{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:28:02Z","timestamp":1792013282961,"version":"4.4.0"},"reference-count":101,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014718","name":"Innovative Research Group Project of the National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014718","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Necrotizing enterocolitis (NEC) is one of the most severe intestinal diseases affecting preterm infants, characterized by high mortality rates and significant long-term complications, which present substantial challenges to clinical management. The primary pathological mechanism underlying NEC is the immature development of the intestinal barrier in preterm infants, which fails to adequately resist luminal pathogen invasion, triggering uncontrolled inflammatory responses and tissue damage. Additionally, intestinal dysbiosis further compromises the integrity of the intestinal barrier. In recent years, growing attention has been given to the role of tryptophan metabolites in maintaining intestinal barrier integrity. As an essential amino acid, tryptophan metabolites\u2014particularly those derived from gut microbiota, such as indole compounds\u2014have been shown to exert significant barrier-protective effects through multiple mechanisms, including the activation of the aryl hydrocarbon receptor (AhR), upregulation of tight junction protein expression, inhibition of inflammatory responses, and promotion of epithelial cell repair. This review aims to summarize the major biological pathways of tryptophan metabolism, with particular emphasis on the molecular mechanisms by which microbial indole derivatives enhance the physical, chemical, and immune barriers. By synthesizing both preclinical studies and clinical evidence, this article explores the translational potential of tryptophan metabolite-targeted strategies for NEC prevention, providing a theoretical foundation for the development of precise preventive interventions.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1782006","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T05:47:43Z","timestamp":1776059263000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Mechanisms by which tryptophan metabolites enhance intestinal barrier function to prevent necrotizing enterocolitis in preterm infants"],"prefix":"10.3389","volume":"17","author":[{"given":"Xinxin","family":"Cui","sequence":"first","affiliation":[{"name":"Pediatric Hospital, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Pediatric Medical College, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianli","family":"Qiu","sequence":"additional","affiliation":[{"name":"Pediatric Hospital, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Pediatric Medical College, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"Pediatric Hospital, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Pediatric Medical College, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Guan","sequence":"additional","affiliation":[{"name":"Pediatric Hospital, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Pediatric Medical College, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Ding","sequence":"additional","affiliation":[{"name":"Pediatric Hospital, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Pediatric Medical College, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suping","family":"Yu","sequence":"additional","affiliation":[{"name":"Pediatric Hospital, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Pediatric Medical College, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhua","family":"Fan","sequence":"additional","affiliation":[{"name":"Pediatric Hospital, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Pediatric Medical College, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guihua","family":"Song","sequence":"additional","affiliation":[{"name":"Pediatric Hospital, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Pediatric Medical College, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianqing","family":"Ren","sequence":"additional","affiliation":[{"name":"Pediatric Hospital, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Pediatric Medical College, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1005408","article-title":"Necrotizing enterocolitis","volume":"364","author":"Neu","year":"2011","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1038\/nrgastro.2016.119","article-title":"Necrotizing enterocolitis: new insights into pathogenesis and mechanisms","volume":"13","author":"Ni\u00f1o","year":"2016","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2009.02.013","article-title":"Mortality of necrotizing enterocolitis expressed by birth weight categories","volume":"44","author":"Fitzgibbons","year":"2009","journal-title":"J Pediatr Surg"},{"key":"B4","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.jpeds.2019.11.011","article-title":"Contemporary outcomes for infants with necrotizing enterocolitis-a systematic review","volume":"220","author":"Jones","year":"2020","journal-title":"J Pediatr"},{"key":"B5","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.jpedsurg.2018.06.012","article-title":"New insights into necrotizing enterocolitis: from laboratory observation to personalized prevention and treatment","volume":"54","author":"Hackam","year":"2019","journal-title":"J Pediatr