{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:27:27Z","timestamp":1790792847882,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T00:00:00Z","timestamp":1711324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Korean government (MSIT)","doi-asserted-by":"publisher","award":["NRF-2023R1A2C1006547"],"award-info":[{"award-number":["NRF-2023R1A2C1006547"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korean government (MSIT)","doi-asserted-by":"publisher","award":["K2125701"],"award-info":[{"award-number":["K2125701"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002642","name":"Korea University","doi-asserted-by":"publisher","award":["NRF-2023R1A2C1006547"],"award-info":[{"award-number":["NRF-2023R1A2C1006547"]}],"id":[{"id":"10.13039\/501100002642","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002642","name":"Korea University","doi-asserted-by":"publisher","award":["K2125701"],"award-info":[{"award-number":["K2125701"]}],"id":[{"id":"10.13039\/501100002642","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The pathophysiology of functional bowel disorders is complex, involving disruptions in gut motility, visceral hypersensitivity, gut\u2013brain\u2013microbiota interactions, and psychosocial factors. Light pollution, as an environmental stressor, has been associated with disruptions in circadian rhythms and the aggravation of stress-related conditions. In this study, we investigated the effects of environmental stress, particularly continuous light exposure, on intestinal motility and inflammation using zebrafish larvae as a model system. We also evaluated the efficacy of probiotics, specifically Bifidobacterium longum (B. longum), at alleviating stress-induced constipation. Our results showed that continuous light exposure in zebrafish larvae increased the cortisol levels and reduced the intestinal motility, establishing a stress-induced-constipation model. We observed increased inflammatory markers and decreased intestinal neural activity in response to stress. Furthermore, the expressions of aquaporins and vasoactive intestinal peptide, crucial for regulating water transport and intestinal motility, were altered in the light-induced constipation model. Administration of probiotics, specifically B. longum, ameliorated the stress-induced constipation by reducing the cortisol levels, modulating the intestinal inflammation, and restoring the intestinal motility and neural activity. These findings highlight the potential of probiotics to modulate the gut\u2013brain axis and alleviate stress-induced constipation. Therefore, this study provides a valuable understanding of the complex interplay among environmental stressors, gut function, and potential therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms25073669","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T12:50:49Z","timestamp":1711371049000},"page":"3669","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Effect of Probiotics in Stress-Associated Constipation Model in Zebrafish (Danio rerio) Larvae"],"prefix":"10.3390","volume":"25","author":[{"given":"Ayoung","family":"Lee","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Korea University, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Korea University, Ansan 15355, Republic of Korea"},{"name":"Zebrafish Translational Medical Research Center, Korea University, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyoung","family":"Kang","sequence":"additional","affiliation":[{"name":"Zebrafish Translational Medical Research Center, Korea University, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong Hee","family":"Kang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Korea University, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Woo","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Korea University, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8371-9672","authenticated-orcid":false,"given":"Jung Wan","family":"Choe","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Korea University, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5632-7091","authenticated-orcid":false,"given":"Jong Jin","family":"Hyun","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Korea University, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Woo","family":"Jung","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Korea University, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Kul","family":"Jung","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Korea University, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1202-075X","authenticated-orcid":false,"given":"Ja Seol","family":"Koo","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Korea University, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung Joon","family":"Yim","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Korea University, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7425-1310","authenticated-orcid":false,"given":"Suhyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Zebrafish Translational Medical Research Center, Korea University, Ansan 15355, Republic of Korea"},{"name":"Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1053\/j.gastro.2016.02.031","article-title":"Bowel Disorders","volume":"150","author":"Mearin","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e14195","DOI":"10.1111\/nmo.14195","article-title":"Early adverse life events and post-traumatic stress disorder in patients with constipation and suspected disordered defecation","volume":"34","author":"Hendrix","year":"2021","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.bbi.2017.01.016","article-title":"Microbes and mental health: A review","volume":"66","author":"Rieder","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12144","DOI":"10.3748\/wjg.v20.i34.12144","article-title":"Irritable bowel syndrome: A clinical review","volume":"20","author":"Soares","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1210\/er.2013-1051","article-title":"The effects of light at night on circadian clocks and metabolism","volume":"35","author":"Fonken","year":"2014","journal-title":"Endocr. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41398-020-0694-0","article-title":"Circadian rhythm disruption and mental health","volume":"10","author":"Walker","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_7","first-page":"591","article-title":"Stress and the gut: Pathophysiology, clinical consequences, diagnostic approach and treatment options","volume":"62","author":"Konturek","year":"2011","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.dci.2016.02.020","article-title":"The zebrafish as a model to study intestinal inflammation","volume":"64","author":"Brugman","year":"2016","journal-title":"Dev. Comp. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.vascn.2013.03.006","article-title":"An evaluation of the non-invasive faecal pellet assessment method as an early drug discovery screen for gastrointestinal liability","volume":"68","author":"Marks","year":"2013","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.vascn.2004.02.008","article-title":"Gastrointestinal-tract models and techniques for use in safety pharmacology","volume":"49","author":"Harrison","year":"2004","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1111\/j.1365-2982.2008.01234.x","article-title":"Analysis of gastrointestinal physiology using a novel intestinal transit assay in zebrafish","volume":"21","author":"Field","year":"2009","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.brainres.2004.02.073","article-title":"The adult central nervous cholinergic system of a neurogenetic model animal, the zebrafish Danio rerio","volume":"1011","author":"Mueller","year":"2004","journal-title":"Brain Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"R711","DOI":"10.1152\/ajpregu.00671.2007","article-title":"Development of the corticosteroid stress axis and receptor expression in zebrafish","volume":"294","author":"Alsop","year":"2008","journal-title":"Am. J. Physiol. Integr. Comp. Physiol."},{"key":"ref_14","unstructured":"Cachat, J.M., Canavello, P.R., Elegante, M.F., Bartels, B.K., Elkhayat, S.I., Hart, P.C., Tien, A.K., Tien, D.H., Beeson, E., and Mohnot, S. (2011). Zebrafish Models in Neurobehavioral Research, Humana."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1080\/19768354.2021.1991472","article-title":"Prokinetic effects of diatrizoate meglumine (Gastrografin\u00ae) in a zebrafish for opioid-induced constipation model","volume":"25","author":"Kim","year":"2021","journal-title":"Anim. Cells Syst."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"72","DOI":"10.4291\/wjgp.v2.i5.72","article-title":"Cytokine-induced alterations of gastrointestinal motility in gastrointestinal disorders","volume":"2","author":"Akiho","year":"2011","journal-title":"World J. Gastrointest. Pathophysiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1111\/j.1572-0241.2000.02184.x","article-title":"Psychological disorders in patients with evacuation dis-orders and constipation in a tertiary practice","volume":"95","author":"Nehra","year":"2000","journal-title":"Am. J. Gastroenterol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1002\/ar.22403","article-title":"The Effects of Rearing Light Level and Duration Differences on the Optic Nerve, Brain, and Associated Structures in Developing Zebrafish Larvae: A Light and Transmission Electron Microscope Study","volume":"295","author":"Chapman","year":"2012","journal-title":"Anat. Rec."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1292\/jvms.22-0073","article-title":"Stress decreases contraction of the colon, and the effects of stress are different among the regions of the colon","volume":"84","author":"Ono","year":"2022","journal-title":"J. Vet. Med. Sci."},{"key":"ref_20","first-page":"218","article-title":"Chronic stress-induced alterations in mouse colonic 5-HT and defecation responses are strain dependent","volume":"15","author":"Clarke","year":"2011","journal-title":"Stress"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1016\/j.jcmgh.2021.08.021","article-title":"The Role of Intestinal Macrophages in Gastrointestinal Homeostasis: Heterogeneity and Implications in Disease","volume":"12","author":"Yip","year":"2021","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1172\/JCI200519229","article-title":"Human intestinal macrophages display profound in-flammatory anergy despite avid phagocytic and bacteriocidal activity","volume":"115","author":"Smythies","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1053\/j.gastro.2023.03.214","article-title":"American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation","volume":"164","author":"Chang","year":"2023","journal-title":"Gastroenterology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e13762","DOI":"10.1111\/nmo.13762","article-title":"European society of neurogastroenterology and motility guidelines on functional constipation in adults","volume":"32","author":"Serra","year":"2019","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1111\/j.1365-2036.2006.03238.x","article-title":"Chronic constipation: A survey of the patient perspective","volume":"25","author":"Johanson","year":"2007","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1016\/j.clnu.2022.10.015","article-title":"Probiotics and synbiotics in chronic constipation in adults: A systematic review and meta-analysis of randomized controlled trials","volume":"41","author":"Helander","year":"2022","journal-title":"Clin. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Shang, X., E, F.-F., Guo, K.-L., Li, Y.-F., Zhao, H.-L., Wang, Y., Chen, N., Nian, T., Yang, C.-Q., and Yang, K.