi.org\/10.3389\/fmicb.2016.01945.","journal-title":"Front Microbiol"},{"key":"1105_CR62","doi-asserted-by":"publisher","first-page":"3928","DOI":"10.1111\/febs.16562","volume":"290","author":"P Chaukimath","year":"2023","unstructured":"Chaukimath P, Frankel G, Visweswariah SS. The metabolic impact of bacterial infection in the gut. FEBS J. 2023;290:3928\u201345. https:\/\/doi.org\/10.1111\/febs.16562.","journal-title":"FEBS J"}],"container-title":["Journal of Animal Science and Biotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40104-024-01105-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40104-024-01105-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40104-024-01105-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,2]],"date-time":"2024-11-02T01:02:04Z","timestamp":1730509324000},"score":1,"resource":{"primary":{"URL":"https:\/\/jasbsci.biomedcentral.com\/articles\/10.1186\/s40104-024-01105-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,2]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["1105"],"URL":"https:\/\/doi.org\/10.1186\/s40104-024-01105-5","relation":{},"ISSN":["2049-1891"],"issn-type":[{"value":"2049-1891","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,2]]},"assertion":[{"value":"27 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 September 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 November 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This work was approved by the University of Saskatchewan\u2019s Animal Research Ethics Board and adhered to the Canadian Council on Animal Care Guidelines for humane use of animal use.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Authors do not have any competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"144"}}