Surg"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2025.2551117","article-title":"Review: microbial metabolites - a key to address gut inflammation and barrier dysfunction in the premature infant","volume":"17","author":"Robertson","year":"2025","journal-title":"Gut Microbes"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-026-04779-x","article-title":"Identification of key mitochondria-related genes in necrotizing enterocolitis using single-cell hdWGCNA and experimental verification","author":"Chen","year":"2026","journal-title":"Pediatr Res"},{"key":"B8","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1186\/s12964-025-02454-y","article-title":"Indole-3-lactic acid protects the gut vascular barrier following intestinal ischemia injury through AhR\/Nrf2\/STAT3 mediated claudin 2 downregulation","volume":"23","author":"Jia","year":"2025","journal-title":"Cell Commun Signal"},{"key":"B9","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s12981-026-00846-9","article-title":"Quercetin ameliorates HIV-1 gp120 protein-induced intestinal barrier dysfunction by inhibiting the activation of the ERK1\/2 signaling pathway in a Caco-2 cell model","volume":"23","author":"Zhu","year":"2026","journal-title":"AIDS Res Ther"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2025.106401","article-title":"Gut microbiota as a risk and protective factor in neonatal necrotizing enterocolitis: an integrative review","volume":"211","author":"Onofre","year":"2025","journal-title":"Early Hum Dev"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.4014\/jmb.2508.08033","article-title":"Dynamic interactions between the gut microbiome, health, and metabolic disorders in preterm infants","volume":"35","author":"Jang","year":"2025","journal-title":"J Microbiol Biotechnol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2025.2541031","article-title":"Longitudinal analysis of fecal tryptophan metabolites and microbiome composition in very preterm infants: impact of birth mode and feeding type","volume":"17","author":"Wieser","year":"2025","journal-title":"Gut Microbes"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.08.003","article-title":"Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22","volume":"39","author":"Zelante","year":"2013","journal-title":"Immunity"},{"key":"B14","doi-asserted-by":"publisher","first-page":"3294","DOI":"10.1038\/s41467-018-05470-4","article-title":"Microbial tryptophan catabolites in health and disease","volume":"9","author":"Roager","year":"2018","journal-title":"Nat Commun"},{"key":"B15","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1186\/s12866-020-02023-y","article-title":"Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells","volume":"20","author":"Ehrlich","year":"2020","journal-title":"BMC Microbiol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"189","DOI":"10.3892\/mmr.2024.13313","article-title":"Indole-3-propionic acid alleviates intestinal epithelial cell injury via regulation of the TLR4\/NF-\u03baB pathway to improve intestinal barrier function","volume":"30","author":"Chen","year":"2024","journal-title":"Mol Med Rep"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3390\/nu16101531","article-title":"Exploring the immunomodulatory potential of human milk: aryl hydrocarbon receptor activation and its impact on neonatal gut health","volume":"16","author":"Wieser","year":"2024","journal-title":"Nutrients"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-024-03440-9","article-title":"The impact of breastfeeding on the preterm infant's microbiome and metabolome: a pilot study","volume":"97","author":"Schulkers Escalante","year":"2025","journal-title":"Pediatr Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2022-327337","article-title":"Rewiring the altered tryptophan metabolism as a novel therapeutic strategy in inflammatory bowel diseases","volume":"72","author":"Michaudel","year":"2023","journal-title":"Gut"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0237182","article-title":"Maternal administration of probiotics promotes gut development in mouse offsprings","volume":"15","author":"Yu","year":"2020","journal-title":"PloS One"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03316-w","article-title":"Preterm neonatal immunology at the intestinal interface","volume":"77","author":"Van Belkum","year":"2020","journal-title":"Cell Mol Life Sci"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1016\/j.cell.2018.06.045","article-title":"Stereotypic immune system development in newborn children","volume":"174","author":"Olin","year":"2018","journal-title":"Cell"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2018.1506760","article-title":"Changes of intestinal microbiota in early life","volume":"33","author":"Ficara","year":"2020","journal-title":"J Matern Fetal Neonatal Med"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1099\/acmi.0.001077.v3","article-title":"Gut microbiota composition in preterm infants with and without necrotizing enterocolitis: a systematic review and narrative synthesis","volume":"7","author":"Sadeghpour Heravi","year":"2025","journal-title":"Access Microbiol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/nutrit\/nuaf127","article-title":"Tryptophan metabolism in developmental origins of health and disease","volume":"84","author":"de Souza","year":"2026","journal-title":"Nutr