{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:36Z","timestamp":1787028576183,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32402800"],"award-info":[{"award-number":["32402800"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>As a nutritionally important amino acid, cysteine (Cys) could attenuate oxidative damage on growth performance and intestinal barrier function in piglets. However, the mechanism of Cys in attenuating intestinal injury remains unclear. The aim of this study was to investigate the mechanism of Cys in defending against intestinal inflammation in piglets. A total of twenty-four piglets were divided into four groups and fed a diet with or without 0.1% BPA or Cys for a 28 d feeding trial. The results showed that Cys supplementation reinstated the jejunal barrier by increasing cell proliferation and the goblet cell number, and decreased cell apoptosis upon BPA exposure. Cys supplementation also decreased serum and jejunal pro-inflammatory cytokine and immunoglobulin levels in BPA-challenged piglets. Furthermore, Cys mitigated inflammation by normalizing the activation of the toll-like receptor 4 (TLR4)-JNK\/MAPK-nuclear factor-kappa B (NF-\u03baB) pathway caused by BPA. Additionally, dietary Cys supplementation restored the levels of butyrate, valerate and isovalerate in cecum contents that were decreased by BPA exposure. Meanwhile, Cys supplementation normalized the abundances of Prevotellaceae and Romboutsia upon BPA exposure. In conclusion, Cys is critical to nutrition through attenuating intestinal inflammation by regulating gut microbial balance and suppressing the TLR4-JNK\/MAPK-NF-\u03baB pathway.<\/jats:p>","DOI":"10.3390\/ijms262411991","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T15:27:20Z","timestamp":1765553240000},"page":"11991","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cysteine Attenuates Intestinal Inflammation by Regulating the Gut Microbiota and TLR4-JNK\/MAPK-NF-\u03baB Pathway in Piglets"],"prefix":"10.3390","volume":"26","author":[{"given":"Rui","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), College of Animal Science and Technology, Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai\u2019an 271017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengxiang","family":"Qin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), College of Animal Science and Technology, Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai\u2019an 271017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihao","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), College of Animal Science and Technology, Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai\u2019an 271017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), College of Animal Science and Technology, Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai\u2019an 271017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4943-0322","authenticated-orcid":false,"given":"Shuzhen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), College of Animal Science and Technology, Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai\u2019an 271017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7028-6732","authenticated-orcid":false,"given":"Xuejun","family":"Yuan","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiren","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), College of Animal Science and Technology, Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai\u2019an 271017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyun","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5055-2159","authenticated-orcid":false,"given":"Ning","family":"Jiao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), College of Animal Science and Technology, Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai\u2019an 271017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41580-020-0278-0","article-title":"Cell fate specification and differentiation in the adult mammalian intestine","volume":"22","author":"Beumer","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.3945\/jn.112.164947","article-title":"Fish Oil Enhances Intestinal Integrity and Inhibits TLR4 and NOD2 Signaling Pathways in Weaned Pigs after LPS Challenge3","volume":"142","author":"Liu","year":"2012","journal-title":"J. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.aninu.2020.11.008","article-title":"Xylooligosaccharide attenuates lipopolysaccharide-induced intestinal injury in piglets via suppressing inflammation and modulating cecal microbial communities","volume":"7","author":"Wang","year":"2021","journal-title":"Anim. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Li, Y., Zhao, X., Zhang, L., Zhan, X., Liu, Z., Zhuo, Y., Lin, Y., Fang, Z., Che, L., and Feng, B. (2020). Effects of a Diet Supplemented with Exogenous Catalase from Penicillium notatum on Intestinal Development and Microbiota in Weaned Piglets. Microorganisms, 8.","DOI":"10.3390\/microorganisms8030391"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Hashimoto-Hill, S., and Alenghat, T. (2021). Inflammation-Associated Microbiota Composition Across Domestic Animals. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.649599"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"115836","DOI":"10.1016\/j.ecoenv.2023.115836","article-title":"Glutamine attenuates bisphenol A-induced intestinal inflammation by regulating gut microbiota and TLR4-p38\/MAPK-NF-\u03baB pathway in piglets","volume":"270","author":"Liu","year":"2024","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Szymanska, K., Makowska, K., and Gonkowski, S. (2018). The Influence of High and Low Doses of Bisphenol A (BPA) on the Enteric Nervous System of the Porcine Ileum. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030917"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1002\/mnfr.201500031","article-title":"L-Cysteine metabolism and its nutritional implications","volume":"60","author":"Yin","year":"2016","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4093","DOI":"10.2527\/jas.2011-3944","article-title":"First-pass splanchnic metabolism of dietary cysteine in weanling pigs1","volume":"89","author":"Cottrell","year":"2011","journal-title":"J. Anim. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.trsl.2006.12.010","article-title":"Comparative efficacies of 2 cysteine prodrugs and a glutathione delivery agent in a colitis model","volume":"150","author":"Oz","year":"2007","journal-title":"Transl. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2100728","DOI":"10.1002\/mnfr.202100728","article-title":"Cysteine Exerts an Essential Role in Maintaining Intestinal Integrity and Function Independent of Glutathione","volume":"66","author":"Jiao","year":"2022","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Qin, P., Ma, S., Li, C., Di, Y., Liu, Z., Wang, H., Li, Y., Jiang, S., Yang, W., and Jiao, N. (2023). Cysteine Attenuates the Impact of Bisphenol A-Induced Oxidative Damage on Growth Performance and Intestinal Function in Piglets. Toxics, 11.","DOI":"10.3390\/toxics11110902"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1073\/pnas.0907697107","article-title":"Impact of oral bisphenol A at reference doses on intestinal barrier function and sex differences after perinatal exposure in rats","volume":"107","author":"Braniste","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.envpol.2016.08.039","article-title":"Bisphenol A alters gut microbiome: Comparative metagenomics analysis","volume":"218","author":"Lai","year":"2016","journal-title":"Environ. Pollut."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.nut.2017.03.012","article-title":"Maternal methyl donor supplementation during gestation counteracts bisphenol A\u2013induced oxidative stress in sows and offspring","volume":"45","author":"Mou","year":"2018","journal-title":"Nutrition"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"114285","DOI":"10.1016\/j.ecoenv.2022.114285","article-title":"Exposure to bisphenol A induced oxidative stress, cell death and impaired epithelial homeostasis in the adult Drosophila melanogaster midgut","volume":"248","author":"Chen","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1021\/acs.jafc.2c07885","article-title":"Selenomethionine Alleviates DON-Induced Oxidative Stress via Modulating Keap1\/Nrf2 Signaling in the Small Intestinal Epithelium","volume":"71","author":"Zhu","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.bbagen.2009.05.018","article-title":"L-cysteine supplementation attenuates local inflammation and restores gut homeostasis in a porcine model of colitis","volume":"1790","author":"Kim","year":"2009","journal-title":"Biochim. Et Biophys. Acta (BBA)-Gen. Subj."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"111270","DOI":"10.1016\/j.biopha.2021.111270","article-title":"Environmental contaminant BPA causes intestinal damage by disrupting cellular repair and injury homeostasis in vivo and in vitro","volume":"137","author":"Wang","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1177\/1753425916632303","article-title":"L-Cysteine protects intestinal integrity, attenuates intestinal inflammation and oxidant stress, and modulates NF-\u03baB and Nrf2 pathways in weaned piglets after LPS challenge","volume":"22","author":"Song","year":"2016","journal-title":"Innate Immun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1017\/S0007114513001608","article-title":"Effect of N-acetyl cysteine on enterocyte apoptosis and intracellular signalling pathways\u2019 response to oxidative stress in weaned piglets","volume":"110","author":"Zhu","year":"2013","journal-title":"Br. J. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1007\/s00204-019-02425-6","article-title":"Deoxynivalenol inhibits the expression of trefoil factors (TFF) by intestinal human and porcine goblet cells","volume":"93","author":"Graziani","year":"2019","journal-title":"Arch. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4190","DOI":"10.1016\/j.cell.2022.09.024","article-title":"Nociceptor neurons direct goblet cells via a CGRP-RAMP1 axis to drive mucus production and gut barrier protection","volume":"185","author":"Yang","year":"2022","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1016\/0016-5085(95)90708-4","article-title":"Intestinal permeability: An overview","volume":"108","author":"Bjarnason","year":"1995","journal-title":"Gastroenterology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1126\/science.270.5239.1203","article-title":"Inflammatory Bowel Disease and Adenomas in Mice Expressing a Dominant Negative N-Cadherin","volume":"270","author":"Hermiston","year":"1995","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Amoroso, C., Perillo, F., Strati, F., Fantini, M., Caprioli, F., and Facciotti, F. (2020). The Role of Gut Microbiota Biomodulators on Mucosal Immunity and Intestinal Inflammation. Cells, 