{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:03:46Z","timestamp":1789625026904,"version":"build-2803163510"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Prolonged preoperative fasting is associated with intestinal dysbiosis, impaired mucosal homeostasis, and delayed postoperative recovery. Combined nutritional supplementation with glutamine, dietary fiber, and oligosaccharides has the potential to protect intestinal function during nutritional stress. In this study, we investigated the effects of this nutritional combination in a rat model of prolonged fasting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male Sprague-Dawley rats received oral supplementation with a combination of glutamine, dietary fiber, and oligosaccharides (GFO) or a 15% glucose solution twice daily for 9 days and were subjected to fasting from days 6 to 9. Jejunal morphology, short-chain fatty acid (SCFA) concentrations, intestinal gene expression, and gut microbiota composition were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fasting significantly reduced body weight, jejunal villous height, cecal weight, and the concentrations of acetate, n-butyrate, and n-valerate. Fasting was also associated with exploratory changes in gut microbiota composition and increased the expression of several Toll-like receptor (TLR), barrier, and autophagy-related genes in the jejunum. Supplementation with glutamine, dietary fiber, and oligosaccharides significantly attenuated the fasting-induced reduction in cecal weight and suppressed the upregulation of TLR5, TLR6, TLR8, CLDN1, CLDN3, OCLN, ZO-1, MUC3, ATG5, ATG12, Beclin1, p62, and LC3. Microbiota analysis showed that the relative abundance of sequences tentatively assigned to\n                      <jats:italic>Lactobacillus reuteri<\/jats:italic>\n                      in the supplemented group was comparable to that in the control group, whereas sequences tentatively assigned to\n                      <jats:italic>Bifidobacterium animalis<\/jats:italic>\n                      were detected predominantly in the supplemented group. The relative abundances of\n                      <jats:italic>Desulfovibrio, Bilophila<\/jats:italic>\n                      , and\n                      <jats:italic>Mucispirillum schaedleri<\/jats:italic>\n                      in the supplemented group appeared closer to those observed in the control group than to those in the fasting group. Furthermore, supplementation significantly increased propionate levels compared with the control group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Combined supplementation with glutamine, dietary fiber, and oligosaccharides attenuated several fasting-associated intestinal stress responses and was accompanied by exploratory changes in gut microbiota composition and SCFA profiles. These intestinal effects were accompanied by exploratory changes in gut microbiota composition and SCFA profiles, together with attenuation of fasting-associated changes in intestinal stress-related markers, suggesting that this nutritional strategy may help maintain intestinal homeostasis during prolonged fasting and may have potential applications in perioperative nutritional support.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1933552","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:32:29Z","timestamp":1789623149000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Combined glutamine, dietary fiber, and oligosaccharide supplementation attenuates fasting-associated intestinal dysbiosis and stress responses in rats"],"prefix":"10.3389","volume":"13","author":[{"given":"Yuta","family":"Murai","sequence":"first","affiliation":[{"name":"Shizuoka Medical Research Center for Disaster, Juntendo University","place":["Shizuoka, Japan"]},{"name":"Department of Surgery, Juntendo University Shizuoka Hospital","place":["Shizuoka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Iwasawa","sequence":"additional","affiliation":[{"name":"Shizuoka Medical Research Center for Disaster, Juntendo University","place":["Shizuoka, Japan"]},{"name":"Institute of Life Innovation Studies, Toyo University","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Takeda","sequence":"additional","affiliation":[{"name":"Shizuoka Medical Research Center for Disaster, Juntendo University","place":["Shizuoka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaho","family":"Ohki","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Graduate School of Health and Sports Sciences, Toyo University","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Kato","sequence":"additional","affiliation":[{"name":"Institute of Life Innovation Studies, Toyo University","place":["Tokyo, Japan"]},{"name":"Department of Nutritional Sciences, Graduate School of Health and Sports Sciences, Toyo University","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoaki","family":"Ito","sequence":"additional","affiliation":[{"name":"Shizuoka Medical Research Center for Disaster, Juntendo University","place":["Shizuoka, Japan"]},{"name":"Department of Surgery, Juntendo University Shizuoka Hospital","place":["Shizuoka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/j.clnu.2017.02.013","article-title":"ESPEN guideline: clinical nutrition in surgery","volume":"36","author":"Weimann","year":"2017","journal-title":"Clin Nutr."},{"key":"B2","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1001\/jamasurg.2016.4952","article-title":"Enhanced recovery after surgery: a review","volume":"152","author":"Ljungqvist","year":"2017","journal-title":"JAMA Surg."},{"key":"B3","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1001\/archsurg.137.2.174","article-title":"Nutritional approach in malnourished surgical patients: a prospective randomized study","volume":"137","author":"Braga","year":"2002","journal-title":"Arch Surg."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1097\/ALN.0000000000000795","article-title":"Promoting perioperative metabolic and nutritional care","volume":"123","author":"Gillis","year":"2015","journal-title":"Anesthesiology."