Rev"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1177\/11786469251372339","article-title":"Molecular insights into the interaction of tryptophan metabolites with tryptophan and indoleamine 2,3-dioxygenases: nitric oxide a new effector of tryptophan 2,3-dioxygenase and their roles in infection","volume":"18","author":"Badawy","year":"2025","journal-title":"Int J Tryptophan Res"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-022-00484-9","article-title":"Quinolinic acid impairs redox homeostasis, bioenergetic, and cell signaling in rat striatum slices: prevention by coenzyme Q(10)","volume":"40","author":"Ferreira","year":"2022","journal-title":"Neurotox Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00673","article-title":"Cancer immunotherapy by targeting IDO1\/TDO and their downstream effectors","volume":"5","author":"Platten","year":"2014","journal-title":"Front Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2025.103579","article-title":"The tryptophan metabolite 3-hydroxyanthranilic acid alleviates hyperoxia-induced bronchopulmonary dysplasia via inhibiting ferroptosis","volume":"82","author":"Ruan","year":"2025","journal-title":"Redox Biol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1186\/s12964-025-02393-8","article-title":"Interactions between gut microbiota and parkinson's disease: the role of tryptophan metabolism","volume":"23","author":"Fan","year":"2025","journal-title":"Cell Commun Signal"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2018.03.004","article-title":"Peripheral serotonin synthesis as a new drug target","volume":"39","author":"Matthes","year":"2018","journal-title":"Trends Pharmacol Sci"},{"key":"B32","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.phrs.2018.08.005","article-title":"Serotonin, hematopoiesis and stem cells","volume":"140","author":"Fouquet","year":"2019","journal-title":"Pharmacol Res"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1039\/d2fo01900k","article-title":"Lactobacillus rhamnosus GG supernatant promotes intestinal mucin production through regulating 5-HT4R and gut microbiota","volume":"13","author":"Gu","year":"2022","journal-title":"Food Funct"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26094021","article-title":"Restraint stress disrupted intestinal homeostasis via 5-HT\/HTR7\/Wnt\/\u03b2-catenin\/NF-kB signaling","volume":"26","author":"Yu","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.05.003","article-title":"Gut microbiota regulation of tryptophan metabolism in health and disease","volume":"23","author":"Agus","year":"2018","journal-title":"Cell Host Microbe"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032713-120245","article-title":"The aryl hydrocarbon receptor: multitasking in the immune system","volume":"32","author":"Stockinger","year":"2014","journal-title":"Annu Rev Immunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/srep12689","article-title":"Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles","volume":"5","author":"Hubbard","year":"2015","journal-title":"Sci Rep"},{"key":"B38","doi-asserted-by":"publisher","first-page":"16024","DOI":"10.1038\/nmicrobiol.2016.24","article-title":"Developmental dynamics of the preterm infant gut microbiota and antibiotic resistome","volume":"1","author":"Gibson","year":"2016","journal-title":"Nat Microbiol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-312819","article-title":"Human milk oligosaccharide composition predicts risk of necrotising enterocolitis in preterm infants","volume":"67","author":"Autran","year":"2018","journal-title":"Gut"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-019-0740-x","article-title":"Indole-3-lactic acid, a metabolite of tryptophan, secreted by Bifidobacterium longum subspecies infantis is anti-inflammatory in the immature intestine","volume":"88","author":"Meng","year":"2020","journal-title":"Pediatr Res"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201200594","article-title":"Major phenylpropanoid-derived metabolites in the human gut can arise from microbial fermentation of protein","volume":"57","author":"Russell","year":"2013","journal-title":"Mol Nutr Food Res"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10410","article-title":"Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children","volume":"7","author":"Korpela","year":"2016","journal-title":"Nat Commun"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.0c05205","article-title":"Indole-3-propionic acid improved the intestinal barrier by enhancing epithelial barrier and mucus barrier","volume":"69","author":"Li","year":"2021","journal-title":"J Agric Food Chem"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-025-01396-6","article-title":"Microbial metabolite indole-3-propionic acid drives mitochondrial respiration in CD4(+)\u2009T cells to confer protection against intestinal inflammation","volume":"7","author":"Li","year":"2025","journal-title":"Nat Metab"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2025.05.051","article-title":"Prenatal supplementation with the gut-derived tryptophan metabolite indole-3-propionic acid alleviates colitis susceptibility in maternal immune-activated offspring mice","volume":"81","author":"He","year":"2026","journal-title":"J Adv Res"},{"key":"B46","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s12979-025-00552-6","article-title":"Activation of aryl hydrocarbon receptor signaling by indole-3-lactic