9.","DOI":"10.3390\/cells9051234"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1146\/annurev-animal-021419-083720","article-title":"The Immunoglobulins: New Insights, Implications, and Applications","volume":"8","author":"Sun","year":"2020","journal-title":"Annu. Rev. Anim. Biosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1186\/s12974-019-1538-9","article-title":"Ciprofloxacin and levofloxacin attenuate microglia inflammatory response via TLR4\/NF-kB pathway","volume":"16","author":"Zusso","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/aps.2015.138","article-title":"A novel synthetic compound MCAP suppresses LPS-induced murine microglial activation in vitro via inhibiting NF-kB and p38 MAPK pathways","volume":"37","author":"Kim","year":"2016","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s00210-010-0527-4","article-title":"Expression of TNF-\u03b1 and IL-6 in HMC-1 cells treated with bisphenol A is attenuated by plant-originating glycoprotein (75 kDa) by blocking p38 MAPK","volume":"382","author":"Lee","year":"2010","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7442","DOI":"10.1096\/fj.201902503R","article-title":"Restoring mitochondrial function and normalizing ROS-JNK\/MAPK pathway exert key roles in glutamine ameliorating bisphenol a-induced intestinal injury","volume":"34","author":"Jiao","year":"2020","journal-title":"FASEB J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.tim.2017.05.004","article-title":"Gut Microbiota Dysbiosis in Postweaning Piglets: Understanding the Keys to Health","volume":"25","author":"Gresse","year":"2017","journal-title":"Trends Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hu, R., Li, S., Diao, H., Huang, C., Yan, J., Wei, X., Zhou, M., He, P., Wang, T., and Fu, H. (2023). The interaction between dietary fiber and gut microbiota, and its effect on pig intestinal health. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1095740"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1997560","DOI":"10.1080\/19490976.2021.1997560","article-title":"Bacteroidota and Lachnospiraceae integration into the gut microbiome at key time points in early life are linked to infant neurodevelopment","volume":"13","author":"Oliphant","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.cell.2011.04.022","article-title":"NLRP6 Inflammasome Regulates Colonic Microbial Ecology and Risk for Colitis","volume":"145","author":"Elinav","year":"2011","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/j.1574-6968.2000.tb09265.x","article-title":"Prevotella enzymes involved in mucin oligosaccharide degradation and evidence for a small operon of genes expressed during growth on mucin","volume":"190","author":"Wright","year":"2000","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e3698","DOI":"10.7717\/peerj.3698","article-title":"Genomic and functional analysis of Romboutsia ilealis CRIBT reveals adaptation to the small intestine","volume":"5","author":"Gerritsen","year":"2017","journal-title":"PeerJ"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"13974","DOI":"10.1038\/s41598-018-32413-2","article-title":"Mucosal microbiota of intestinal polyps reveals putative biomarkers of colorectal cancer","volume":"8","author":"Mangifesta","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Li, H., Ma, L., Li, Z., Yin, J., Tan, B., Chen, J., Jiang, Q., and Ma, X. (2021). Evolution of the Gut Microbiota and Its Fermentation Characteristics of Ningxiang Pigs at the Young Stage. Animals, 11.","DOI":"10.3390\/ani11030638"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.cjche.2019.07.015","article-title":"The relationships among sCOD, VFAs, microbial community, and biogas production during anaerobic digestion of rice straw pretreated with ammonia","volume":"28","author":"Zuo","year":"2020","journal-title":"Chin. J. Chem. Eng."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1136\/gutjnl-2016-313235","article-title":"A microbial signature for Crohn\u2019s disease","volume":"66","author":"Pascal","year":"2017","journal-title":"Gut"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Zhu, L., Li, D., and Yang, X. (2023). Gut metabolomics and 16S rRNA sequencing analysis of the effects of arecoline on non-alcoholic fatty liver disease in rats. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1132026"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"21594","DOI":"10.1021\/acs.jafc.4c04526","article-title":"Branched short-chain fatty acid-rich fermented protein food improves the growth and intestinal health by regulating gut microbiota and metabolites in young pigs","volume":"72","author":"Chi","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1038\/nmeth.2604","article-title":"UPARSE: Highly accurate OTU sequences from microbial amplicon reads","volume":"10","author":"Edgar","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jbiotec.2017.06.1198","article-title":"25 years of serving the community with ribosomal RNA gene reference databases and tools","volume":"261","author":"Yilmaz","year":"2017","journal-title":"J. Biotechnol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/11991\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T08:48:39Z","timestamp":1765874919000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/11991"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,12]]},"references-count":45,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262411991"],"URL":"https:\/\/doi.org\/10.3390\/ijms262411991","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,12]]}}}