{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:51:49Z","timestamp":1791823909775,"version":"4.3.4"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32473035, 32302755"],"award-info":[{"award-number":["32473035, 32302755"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"crossref","award":["2025JJ40027"],"award-info":[{"award-number":["2025JJ40027"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515011521"],"award-info":[{"award-number":["2024A1515011521"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and technology project in Guangzhou","award":["2025A04J0781"],"award-info":[{"award-number":["2025A04J0781"]}]},{"name":"Special fund for the promotion of breeding industry in the 2024 guangdong provincial rural retitalization strategy","award":["2024-XPY-00-006"],"award-info":[{"award-number":["2024-XPY-00-006"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,12,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Salmonella Enteritidis<\/jats:italic>\n                      infection has caused substantial economic losses in the poultry industry. Traditional antibiotic treatments have led to issues, such as drug-resistant bacteria and antibiotic residues, which pose significant threats to human and animal health, as well as food and environmental safety. Therefore, establishing new, effective prevention and control methods is of paramount importance. In this study, we utilized gas chromatography-mass spectrometry (GC-MS) metabolomics to analyze the metabolomic profiles of chickens infected with varying concentrations of\n                      <jats:italic toggle=\"yes\">Salmonella Enteritidis<\/jats:italic>\n                      . Significant differences in the metabolomes were observed, with citrulline identified as a candidate biomarker, showing increased levels corresponding to higher infection doses. Exogenous addition of citrulline was found to upregulate the expression of the inducible nitric oxide synthase (iNOS) gene in the urea cycle of chicken HD11 macrophages, leading to increased nitric oxide (NO) levels and enhanced phagocytosis of\n                      <jats:italic toggle=\"yes\">Salmonella Enteritidis<\/jats:italic>\n                      by HD11 cells. Furthermore,\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      challenge experiments demonstrated that exogenous citrulline improved the ability of chickens to clear\n                      <jats:italic toggle=\"yes\">Salmonella Enteritidis<\/jats:italic>\n                      and increased their survival rate post-infection. Importantly, this effect could be attenuated by the iNOS inhibitor 1400W. Thus, our study presents a novel strategy for combating bacterial infections through metabolic modulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Chickens respond to\n                      <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n                      infection by adjusting the metabolic state of their bodies. Citrulline can enhance the phagocytic ability of phagocytes by strengthening the urea cycle.\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      clinical trials have revealed that citrulline can increase the survival rate of chickens after\n                      <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n                      infection.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01546-25","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T14:00:42Z","timestamp":1762869642000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Citrulline-enhanced chicken resistance to\n                    <i>Salmonella Enteritidis<\/i>\n                    infection via urea cycle modulation and nitric oxide production"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8935-3886","authenticated-orcid":true,"given":"Ming","family":"Jiang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Key Laboratory of Animal Breeding and Nutrition, Institute of Animal Science, Guangdong Academy of Agricultural Sciences","place":["Guangzhou, China"]},{"id":[{"id":"https:\/\/ror.org\/053w1zy07","id-type":"ROR","asserted-by":"publisher"}],"name":"College of Life Sciences, Hunan Normal University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0531-5580","authenticated-orcid":false,"given":"Pei-pei","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Key Laboratory of Animal Breeding and Nutrition, Institute of Animal Science, Guangdong Academy of Agricultural Sciences","place":["Guangzhou, China"]},{"id":[{"id":"https:\/\/ror.org\/05v9jqt67","id-type":"ROR","asserted-by":"publisher"}],"name":"College of Veterinary medicine, South China Agricultural University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-min","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Key Laboratory of Animal Breeding and Nutrition, Institute of Animal Science, Guangdong Academy of Agricultural Sciences","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Key Laboratory of Animal Breeding and Nutrition, Institute of Animal Science, Guangdong Academy of Agricultural Sciences","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Key Laboratory of Animal Breeding and Nutrition, Institute of Animal Science, Guangdong Academy of Agricultural Sciences","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man-shan","family":"Cai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Key Laboratory of Animal Breeding and Nutrition, Institute of Animal Science, Guangdong Academy of Agricultural Sciences","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chu-xiao","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Key Laboratory of Animal Breeding and Nutrition, Institute of Animal Science, Guangdong Academy of Agricultural Sciences","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-lin","family":"Xie","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Key Laboratory of Animal Breeding and Nutrition, Institute of Animal Science, Guangdong Academy of Agricultural Sciences","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-min","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05v9jqt67","id-type":"ROR","asserted-by":"publisher"}],"name":"College of Veterinary medicine, South China Agricultural University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1175-7730","authenticated-orcid":true,"given":"Jian","family":"Ji","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Key Laboratory of Animal Breeding and Nutrition, Institute of Animal Science, Guangdong Academy of Agricultural Sciences","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25319-7"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-021-00632-6"},{"key":"e_1_3_4_4_2","first-page":"12","volume-title":"Current topics in Salmonella and salmonellosis","author":"Niki M","year":"2017","unstructured":"Niki M, Shakeel A, Zahid K, Koutoulis KC. 2017. Prevalence, risks and antibiotic resistance of Salmonella in poultry production chain, p 12. In MihaiM (ed), Current topics in Salmonella and salmonellosis. IntechOpen, Rijeka."},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms11112814"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.onehlt.2022.100469"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.24655"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare11131946"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/794143"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-022-00840-x"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2023.10.001"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-019-0281-8"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2014.06.008"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010796"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201949561"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/1751-7915.13582"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008188"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21155291"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00278.xB2"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-0199-4"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1159\/000516780"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/metabo10110429"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01452-1"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics13010076"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2021.1988251"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.3390\/ani11123554"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abj0716"},{"key":"e_1_3_4_28_2","first-page":"6","volume-title":"Physiology and pathology of immunology","author":"Jos\u00e9 LMC","year":"2017","unstructured":"Jos\u00e9 LMC, Flor PCG, Oscar GC, Mar\u00eda AMG, JuanFCC. 2017. Physiology and pathology of innate immune response against pathogens, p 6. In Nima R (ed), Physiology and pathology of immunology. IntechOpen, Rijeka."},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19010092"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00191"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11986"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2006.03.005"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22189879"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-11870-3_14"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0414-4"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1001-907"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-54090-0_8"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/21.supplement_2.s162"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.4161\/viru.20328"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1039\/c3tb21259a"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40104-020-00507-5"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00533"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00791-9"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells10071823"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.01546-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.01546-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T14:08:59Z","timestamp":1764684539000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.01546-25"}},"subtitle":[],"editor":[{"given":"Sadjia","family":"Bekal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,12,2]]},"references-count":43,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12,2]]}},"alternative-id":["10.1128\/spectrum.01546-25"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.01546-25","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,2]]},"assertion":[{"value":"2025-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01546-25"}}