acid from Bacillus velezensis DS2 reinforces gut mucosal immunity and attenuates inflammaging in aged mice","volume":"23","author":"Liu","year":"2025","journal-title":"Immun Ageing"},{"key":"B47","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/s41522-025-00898-1","article-title":"Microbiota-derived indole-3-acetic acid alleviates rumen epithelial barrier dysfunction during the peripartum period through AhR signaling","volume":"12","author":"Li","year":"2025","journal-title":"NPJ Biofilms Microbiomes"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3390\/ijms262311260","article-title":"The gut microbial metabolite indole-3-acetic acid reprograms systemic homeostasis and ameliorates IBD-associated cachexia independent of food intake","volume":"26","author":"Tomii","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.157659","article-title":"Radix Aucklandiae inhibits M1 macrophage polarization to alleviate ulcerative colitis by modulating gut microbial production of indole-3-aldehyde","volume":"150","author":"Tang","year":"2025","journal-title":"Phytomedicine"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae973","article-title":"Generic diagramming platform (GDP): a comprehensive database of high-quality biomedical graphics","volume":"53","author":"Jiang","year":"2025","journal-title":"Nucleic Acids Res"},{"key":"B51","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1186\/s13578-023-01046-y","article-title":"Modulating AHR function offers exciting therapeutic potential in gut immunity and inflammation","volume":"13","author":"Chen","year":"2023","journal-title":"Cell Biosci"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.18534","article-title":"Cell-permeable JNK-inhibitory peptide regulates intestinal barrier function and inflammation to ameliorate necrotizing enterocolitis","volume":"28","author":"Bu","year":"2024","journal-title":"J Cell Mol Med"},{"key":"B53","doi-asserted-by":"publisher","first-page":"42737","DOI":"10.1038\/s41598-025-26899-w","article-title":"IL-27Ra promotes the progression of neonatal necrotizing enterocolitis","volume":"15","author":"Yang","year":"2025","journal-title":"Sci Rep"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00256.2024","article-title":"Indole-3-propionic acid protects medium-diversity colitic mice via barrier enhancement preferentially over anti-inflammatory effects","volume":"328","author":"Nieves","year":"2025","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2025.1645561","article-title":"Gut microbial metabolite indole-3-propionic acid inhibits inflammation and restores blood-milk barrier in S. aureus- induced mastitis by targeting aryl hydrocarbon receptor","volume":"16","author":"Zhao","year":"2025","journal-title":"Front Microbiol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.molimm.2025.12.011","article-title":"Indole-3-propionic acid exerts radio-protective effects by modulating Wnt1\/STAT3 pathway to alleviate oxidative stress and neuroinflammation in microglia","volume":"189","author":"Si","year":"2025","journal-title":"Mol Immunol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202515794","article-title":"Lactobacillus salivarius-derived indole-3-acetic acid promotes AHR-PARP1 axis-mediated DNA repair to mitigate intestinal aging","volume":"13","author":"Cao","year":"2026","journal-title":"Adv Sci (Weinh)"},{"key":"B58","doi-asserted-by":"publisher","first-page":"193","DOI":"10.4049\/immunohorizons.2100018","article-title":"Indole-3-carbinol-dependent aryl hydrocarbon receptor signaling attenuates the inflammatory response in experimental necrotizing enterocolitis","volume":"5","author":"Nolan","year":"2021","journal-title":"Immunohorizons"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1668173","article-title":"The AhR\/IL-22 axis in chronic gut inflammation: unraveling mechanisms and therapeutic prospects","volume":"16","author":"Kang","year":"2025","journal-title":"Front Immunol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20192195","article-title":"The role of IL-22 in intestinal health and disease","volume":"217","author":"Keir","year":"2020","journal-title":"J Exp Med"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1710733","article-title":"Gut microbiota-derived metabolites modulate Treg\/Th17 balance: novel therapeutic targets in autoimmune diseases","volume":"16","author":"Li","year":"2025","journal-title":"Front Immunol"},{"key":"B62","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s41392-025-02500-8","article-title":"The aryl hydrocarbon receptor: structure, signaling, physiology and pathology","volume":"11","author":"Coumoul","year":"2026","journal-title":"Signal Transduct Target Ther"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2022.115371","article-title":"Functions of the aryl hydrocarbon receptor (AHR) beyond the canonical AHR\/ARNT signaling pathway","volume":"208","author":"Sondermann","year":"2023","journal-title":"Biochem Pharmacol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.gtc.2024.11.001","article-title":"Dysbiotic microbiota in necrotizing enterocolitis: insights into pathogenesis, treatment, and prevention","volume":"54","author":"Frazer","year":"2025","journal-title":"Gastroenterol Clin North Am"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13092288","article-title":"Necrotizing enterocolitis: a comprehensive review on Toll-like receptor 4-mediated