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1016\/j.cell.2019.07.047","article-title":"Fasting-refeeding impacts immune cell dynamics and mucosal immune responses","volume":"178","author":"Nagai","year":"2019","journal-title":"Cell"},{"key":"B6","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1016\/j.clnu.2009.05.013","article-title":"Decreased food intake is a risk factor for mortality in hospitalised patients: the nutritionday survey 2006","volume":"28","author":"Hiesmayr","year":"2009","journal-title":"Clin Nutr."},{"key":"B7","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1177\/0884533609358997","article-title":"Understanding the role of nutrition and wound healing","volume":"25","author":"Stechmiller","year":"2010","journal-title":"Nutr Clin Pract."},{"key":"B8","doi-asserted-by":"publisher","first-page":"294","DOI":"10.3109\/08941939.2012.762073","article-title":"Peritonitis from perforated peptic ulcer and immune response","volume":"26","author":"Schietroma","year":"2013","journal-title":"J Invest Surg."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1016\/j.cmet.2014.11.008","article-title":"Diet and feeding pattern affect the diurnal dynamics of the gut microbiome","volume":"20","author":"Zarrinpar","year":"2014","journal-title":"Cell Metab."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1016\/j.cell.2016.11.003","article-title":"Microbiota diurnal rhythmicity programs host transcriptome oscillations","volume":"167","author":"Thaiss","year":"2016","journal-title":"Cell"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2403","DOI":"10.1152\/jappl.2001.90.6.2403","article-title":"Glutamine induces heat shock protein and protects against endotoxin shock in the rat","volume":"90","author":"Wischmeyer","year":"2001","journal-title":"J Appl Physiol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2022","DOI":"10.1097\/00003246-200209000-00011","article-title":"Glutamine supplementation in serious illness: a systematic review of the evidence","volume":"30","author":"Novak","year":"2002","journal-title":"Crit Care Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.3390\/nu5041417","article-title":"Fiber and prebiotics: mechanisms and health benefits","volume":"5","author":"Slavin","year":"2013","journal-title":"Nutrients."},{"key":"B14","doi-asserted-by":"publisher","first-page":"185","DOI":"10.3389\/fmicb.2016.00185","article-title":"Intestinal short chain fatty acids and their link with diet and human health","volume":"7","author":"Rios-Covian","year":"2016","journal-title":"Front Microbiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1007\/s10620-008-0478-5","article-title":"Glutamine decreases the duration of postoperative ileus after abdominal surgery: an experimental study of conscious dogs","volume":"54","author":"Ohno","year":"2009","journal-title":"Dig Dis Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s10388-018-0630-z","article-title":"Perioperative enteral supplementation with glutamine, fiber, and oligosaccharide reduces early postoperative surgical stress following esophagectomy for esophageal cancer","volume":"16","author":"Abe","year":"2019","journal-title":"Esophagus."},{"key":"B17","doi-asserted-by":"publisher","first-page":"101370","DOI":"10.1016\/j.ctcp.2021.101370","article-title":"The Effect of pro\/synbiotics on postoperative infections in colorectal cancer patients: a systematic review and meta-analysis","volume":"43","author":"Zeng","year":"2021","journal-title":"Complement Ther Clin Pract."},{"key":"B18","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.nut.2018.06.004","article-title":"Impact of the preoperative use of synbiotics in colorectal cancer patients: a prospective, randomized, double-blind, placebo-controlled study","volume":"58","author":"Polakowski","year":"2019","journal-title":"Nutrition."},{"key":"B19","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/nri3608","article-title":"Intestinal epithelial cells: regulators of barrier function and immune homeostasis","volume":"14","author":"Peterson","year":"2014","journal-title":"Nat Rev Immunol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/nri2653","article-title":"Intestinal mucosal barrier function in health and disease","volume":"9","author":"Turner","year":"2009","journal-title":"Nat Rev Immunol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.3390\/ijms18051051","article-title":"The roles of glutamine in the intestine and its implication in intestinal diseases","volume":"18","author":"Kim","year":"2017","journal-title":"Int J Mol Sci"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2143","DOI":"10.1007\/s00726-014-1773-4","article-title":"Glutamine and intestinal barrier function","volume":"47","author":"Wang","year":"2015","journal-title":"Amino Acids."},{"key":"B23","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1146\/annurev.nutr.23.011702.073036","article-title":"Trophic and cytoprotective nutrition for intestinal adaptation, mucosal repair, and barrier function","volume":"23","author":"Ziegler","year":"2003","journal-title":"Annu Rev Nutr."},{"key":"B24","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1017\/S0007114516004037","article-title":"Can probiotics modulate human disease by impacting intestinal barrier function?","volume":"117","author":"Bron","year":"2017","journal-title":"Br J Nutr."},{"key":"B25","doi-asserted-by":"publisher","first-page":"S49","DOI":"10.1093\/advances\/nmy063","article-title":"Mechanisms of action of probiotics","volume":"10","author":"Plaza-Diaz","year":"2019","journal-title":"Adv Nutr"},{"key":"B26","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/nrmicro2297","article-title":"Host interactions of probiotic bacterial surface molecules: comparison with commensals and pathogens","volume":"8","author":"Lebeer","year":"2010","journal-title":"Nat Rev Microbiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"757","DOI":"10.3389\/fmicb.2018.00757","article-title":"Role of Lactobacillus reuteri in human health and diseases","volume":"9","author":"Mu","year":"2018","journal-title":"Front Microbiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/nature12331","article-title":"Treg induction by a rationally selected mixture of clostridia strains from the human microbiota","volume":"500","author":"Atarashi","year":"2013","journal-title":"Nature."