{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:19:09Z","timestamp":1787170749182,"version":"build-2736575974"},"reference-count":53,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,10,5]],"date-time":"2024-10-05T00:00:00Z","timestamp":1728086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chungnam National University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Regular exercise as part of one\u2019s lifestyle is well-recognized for its beneficial effect on several diseases such as cardiovascular disease and obesity; however, many questions remain unanswered regarding the effects of exercise on the gut environment. This study aimed to investigate the impact of long-term endurance exercise on modulating inflammation and endoplasmic reticulum (ER) stress. Fifteen-week-old male Sprague-Dawley (SD) rats were subjected to six months of endurance treadmill training, while age-matched controls remained sedentary. Results showed that IL-6 mRNA levels in colon tissues were significantly higher in the exercise group compared to the sedentary group. Exercise activated a significant ER stress-induced survival pathway by increasing BiP and phosphorylation of eIF2\u03b1 (p-eIF2\u03b1) expressions in the liver and colon, while decreasing CHOP in the liver. Gene expressions of MUC2, Occludin, and Claudin-2 were increased in the colon of the exercise group, indicating enhanced intestinal integrity. Furthermore, the data showed a positive correlation between microbiota \u03b1-diversity and BiP (r = 0.464~0.677, p &lt; 0.05). Populations of Desulfovibrio C21 c20 were significantly greater in the exercise group than the sedentary group. Additionally, predicted functions of the gut microbial community in terms of enzymes and pathways supported the enhancement of fatty-acid-related processes by exercise. These findings suggest that prolonged endurance exercise can affect the colon environment, which is likely related to changes in inflammation, ER stress, mucin layers and tight junctions, associated with modifications in the gut microbiome.<\/jats:p>","DOI":"10.3390\/ijms251910742","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T06:23:18Z","timestamp":1728282198000},"page":"10742","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Effect of Endurance Exercise Training on Gut Microbiota and ER Stress"],"prefix":"10.3390","volume":"25","author":[{"given":"Eun Ji","family":"Yoon","sequence":"first","affiliation":[{"name":"Research Center for Microbiome-Brain Disorders, Chungnam University, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9917-6652","authenticated-orcid":false,"given":"So Rok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6084-7700","authenticated-orcid":false,"given":"Beulah Favour","family":"Ortutu","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Oh","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Sport Science, Hannam University, Daejeon 34430, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8068-0672","authenticated-orcid":false,"given":"Varun","family":"Jaiswal","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Gachon University, Gyeonggi-do 13120, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sooyeon","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-In","family":"Yoon","sequence":"additional","affiliation":[{"name":"Research Center for Microbiome-Brain Disorders, Chungnam University, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Ki","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Sport Science, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Hwan","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Sport Science, Hannam University, Daejeon 34430, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8353-3619","authenticated-orcid":false,"given":"Hae-Jeung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Gachon University, Gyeonggi-do 13120, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9265-2409","authenticated-orcid":false,"given":"Jin Ah","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,5]]},"reference":[{"key":"ref_1","first-page":"e33475","article-title":"Role of Physical Activity on Mental Health and Well-Being: A Review","volume":"15","author":"Mahindru","year":"2023","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1136\/bjsports-2020-102955","article-title":"World Health Organization 2020 guidelines on physical activity and sedentary behaviour","volume":"54","author":"Bull","year":"2020","journal-title":"Br. J. Sports Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e1077","DOI":"10.1016\/S2214-109X(18)30357-7","article-title":"Worldwide