pathophysiology, clinical, and therapeutic insights","volume":"13","author":"Ishiyama","year":"2025","journal-title":"Biomedicines"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-025-04495-y","article-title":"Gut microbiota in necrotizing enterocolitis: a bibliometric and visualization analysis","author":"Pei","year":"2025","journal-title":"Pediatr Res"},{"key":"B67","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1038\/s42003-025-09438-1","article-title":"L-cystine alleviates necrotizing enterocolitis by regulating ferroptosis and Th17 cell differentiation via the IL-6\/STAT3 pathway","volume":"9","author":"Zhu","year":"2025","journal-title":"Commun Biol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2025.1574792","article-title":"Quercetin ameliorates obesity and inflammation via microbial metabolite indole-3-propionic acid in high fat diet-induced obese mice","volume":"12","author":"Lu","year":"2025","journal-title":"Front Nutr"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1039\/d5fo03645c","article-title":"From microbiota to metabolomics: how Bifidobacterium infantis YLGB-1496 shields neonates from necrotizing enterocolitis","volume":"16","author":"Li","year":"2025","journal-title":"Food Funct"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1111\/all.16684","article-title":"Bifidobacterium breve M-16V alleviates cow's milk allergy in a mouse model via gut microbiota-derived indole-3-propionic acid-aryl hydrocarbon receptor signaling axis","author":"Shao","year":"2025","journal-title":"Allergy"},{"key":"B71","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1021\/acs.jafc.5c09843","article-title":"Lactiplantibacillus plantarum JY039 ameliorates necrotizing enterocolitis via intestinal stem cell regeneration","volume":"74","author":"Guo","year":"2026","journal-title":"J Agric Food Chem"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2024.2347722","article-title":"Microbiota-derived I3A protects the intestine against radiation injury by activating AhR\/IL-10\/Wnt signaling and enhancing the abundance of probiotics","volume":"16","author":"Xie","year":"2024","journal-title":"Gut Microbes"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26157080","article-title":"Gut microbial metabolites of tryptophan augment enteroendocrine cell differentiation in human colonic organoids: therapeutic potential for dysregulated GLP1 secretion in obesity","volume":"26","author":"Hart","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2025.12.046","article-title":"Cetobacterium somerae ZNN-1 promotes goblet cell differentiation through glutamine-mediated Notch signaling suppression","author":"Zhou","year":"2025","journal-title":"J Adv Res"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000046436","article-title":"Comparisons of fecal microbiota and cytokines in preterm infants preceding necrotizing enterocolitis and feeding intolerance: an observational study","volume":"104","author":"Jun","year":"2025","journal-title":"Med (Baltimore)"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202505154","article-title":"The gut resistome atlas in preterm infants enables prediction of necrotizing enterocolitis onset","volume":"12","author":"Zeng","year":"2025","journal-title":"Adv Sci (Weinh)"},{"key":"B77","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.jpeds.2021.12.070","article-title":"Bifidobacteriumlongum subsp. infantis EVC001 administration is associated with a significant reduction in the incidence of necrotizing enterocolitis in very low birth weight infants","volume":"244","author":"Tobias","year":"2022","journal-title":"J Pediatr"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-023-02716-w","article-title":"Bifidobacterium infantis as a probiotic in preterm infants: a systematic review and meta-analysis","volume":"94","author":"Batta","year":"2023","journal-title":"Pediatr Res"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms13092213","article-title":"Gut microbiota and neurodevelopment in preterm infants: mechanistic insights and prospects for clinical translation","volume":"13","author":"Dai","year":"2025","journal-title":"Microorganisms"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.116431","article-title":"Bacterial metabolite patterns of infants receiving multi-strain probiotics and risk of late-onset sepsis","volume":"44","author":"WasChina","year":"2025","journal-title":"Cell Rep"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2025.114961","article-title":"Increase in necrotizing enterocolitis with cessation of Bifidobacteriumlongum ssp. infantis administration in very low birthweight infants: a single center retrospective cohort study","volume":"291","author":"Selesner","year":"2025","journal-title":"J Pediatr"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.3390\/nu17081329","article-title":"Butyrate producers in very low birth weight infants with neither culture-proven sepsis nor necrotizing enterocolitis","volume":"17","author":"Thatrimontrichai","year":"2025","journal-title":"Nutrients"},{"key":"B83","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1186\/s12876-025-03788-0","article-title":"The effectiveness of treatment with probiotics in preventing necrotizing enterocolitis and related mortality: results from an umbrella meta-analysis on meta-analyses of randomized controlled trials","volume":"25","author":"Han","year":"2025","journal-title":"BMC