},{"key":"B29","doi-asserted-by":"publisher","first-page":"925","DOI":"10.3389\/fmicb.2016.00925","article-title":"Bifidobacteria and their role as members of the human gut microbiota","volume":"7","author":"O'Callaghan","year":"2016","journal-title":"Front Microbiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/nature09646","article-title":"Bifidobacteria can protect from enteropathogenic infection through production of acetate","volume":"469","author":"Fukuda","year":"2011","journal-title":"Nature."},{"key":"B31","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1111\/j.1574-6941.2002.tb00942.x","article-title":"Sulfate-reducing bacteria in human feces and their association with inflammatory bowel diseases","volume":"40","author":"Loubinoux","year":"2002","journal-title":"FEMS Microbiol Ecol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1097\/MCO.0000000000000526","article-title":"Cysteine-derived hydrogen sulfide and gut health: a matter of endogenous or bacterial origin","volume":"22","author":"Blachier","year":"2019","journal-title":"Curr Opin Clin Nutr Metab Care."},{"key":"B33","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1038\/nature11225","article-title":"Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-\/- mice","volume":"487","author":"Devkota","year":"2012","journal-title":"Nature."},{"key":"B34","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.chom.2019.03.004","article-title":"Mucispirillum schaedleri antagonizes Salmonella virulence to protect mice against colitis","volume":"25","author":"Herp","year":"2019","journal-title":"Cell Host Microbe"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1016\/j.cell.2016.05.041","article-title":"From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites","volume":"165","author":"Koh","year":"2016","journal-title":"Cell."},{"key":"B36","doi-asserted-by":"publisher","first-page":"277","DOI":"10.3389\/fimmu.2019.01486","article-title":"Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases","volume":"10","author":"Parada Venegas","year":"2019","journal-title":"Front Immunol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.3945\/jn.109.104638","article-title":"Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers","volume":"139","author":"Peng","year":"2009","journal-title":"J Nutr."},{"key":"B38","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1038\/nature12721","article-title":"Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells","volume":"504","author":"Furusawa","year":"2013","journal-title":"Nature."},{"key":"B39","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/nature12726","article-title":"Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation","volume":"504","author":"Arpaia","year":"2013","journal-title":"Nature."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1136\/gutjnl-2012-303611","article-title":"Butyricicoccus Pullicaecorum in inflammatory bowel disease","volume":"62","author":"Eeckhaut","year":"2013","journal-title":"Gut."},{"key":"B41","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1111\/j.1753-4887.2011.00388.x","article-title":"Propionate as a health-promoting microbial metabolite in the human gut","volume":"69","author":"Hosseini","year":"2011","journal-title":"Nutr Rev."},{"key":"B42","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/B978-0-12-800100-4.00003-9","article-title":"The role of short-chain fatty acids in health and disease","volume":"121","author":"Tan","year":"2014","journal-title":"Adv Immunol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1136\/gut.2006.094375","article-title":"Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease","volume":"56","author":"Zeissig","year":"2007","journal-title":"Gut."},{"key":"B44","doi-asserted-by":"publisher","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":"B45","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/nri1391","article-title":"Toll-like receptor signalling","volume":"4","author":"Akira","year":"2004","journal-title":"Nat Rev Immunol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/nri2707","article-title":"Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function","volume":"10","author":"Abreu","year":"2010","journal-title":"Nat Rev Immunol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1002\/ibd.21282","article-title":"Toll-like receptors in inflammatory bowel diseases: a decade later","volume":"16","author":"Cario","year":"2010","journal-title":"Inflamm Bowel Dis."},{"key":"B48","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/j.cell.2011.10.026","article-title":"Autophagy: renovation of cells and tissues","volume":"147","author":"Mizushima","year":"2011","journal-title":"Cell."},{"key":"B49","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.cell.2007.12.018","article-title":"Autophagy in the pathogenesis of disease","volume":"132","author":"Levine","year":"2008","journal-title":"Cell."},{"key":"B50","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1080\/15548627.2017.1402992","article-title":"Autophagy balances inflammation in innate immunity","volume":"14","author":"Deretic","year":"2018","journal-title":"Autophagy."},{"key":"B51","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/nri.2016.100","article-title":"Crosstalk between autophagy and inflammatory signalling pathways: balancing defence and homeostasis","volume":"16","author":"Cadwell","year":"2016","journal-title":"Nat Rev Immunol."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1933552\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:32:31Z","timestamp":1789623151000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1933552\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":51,"alternative-id":["10.3389\/fnut.2026.1933552"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2026.1933552","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]},"article-number":"1933552"}}