{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:20:29Z","timestamp":1787242829345,"version":"build-2736575974"},"reference-count":61,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["82273626"],"award-info":[{"award-number":["82273626"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["ZR2024MH073"],"award-info":[{"award-number":["ZR2024MH073"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Key technology research and industrialization demonstration projects in Qingdao City","award":["25-1-1-gjgg-71-nsh"],"award-info":[{"award-number":["25-1-1-gjgg-71-nsh"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Objectives: This study is intended to reveal whether the boost in immune function in immunocompromised mice from niacin supplementation is connected to the upkeep of intestinal homeostasis and the modulation of the hydroxycarboxylic acid receptor 2 (HCAR2)\/NOD-like receptor protein 3 (NLRP3) and prostaglandin endoperoxide synthase 2 (PTGS2)\/prostaglandin E2 (PGE2) signaling pathways. Methods: Balb\/c mice were employed in this study as a model for immunosuppression caused by cyclophosphamide (CTX) injection. Results: The study showed that niacin supplementation restored spleen and liver indices, enhanced cytokine secretion, and increased Th1\/Th2 cytokine levels. Niacin effectively enhanced the phagocytic index, natural killer cell (NK cell) activity, splenic lymphocyte activity and delayed-type hypersensitivity (DTH) reaction in immunocompromised mice. Histopathological examination showed that niacin intervention alleviated injury in mice ilea. Intestinal barrier tight junction proteins were expressed at much higher levels, while the serum concentrations of diamine oxidase (DAO) and fatty acid-binding protein 2 (FABP2) were markedly lowered. Furthermore, the expression of the intestinal HCAR2\/NLRP3 signaling pathway and subsequent inflammatory mediators was significantly elevated after niacin administration compared with the CTX group. Niacin supplementation improved the composition of the gut microbiota, increasing the Firmicutes\/Bacteroidetes (F\/B) ratio. Spearman correlation analysis showed significant correlations between cytokine-related indices and several gut microbiotas. Within a network pharmacology framework including target screening, network construction and molecular docking, PTGS2 emerged as a candidate target of niacin, suggesting its role in counteracting immunosuppression. Further experimental findings showed that niacin markedly decreased the protein expression of PTGS2 and the levels of its downstream mediators PGE2, E-prostanoid receptor type 2 (EP2) and (E-prostanoid receptor type 4 (EP4) in the ileal tissue of mice treated with CTX. Conclusions: In conclusion, niacin supplementation alleviated CTX-induced immunosuppression by maintaining intestinal homeostasis and regulating the intestinal HCAR2\/NLRP3 and PTGS2\/PGE2\/EP2-EP4 pathways.<\/jats:p>","DOI":"10.3390\/nu18050744","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T13:58:03Z","timestamp":1772114283000},"page":"744","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Niacin Mitigates Cyclophosphamide-Induced Immunosuppression by Maintaining Intestinal Homeostasis and Regulating the HCAR2\/NLRP3 and PTGS2\/PGE2 Signaling Pathways"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0852-5289","authenticated-orcid":false,"given":"Yixian","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Zhou","sequence":"additional","affiliation":[{"name":"The First Clinical College, Ningxia Medical University, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guifa","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medicine, Qingdao Medical College, Qingdao University, 308 Ningxia Road, Qingdao 266021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanzheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongtong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kening","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0675-6963","authenticated-orcid":false,"given":"Hui","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1126\/science.1240537","article-title":"The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide","volume":"342","author":"Viaud","year":"2013","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"145273","DOI":"10.1016\/j.ijbiomac.2025.145273","article-title":"Oyster polysaccharides alleviate cyclophosphamide-induced immunosuppression in mice by modulating lymphocytes profile and maintaining intestinal homeostasis","volume":"319","author":"Jia","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.ejphar.2013.06.006","article-title":"The changes induced by cyclophosphamide in intestinal barrier and microflora in mice","volume":"714","author":"Yang","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1039\/D2FO03769F","article-title":"Ameliorating effects of Hericium erinaceus polysaccharides on intestinal barrier injury in immunocompromised mice induced by cyclophosphamide","volume":"14","author":"Tian","year":"2023","journal-title":"Food Funct."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e00080-20","DOI":"10.1128\/mSystems.00080-20","article-title":"Cyclophosphamide Increases Lactobacillus in the Intestinal Microbiota in Chickens","volume":"5","author":"Mesa","year":"2020","journal-title":"mSystems"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Meng, Y., Wang, J., Wang, Z., Li, X., Zhang, Y., and Liu, H. (2019). Lactobacillus plantarum KLDS1.0318 Ameliorates Impaired Intestinal Immunity and Metabolic Disorders in Cyclophosphamide-Treated Mice. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.00731"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s12602-022-10015-9","article-title":"Lactiplantibacillus plantarum DLPT4 Protects Against Cyclophosphamide-Induced Immunosuppression in Mice by Regulating Immune Response and Intestinal Flora","volume":"16","author":"Song","year":"2024","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"143692","DOI":"10.1016\/j.ijbiomac.2025.143692","article-title":"Rehmannia glutinosa polysaccharides alleviate cyclophosphamide-induced immunosuppression by enhancing immunity and restoring intestinal homeostasis","volume":"311","author":"Yu","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"133768","DOI":"10.1016\/j.foodchem.2022.133768","article-title":"Purple red rice anthocyanins alleviate intestinal damage in cyclophosphamide-induced mice associated with modulation of intestinal barrier function and gut microbiota","volume":"397","author":"Chen","year":"2022","journal-title":"Food Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1002\/jsfa.11458","article-title":"Resveratrol regulates intestinal barrier function in cyclophosphamide-induced immunosuppressed mice","volume":"102","author":"Song","year":"2022","journal-title":"J. Sci. Food Agric."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1097\/CCM.0b013e3181feeae4","article-title":"Niacin attenuates lung inflammation and improves survival during sepsis by downregulating the nuclear factor-\u03baB pathway","volume":"39","author":"Kwon","year":"2011","journal-title":"Crit. Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"101718","DOI":"10.1016\/j.xcrm.2024.101718","article-title":"Dietary vitamin B3 supplementation induces the antitumor immunity against liver cancer via biased GPR109A signaling in myeloid cell","volume":"5","author":"Yang","year":"2024","journal-title":"Cell Rep. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/s41392-020-00311-7","article-title":"NAD+ metabolism: Pathophysiologic mechanisms and therapeutic potential","volume":"5","author":"Xie","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"101195","DOI":"10.1016\/j.molmet.2021.101195","article-title":"Role of NAD+ in regulating cellular and metabolic signaling pathways","volume":"49","author":"Amjad","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1124\/jpet.107.120758","article-title":"NAD+ and vitamin B3: From metabolism to therapies","volume":"324","author":"Sauve","year":"2008","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"107584","DOI":"10.1016\/j.intimp.2021.107584","article-title":"Effects of niacin on intestinal immunity, microbial community and intestinal barrier in weaned piglets during starvation","volume":"95","author":"Feng","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.2174\/138161208786264188","article-title":"Zinc, metallothioneins and longevity: Interrelationships with niacin and selenium","volume":"14","author":"Mocchegiani","year":"2008","journal-title":"Curr. Pharm. Des."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"109054","DOI":"10.1016\/j.intimp.2022.109054","article-title":"Effects of niacin on intestinal epithelial Barrier, intestinal Immunity, and microbial community in weaned piglets challenged by PDCoV","volume":"111","author":"Chen","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.fsi.2015.12.015","article-title":"Deficiency of dietary niacin impaired intestinal mucosal immune function via regulating intestinal NF-\u03baB, Nrf2 and MLCK signaling pathways in young grass carp (Ctenopharyngodon idella)","volume":"49","author":"Feng","year":"2016","journal-title":"Fish. Shellfish Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.immuni.2013.12.007","article-title":"Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis","volume":"40","author":"Singh","year":"2014","journal-title":"Immunity"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"122004","DOI":"10.1016\/j.lfs.2023.122004","article-title":"Niacin modulates depressive-like behavior in experimental colitis through GPR109A-dependent mechanisms","volume":"330","author":"Wadie","year":"2023","journal-title":"Life Sci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Liu, S., Qiu, Y., Gu, F., Zhu, X., Zhang, L., and Wang, H. (2022). Niacin Improves Intestinal Health through Up-Regulation of AQPs Expression Induced by GPR109A. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158332"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Liang, X., Shan, T., Zheng, X., Li, J., Zhang, Y., and Wang, H. (2024). Study on the Regulatory Mechanism of Niacin Combined with B. animalis F1-7 in Alleviating Alcoholic Fatty Liver Disease by Up-Regulating GPR109A. Nutrients, 16.","DOI":"10.3390\/nu16234170"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"117394","DOI":"10.1016\/j.biopha.2024.117394","article-title":"Cordycepin mitigates dextran sulfate sodium-induced colitis through improving gut microbiota composition and modulating Th1\/Th2 and Th17\/Treg balance","volume":"180","author":"Liu","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zhang, H., Wang, Y., Zhang, X., Li, J., Zhang, Y., and Wang, H. (2023). Maternal Folic Acid Supplementation during Pregnancy Prevents Hepatic Steatosis in Male Offspring of Rat Dams Fed High-Fat Diet, Which Is Associated with the Regulation of Gut Microbiota. Nutrients, 15.","DOI":"10.3390\/nu15224726"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e2405346","DOI":"10.1002\/advs.202405346","article-title":"Th1\/Th2 Imbalance in Peripheral Blood Echoes Microglia State Dynamics in CNS During TLE Progression","volume":"11","author":"Wang","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/nrclinonc.2009.146","article-title":"Cyclophosphamide and cancer: Golden anniversary","volume":"6","author":"Emadi","year":"2009","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Chen, X., Sun, W., Xu, B., Li, J., Zhang, Y., and Wang, H. (2021). Polysaccharides from the Roots of Millettia Speciosa Champ Modulate Gut Health and Ameliorate Cyclophosphamide-Induced Intestinal Injury and Immunosuppression. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.766296"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1039\/C8FO02312C","article-title":"Ovotransferrin ameliorates the dysbiosis of immunomodulatory function and intestinal microbiota induced by cyclophosphamide","volume":"10","author":"Zhu","year":"2019","journal-title":"Food Funct."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"109793","DOI":"10.1016\/j.foodres.2020.109793","article-title":"Bacillus coagulans 13002 and fructo-oligosaccharides improve the immunity of mice with immunosuppression induced by cyclophosphamide through modulating intestinal-derived and fecal microbiota","volume":"140","author":"Zhao","year":"2021","journal-title":"Food Res. Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1007\/BF00404341","article-title":"Analysis of cytokine mRNA expression in syngeneic islet grafts of NOD mice: Interleukin 2 and interferon gamma mRNA expression correlate with graft rejection and interleukin 10 with graft survival","volume":"37","author":"Rabinovitch","year":"1994","journal-title":"Diabetologia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1097\/TA.0000000000000761","article-title":"The therapeutic effect and mechanism of niacin on acute lung injury in a rat model of hemorrhagic shock: Down-regulation of the reactive oxygen species-dependent nuclear factor \u03baB pathway","volume":"79","author":"Jeong","year":"2015","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.intimp.2014.07.006","article-title":"Niacin attenuates the production of pro-inflammatory cytokines in LPS-induced mouse alveolar macrophages by HCA2 dependent mechanisms","volume":"23","author":"Zhou","year":"2014","journal-title":"Int. Immunopharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1016\/j.clnu.2023.08.017","article-title":"Immediate-release niacin and a monounsaturated fatty acid-rich meal on postprandial inflammation and monocyte characteristics in men with metabolic syndrome","volume":"42","author":"Lopez","year":"2023","journal-title":"Clin. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1007\/s13311-023-01376-2","article-title":"The Promise of Niacin in Neurology","volume":"20","author":"Wuerch","year":"2023","journal-title":"Neurotherapeutics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1172\/JCI36806","article-title":"beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice","volume":"119","author":"Walters","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6734","DOI":"10.1038\/ncomms7734","article-title":"Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome","volume":"6","author":"Macia","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3714","DOI":"10.1002\/1521-4141(200112)31:12<3714::AID-IMMU3714>3.0.CO;2-1","article-title":"PUMA-G, an IFN-gamma-inducible gene in macrophages is a novel member of the seven transmembrane spanning receptor superfamily","volume":"31","author":"Schaub","year":"2001","journal-title":"Eur. J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"115762","DOI":"10.1016\/j.bcp.2023.115762","article-title":"Nicotinic acid attenuates experimental non-alcoholic steatohepatitis by inhibiting the NLRP3 inflammasome\/pyroptosis pathway","volume":"216","year":"2023","journal-title":"Biochem. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"110583","DOI":"10.1016\/j.pnpbp.2022.110583","article-title":"Niacin mitigates blood-brain barrier tight junctional proteins dysregulation and cerebral inflammation in ketamine rat model of psychosis: Role of GPR109A receptor","volume":"119","author":"Ibrahim","year":"2022","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.it.2018.04.002","article-title":"The Intestinal Epithelium: Central Coordinator of Mucosal Immunity","volume":"39","author":"Allaire","year":"2018","journal-title":"Trends Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ali, F., Li, D., Su, Y., Wang, L., Zhang, Y., and Li, J. (2025). Bio-Active Peptides from Marine Sources: Mechanistic Insights into Immune Regulation, Microbiota Modulation, and Intestinal Barrier Protection. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262110508"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Cohen, R.H., Colgan, S.P., and Cartwright, I.M. (2025). Pleiotropic Mucosal Innate Immune Memory in the Gastrointestinal Tract. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262010093"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1136\/gutjnl-2017-314759","article-title":"Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression","volume":"67","author":"Stevens","year":"2018","journal-title":"Gut"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"125953","DOI":"10.1016\/j.ijbiomac.2023.125953","article-title":"Poria cocos polysaccharide improves intestinal barrier function and maintains intestinal homeostasis in mice","volume":"249","author":"Duan","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Liu, S., Zhu, X., Qiu, Y., Gu, F., Zhang, L., and Wang, H. (2021). Effect of Niacin on Growth Performance, Intestinal Morphology, Mucosal Immunity and Microbiota Composition in Weaned Piglets. Animals, 11.","DOI":"10.3390\/ani11082186"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1016\/j.cell.2015.10.072","article-title":"Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis","volume":"163","author":"Nowarski","year":"2015","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/mi.2013.94","article-title":"Nlrp3 activation in the intestinal epithelium protects against a mucosal pathogen","volume":"7","author":"Srinivasan","year":"2014","journal-title":"Mucosal Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s00281-014-0451-7","article-title":"Inflammasomes and the microbiota--partners in the preservation of mucosal homeostasis","volume":"37","author":"Levy","year":"2015","journal-title":"Semin. Immunopathol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.cell.2019.12.016","article-title":"Enteric Nervous System-Derived IL-18 Orchestrates Mucosal Barrier Immunity","volume":"180","author":"Jarret","year":"2020","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1146\/annurev-immunol-070119-115104","article-title":"Interaction Between the Microbiota, Epithelia, and Immune Cells in the Intestine","volume":"38","author":"Kayama","year":"2020","journal-title":"Annu. Rev. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Zhou, B., Yuan, Y., Zhang, S., Li, J., Zhang, Y., and Wang, H. (2020). Intestinal Flora and Disease Mutually Shape the Regional Immune System in the Intestinal Tract. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00575"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Zhou, H., Yan, J., Zhou, K., Li, J., Zhang, Y., and Wang, H. (2024). Effects of Huangqi Gancao Decoction on intestinal immunity and microbiota in immunocompromised mice models. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1390170"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Zhu, X., Zhang, L., Ni, X., Li, J., Zhang, Y., and Wang, H. (2025). Flavonoid Extract of Senecio scandens Buch.-Ham. Ameliorates CTX-Induced Immunosuppression and Intestinal Damage via Activating the MyD88-Mediated Nuclear Factor-\u03baB Signaling Pathway. Nutrients, 17.","DOI":"10.3390\/nu17152540"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"113170","DOI":"10.3748\/wjg.v31.i42.113170","article-title":"Research progress concerning the involvement of the intestinal microbiota in the occurrence and development of inflammatory bowel disease","volume":"31","author":"Zheng","year":"2025","journal-title":"World J. Gastroenterol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12974-016-0780-7","article-title":"Differential expression of E-type prostanoid receptors 2 and 4 in microglia stimulated with lipopolysaccharide","volume":"14","author":"Planas","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Akbari, B., Soltantoyeh, T., Shahosseini, Z., Ghiassi, M., Arefanian, S., and Abedpour, S. (2023). PGE2-EP2\/EP4 signaling elicits mesoCAR T cell immunosuppression in pancreatic cancer. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1209572"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/nm.1968","article-title":"Prostaglandin E2-EP4 signaling promotes immune inflammation through Th1 cell differentiation and Th17 cell expansion","volume":"15","author":"Esaki","year":"2009","journal-title":"Nat. Med."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Thumkeo, D., Punyawatthananukool, S., and Narumiya, S. (2022). Inhibition of PGE2-EP2\/EP4 signalingelicits anti-tumorimmunity through the suppression of mregDC-Treg axis ininflammatory tumor microenvironment. Proc. Annu. Meet. Jpn. Pharmacol. Soc., 96.","DOI":"10.1254\/jpssuppl.96.0_1-B-S04-3"},{"key":"ref_60","first-page":"37","article-title":"Attenuation of niacin-induced prostaglandin D (2) generation by omega-3 fatty acids in THP-1 macrophages and Langerhans dendritic cells","volume":"5","author":"Vanhorn","year":"2012","journal-title":"J. Inflamm. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1038\/srep02973","article-title":"Prostaglandin E2 is critical for the development of niacin-deficiency-induced photosensitivity via ROS production","volume":"3","author":"Sugita","year":"2013","journal-title":"Sci. Rep."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/5\/744\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T05:19:50Z","timestamp":1772255990000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/5\/744"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,26]]},"references-count":61,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["nu18050744"],"URL":"https:\/\/doi.org\/10.3390\/nu18050744","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,26]]}}}