Gastroenterol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.94762","article-title":"Effect of probiotic supplementation in preventing necrotizing enterocolitis sepsis and mortality among preterm and very low birth weight infants: a systematic review and meta-analysis","volume":"17","author":"Kalantar","year":"2025","journal-title":"Cureus"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmii.2020.03.029","article-title":"Lactobacillus rhamnosus sepsis associated with probiotic therapy in an extremely preterm infant: pathogenesis and a review for clinicians","volume":"54","author":"Chiang","year":"2021","journal-title":"J Microbiol Immunol Infect"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-025-04072-3","article-title":"Incidence of probiotic sepsis and morbidity risk in premature infants: a meta-analysis","author":"Feldman","year":"2025","journal-title":"Pediatr Res"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-021-00970-4","article-title":"Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut","volume":"6","author":"Laursen","year":"2021","journal-title":"Nat Microbiol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1128\/mmbr.00094-23","article-title":"Linking human milk oligosaccharide metabolism and early life gut microbiota: bifidobacteria and beyond","volume":"88","author":"Lordan","year":"2024","journal-title":"Microbiol Mol Biol Rev"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.103542","article-title":"Untangling human milk oligosaccharides and infant gut microbiome","volume":"25","author":"Masi","year":"2022","journal-title":"iScience"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-322771","article-title":"Human milk oligosaccharide DSLNT and gut microbiome in preterm infants predicts necrotising enterocolitis","volume":"70","author":"Masi","year":"2021","journal-title":"Gut"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.3390\/nu12020389","article-title":"Postbiotics for preventing and treating common infectious diseases in children: a systematic review","volume":"12","author":"Malag\u00f3n-Rojas","year":"2020","journal-title":"Nutrients"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2023.1120459","article-title":"Current and future methods of probiotic therapy for necrotizing enterocolitis","volume":"11","author":"Sajankila","year":"2023","journal-title":"Front Pediatr"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2309032120","article-title":"Bacterial indole-3-lactic acid affects epithelium-macrophage crosstalk to regulate intestinal homeostasis","volume":"120","author":"Yu","year":"2023","journal-title":"Proc Natl Acad Sci USA"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.3390\/nu17243907","article-title":"Gut microbiome composition and variance are modified by degree of growth failure in preterm infants: a prospective study","volume":"17","author":"Stumpf","year":"2025","journal-title":"Nutrients"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.3390\/metabo14110570","article-title":"Gut microbiota-derived metabolites and their role in the pathogenesis of necrotizing enterocolitis in preterm infants: a narrative review","volume":"14","author":"Provitera","year":"2024","journal-title":"Metabolites"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-043020-090050","article-title":"Diet-host-microbiota interactions shape aryl hydrocarbon receptor ligand production to modulate intestinal homeostasis","volume":"41","author":"Han","year":"2021","journal-title":"Annu Rev Nutr"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.3390\/toxics13110993","article-title":"Aryl hydrocarbon receptor-mediated disruption of intestinal epithelial barrier integrity by dioxin isomers","volume":"13","author":"Kakutani","year":"2025","journal-title":"Toxics"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.3390\/children12040498","article-title":"Advances in artificial intelligence and machine learning for precision medicine in necrotizing enterocolitis and neonatal sepsis: a state-of-the-art review","volume":"12","author":"Duci","year":"2025","journal-title":"Children (Basel)"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2026.1753617","article-title":"The interplay mechanisms between gut microbiota and ferroptosis in inflammatory bowel disease","volume":"17","author":"Shi","year":"2026","journal-title":"Front Immunol"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.5c14176","article-title":"Tween 80 exposure induces colitis by disrupting intestinal tryptophan metabolism","volume":"60","author":"Zhang","year":"2026","journal-title":"Environ Sci Technol"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2024.2422468","article-title":"Reverse engineering the gut-brain axis and microbiome-metabolomics for symbiotic\/pathogenic balance in neurodegenerative diseases","volume":"16","author":"Munir","year":"2024","journal-title":"Gut Microbes"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1782006\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T05:47:44Z","timestamp":1776059264000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1782006\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,13]]},"references-count":101,"alternative-id":["10.3389\/fimmu.2026.1782006"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1782006","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,13]]},"article-number":"1782006"}}