-H. (2022). Effectiveness and Safety of Probiotics for Patients with Constipation-Predominant Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of 10 Randomized Controlled Trials. Nutrients, 14.","DOI":"10.3390\/nu14122482"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Chen, M., Liu, C., Dai, M., Wang, Q., Li, C., and Hung, W. (2022). Bifidobacterium lactis BL-99 modulates intestinal inflammation and functions in zebrafish models. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0262942"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1089\/zeb.2020.1877","article-title":"Probiotics Modulate Intestinal Motility and Inflammation in Zebrafish Models","volume":"17","author":"Wang","year":"2020","journal-title":"Zebrafish"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nrn3346","article-title":"Mind-altering microorganisms: The impact of the gut microbiota on brain and behaviour","volume":"13","author":"Cryan","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Reis, D.J., Ilardi, S.S., and Punt, S.E.W. (2018). The anxiolytic effect of probiotics: A systematic review and meta-analysis of the clinical and preclinical literature. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0199041"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"16b","DOI":"10.1155\/2011\/169319","article-title":"The pathophysiology of chronic constipation","volume":"25","author":"Andrews","year":"2011","journal-title":"Can. J. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1097\/MIB.0000000000000667","article-title":"Enteric Glial Cells: A New Frontier in Neurogastroen-terology and Clinical Target for Inflammatory Bowel Diseases","volume":"22","author":"Turco","year":"2016","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1038\/16040","article-title":"Nociceptive-specific activation of ERK in spinal neurons contributes to pain hypersensitivity","volume":"2","author":"Ji","year":"1999","journal-title":"Nat. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2174\/1876386300902010011","article-title":"c-Fos and pERK, which is a better marker for neuronal activation and central sensitization after noxious stimulation and tissue injury?","volume":"2","author":"Gao","year":"2009","journal-title":"Open Pain J."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhu, C., Chen, Z., and Jiang, Z. (2016). Expression, Distribution and Role of Aquaporin Water Channels in Human and Animal Stomach and Intestines. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17091399"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Ikarashi, N., Kon, R., and Sugiyama, K. (2016). Aquaporins in the Colon as a New Therapeutic Target in Diarrhea and Constipation. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17071172"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5003","DOI":"10.3168\/jds.2019-17836","article-title":"Lactobacillus rhamnosus FLRH93 protects against intestinal damage in mice induced by 5-fluorouracil","volume":"103","author":"Hu","year":"2020","journal-title":"J. Dairy Sci."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zhou, X., Mao, B., Tang, X., Zhang, Q., Zhao, J., Zhang, H., and Cui, S. (2023). Exploring the Dose\u2013Effect Relationship of Bifidobacterium longum in Relieving Loperamide Hydrochloride-Induced Constipation in Rats through Colon-Released Capsules. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076585"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e49","DOI":"10.1182\/blood-2010-10-314120","article-title":"mpeg1 promoter transgenes direct macrophage-lineage expression in zebrafish","volume":"117","author":"Ellett","year":"2011","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.devcel.2009.11.015","article-title":"Differential Regulation of Protrusion and Polarity by PI(3)K during Neutrophil Motility in Live Zebrafish","volume":"18","author":"Yoo","year":"2010","journal-title":"Dev. Cell"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ehsannia, S., Ahari, H., Kakoolaki, S., Anvar, S.A., and Yousefi, S. (2022). Effects of probiotics on Zebrafish model infected with Aeromonas hydrophila: Spatial distribution, antimicrobial, and histopathological investigation. BMC Microbiol., 22.","DOI":"10.1186\/s12866-022-02491-4"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"739591","DOI":"10.3389\/fimmu.2021.739591","article-title":"Activation of the TCA Cycle to Provide Immune Protection in Zebrafish Immunized by High Magnesium-Prepared Vibrio alginolyticus Vaccine","volume":"12","author":"Yang","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1080\/21505594.2020.1750123","article-title":"Malate enhances survival of zebrafish against Vibrio alginolyticus infection in the same manner as taurine","volume":"11","author":"Yang","year":"2020","journal-title":"Virulence"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ahi, E.P., Brunel, M., Tsakoumis, E., Chen, J., and Schmitz, M. (2022). Appetite regulating genes in zebrafish gut; a gene expression study. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0255201"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4277","DOI":"10.1002\/cne.22481","article-title":"Astroglial structures in the zebrafish brain","volume":"518","author":"Grupp","year":"2010","journal-title":"J. Comp. Neurol."},{"key":"ref_47","first-page":"58497","article-title":"High-throughput Measurement of Gut Transit Time Using Larval Zebrafish","volume":"23","author":"Cassar","year":"2018","journal-title":"J. Vis. Exp."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/7\/3669\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:18:30Z","timestamp":1760105910000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/7\/3669"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,25]]},"references-count":47,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["ijms25073669"],"URL":"https:\/\/doi.org\/10.3390\/ijms25073669","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,25]]}}}