trends in insufficient physical activity from 2001 to 2016: A pooled analysis of 358 population-based surveys with 1\u00b79 million participants","volume":"6","author":"Guthold","year":"2018","journal-title":"Lancet Glob. Health"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.2147\/DMSO.S257687","article-title":"Aerobic Exercise and Metabolic Syndrome: The Role of Sympathetic Activity and the Redox System","volume":"13","author":"Monda","year":"2020","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Myers, J., Kokkinos, P., and Nyelin, E. (2019). Physical Activity, Cardiorespiratory Fitness, and the Metabolic Syndrome. Nutrients, 11.","DOI":"10.3390\/nu11071652"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41569-020-0354-3","article-title":"The effects of endurance exercise on the heart: Panacea or poison?","volume":"17","author":"Sharma","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Thirupathi, A., Wang, M., Lin, J.K., Fekete, G., Istvan, B., Baker, J.S., and Gu, Y. (2021). Effect of Different Exercise Modalities on Oxidative Stress: A Systematic Review. Biomed. Res. Int., 2021.","DOI":"10.1155\/2021\/1947928"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1123\/ijspp.2022-0018","article-title":"Simple Approach to Defining Training Intensity in Endurance Runners","volume":"17","author":"Foster","year":"2022","journal-title":"Int. J. Sports Physiol. Perform."},{"key":"ref_9","first-page":"1082","article-title":"Physical Exercise Decreases Endoplasmic Reticulum Stress in Central and Peripheral Tissues of Rodents: A Systematic Review","volume":"13","author":"Badicu","year":"2023","journal-title":"Eur. J. Investig. Health Psychol. Educ."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s40279-016-0566-1","article-title":"The Antioxidant Effect of Exercise: A Systematic Review and Meta-Analysis","volume":"47","author":"Sales","year":"2017","journal-title":"Sports Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s12970-016-0155-6","article-title":"Exercise-induced stress behavior, gut-microbiota-brain axis and diet: A systematic review for athletes","volume":"13","author":"Clark","year":"2016","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Cerqueira, \u00c9., Marinho, D.A., Neiva, H.P., and Louren\u00e7o, O. (2019). Inflammatory Effects of High and Moderate Intensity Exercise\u2014A Systematic Review. Front. Physiol., 10.","DOI":"10.3389\/fphys.2019.01550"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Gubert, C., Kong, G., Renoir, T., and Hannan, A.J. (2020). Exercise, diet and stress as modulators of gut microbiota: Implications for neurodegenerative diseases. Neurobiol. Dis., 134.","DOI":"10.1016\/j.nbd.2019.104621"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Gallot, Y.S., and Bohnert, K.R. (2021). Confounding Roles of ER Stress and the Unfolded Protein Response in Skeletal Muscle Atrophy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052567"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/jcp.25852","article-title":"Emerging roles of ER stress and unfolded protein response pathways in skeletal muscle health and disease","volume":"233","author":"Bohnert","year":"2018","journal-title":"J. Cell Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.vph.2017.05.005","article-title":"Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases","volume":"100","author":"Incalza","year":"2018","journal-title":"Vascul Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"15327","DOI":"10.1074\/jbc.M114.633560","article-title":"The Endoplasmic Reticulum Stress Sensor IRE1 alpha in Intestinal Epithelial Cells Is Essential for Protecting against Colitis","volume":"290","author":"Zhang","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.jshs.2016.05.001","article-title":"Endurance exercise and gut microbiota: A review","volume":"6","author":"Mach","year":"2017","journal-title":"J. Sport. Health Sci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"(2019). The Integrative Human Microbiome Project. Nature, 569, 641\u2013648.","DOI":"10.1038\/s41586-019-1238-8"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Pearce, S.C., Al-Jawadi, A., Kishida, K., Yu, S., Hu, M., Fritzky, L.F., Edelblum, K.L., Gao, N., and Ferraris, R.P. (2018). Marked differences in tight junction composition and macromolecular permeability among different intestinal cell types. BMC Biol., 16.","DOI":"10.1186\/s12915-018-0481-z"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e442","DOI":"10.1111\/sms.12347","article-title":"Ultra-endurance exercise induces stress and inflammation and affects circulating hematopoietic progenitor cell function","volume":"25","author":"Stelzer","year":"2015","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"102353","DOI":"10.1016\/j.psj.2022.102353","article-title":"Dietary metabolizable energy and crude protein levels affect pectoral muscle composition and gut microbiota in native growing chickens","volume":"102","author":"Chang","year":"2023","journal-title":"Poult. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/s41587-020-0548-6","article-title":"PICRUSt2 for prediction of metagenome functions","volume":"38","author":"Douglas","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"D353","DOI":"10.1093\/nar\/gkw1092","article-title":"KEGG: New perspectives on genomes, pathways, diseases and drugs","volume":"45","author":"Kanehisa","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"D445","DOI":"10.1093\/nar\/gkz862","article-title":"The MetaCyc database of metabolic pathways and enzymes\u2014A 2019 update","volume":"48","author":"Caspi","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e16087","DOI":"10.14814\/phy2.16087","article-title":"Associations between various markers of intestinal barrier and immune function after a high-intensity exercise challenge","volume":"12","author":"Folkesson","year":"2024","journal-title":"Physiol. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.jshs.2019.05.002","article-title":"Exercise induces tissue hypoxia and HIF-1\u03b1 redistribution in the small intestine","volume":"9","author":"Wu","year":"2020","journal-title":"J. Sport. Health Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"289","DOI":"10.3390\/dietetics2030021","article-title":"Exercise-Induced Gastrointestinal Symptoms in Endurance Sports: A Review of Pathophysiology, Symptoms, and Nutritional Management","volume":"2","author":"Ribichini","year":"2023","journal-title":"Dietetics"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez-Urb\u00e1n, A.J., Drago-Serrano, M.E., Res\u00e9ndiz-Albor, A.A., Sierra-Ram\u00edrez, J.A., Guzm\u00e1n-Mej\u00eda, F., Oros-Pantoja, R., and God\u00ednez-Victoria, M. (2024). Moderate Aerobic Exercise Induces Homeostatic IgA Generation in Senile Mice. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202406.1077.v1"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1126\/science.aaa0079","article-title":"METABOLISM. S-Nitrosylation links obesity-associated inflammation to endoplasmic reticulum dysfunction","volume":"349","author":"Yang","year":"2015","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/s41392-023-01570-w","article-title":"Endoplasmic reticulum stress: Molecular mechanism and therapeutic targets","volume":"8","author":"Chen","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1089\/ars.2014.5851","article-title":"Endoplasmic reticulum stress and oxidative stress in cell fate decision and human disease","volume":"21","author":"Cao","year":"2014","journal-title":"Antioxid. Redox Signal"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"598","DOI":"10.3390\/gastroent14040042","article-title":"Autophagy and Apoptosis in Inflammatory Bowel Disease","volume":"14","author":"Kouroumalis","year":"2023","journal-title":"Gastroenterol. Insights"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7060","DOI":"10.1111\/febs.15731","article-title":"The role of goblet cells in viral pathogenesis","volume":"288","author":"Cortez","year":"2021","journal-title":"FEBS J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jnutbio.2018.07.010","article-title":"Gut microbes as future therapeutics in treating inflammatory and infectious diseases: Lessons from recent findings","volume":"61","author":"Mukherjee","year":"2018","journal-title":"J. Nutr. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1900\/RDS.2019.15.35","article-title":"Impact of Physical Exercise on Gut Microbiome, Inflammation, and the Pathobiology of Metabolic Disorders","volume":"15","author":"Sohail","year":"2019","journal-title":"Rev. Diabet. Stud."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8787","DOI":"10.3748\/wjg.v21.i29.8787","article-title":"Role of the normal gut microbiota","volume":"21","author":"Jandhyala","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.metabol.2017.01.007","article-title":"Gut microbiota interactions with the immunomodulatory role of vitamin D in normal individuals","volume":"69","author":"Luthold","year":"2017","journal-title":"Metabolism"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1084\/jem.20180448","article-title":"The gut microbiome: Relationships with disease and opportunities for therapy","volume":"216","author":"Durack","year":"2019","journal-title":"J. Exp. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1021\/acs.jafc.8b04859","article-title":"Novel histidine kinase gene HisK2301 from Rhodosporidium kratochvilovae contributes to cold adaption by promoting biosynthesis of polyunsaturated fatty acids and glycerol","volume":"67","author":"He","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s13568-018-0629-9","article-title":"The influence of in vitro pectin fermentation on the human fecal microbiome","volume":"8","author":"Bang","year":"2018","journal-title":"AMB Express"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Trommelen, J., Fuchs, C.J., Beelen, M., Lenaerts, K., Jeukendrup, A.E., Cermak, N.M., and van Loon, L.J. (2017). Fructose and Sucrose Intake Increase Exogenous Carbohydrate Oxidation during Exercise. Nutrients, 9.","DOI":"10.3390\/nu9020167"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.cmet.2021.12.016","article-title":"Atlas of exercise metabolism reveals time-dependent signatures of metabolic homeostasis","volume":"34","author":"Sato","year":"2022","journal-title":"Cell Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5311","DOI":"10.1007\/s00253-019-09786-z","article-title":"Structural modulation of gut microbiota reveals Coix seed contributes to weight loss in mice","volume":"103","author":"Liu","year":"2019","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s12986-019-0344-9","article-title":"Aerobic exercise decreases chemerin\/CMKLR1 in the serum and peripheral metabolic organs of obesity and diabetes rats by increasing PPAR\u03b3","volume":"16","author":"Lin","year":"2019","journal-title":"Nutr. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.jshs.2018.09.001","article-title":"Regular moderate aerobic exercise improves high-fat diet-induced nonalcoholic fatty liver disease via monoacylglycerol O-acyltransferase 1 pathway suppression","volume":"9","author":"Baek","year":"2020","journal-title":"J. Sport. Health Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"32","DOI":"10.12965\/jer.1835166.583","article-title":"Effects of regular-moderate exercise on high-fat diet-induced intramyocellular lipid accumulation in the soleus muscle of Sprague-Dawley rats","volume":"14","author":"Baek","year":"2018","journal-title":"J. Exerc. Rehabil."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Estaki, M., Jiang, L., Bokulich, N.A., McDonald, D., Gonzalez, A., Kosciolek, T., Martino, C., Zhu, Q., Birmingham, A., and Vazquez-Baeza, Y. (2020). QIIME 2 Enables Comprehensive End-to-End Analysis of Diverse Microbiome Data and Comparative Studies with Publicly Available Data. Curr. Protoc. Bioinform., 70.","DOI":"10.1002\/cpbi.100"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2","volume":"37","author":"Bolyen","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"146","DOI":"10.11620\/IJOB.2021.46.3.146","article-title":"Trimming conditions for DADA2 analysis in QIIME2 platform","volume":"46","author":"Yeuni","year":"2021","journal-title":"Int. J. Oral Biol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Bokulich, N.A., Kaehler, B.D., Rideout, J.R., Dillon, M., Bolyen, E., Knight, R., Huttley, G.A., and Gregory Caporaso, J. (2018). Optimizing taxonomic classification of marker-gene amplicon sequences with QIIME 2\u2019s q2-feature-classifier plugin. Microbiome, 6.","DOI":"10.1186\/s40168-018-0470-z"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4220","DOI":"10.1111\/1462-2920.15670","article-title":"Synergistic effects of exercise and catalase overexpression on gut microbiome","volume":"24","author":"Amos","year":"2022","journal-title":"Environ. Microbiol."},{"key":"ref_53","first-page":"1","article-title":"ALDEx2: ANOVA-Like Differential Expression tool for compositional data","volume":"20","author":"Gloor","year":"2015","journal-title":"ALDEX Man. Modul."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/19\/10742\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:11:17Z","timestamp":1760112677000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/19\/10742"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,5]]},"references-count":53,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["ijms251910742"],"URL":"https:\/\/doi.org\/10.3390\/ijms251910742","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,5]]}}}