{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T06:21:41Z","timestamp":1784614901875,"version":"3.55.0"},"reference-count":30,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T00:00:00Z","timestamp":1623888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Gastrointestinal surgery imparts dramatic and lasting imbalances, or dysbiosis, to the composition of finely tuned microbial ecosystems. The aim of the present study was to use a mouse ileocecal resection (ICR) model to determine if tributyrin (TBT) supplementation could prevent the onset of microbial dysbiosis or alternatively enhance the recovery of the gut microbiota and reduce gastrointestinal inflammation. Methods: Male wild-type (129 s1\/SvlmJ) mice aged 8\u201315 weeks were separated into single cages and randomized 1:1:1:1 to each of the four experimental groups: control (CTR), preoperative TBT supplementation (PRE), postoperative TBT supplementation (POS), and combined pre- and postoperative supplementation (TOT). ICR was performed one week from baseline assessment with mice assessed at 1, 2, 3, and 4 weeks postoperatively. Primary outcomes included evaluating changes to gut microbial communities occurring from ICR to 4 weeks. Results: A total of 34 mice that underwent ICR (CTR n = 9; PRE n = 10; POS n = 9; TOT n = 6) and reached the primary endpoint were included in the analysis. Postoperative TBT supplementation was associated with an increased recolonization and abundance of anaerobic taxa including Bacteroides thetaiotomicorn, Bacteroides caecimuris, Parabacteroides distasonis, and Clostridia. The microbial recolonization of PRE mice was characterized by a bloom of aerotolerant organisms including Staphylococcus, Lactobacillus, Enteroccaceae, and Peptostreptococcacea. PRE mice had a trend towards decreased ileal inflammation as evidenced by decreased levels of IL-1\u03b2 (p = 0.09), IL-6 (p = 0.03), and TNF-\u03b1 (p &lt; 0.05) compared with mice receiving TBT postoperatively. In contrast, POS mice had trends towards reduced colonic inflammation demonstrated by decreased levels of IL-6 (p = 0.07) and TNF-\u03b1 (p = 0.07). These changes occurred in the absence of changes to fecal short-chain fatty acid concentrations or histologic injury scoring. Conclusions: Taken together, the results of our work demonstrate that the timing of tributyrin supplementation differentially modulates gastrointestinal inflammation and gut microbial recolonization following murine ICR.<\/jats:p>","DOI":"10.3390\/nu13062069","type":"journal-article","created":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T11:20:26Z","timestamp":1623928826000},"page":"2069","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Timing of Tributyrin Supplementation Differentially Modulates Gastrointestinal Inflammation and Gut Microbial Recolonization Following Murine Ileocecal Resection"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7855-6242","authenticated-orcid":false,"given":"Valentin","family":"Mocanu","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heekuk","family":"Park","sequence":"additional","affiliation":[{"name":"Columbia University Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8659-0934","authenticated-orcid":false,"given":"Jerry","family":"Dang","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Hotte","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6836-8619","authenticated-orcid":false,"given":"Aducio","family":"Thiesen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Laffin","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haili","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Birch","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8636-0714","authenticated-orcid":false,"given":"Karen","family":"Madsen","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.14748\/bmr.v27.2108","article-title":"Gut Microbiota and Health: A Review with Focus on Metabolic and Immunological Disorders and Microbial Remediation","volume":"27","author":"Pradhan","year":"2017","journal-title":"Biomed. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.freeradbiomed.2013.11.008","article-title":"Role of the enteric microbiota in intestinal homeostasis and inflammation","volume":"68","author":"Koboziev","year":"2014","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.gtc.2016.09.011","article-title":"The Gut Microbiota in Inflammatory Bowel Disease","volume":"46","author":"Sheehan","year":"2017","journal-title":"Gastroenterol. Clin. N. Am."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.3748\/wjg.v20.i5.1192","article-title":"Role of the gut microbiota in inflammatory bowel disease pathogenesis: What have we learnt in the past 10 years?","volume":"20","author":"Hold","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s11515-018-1490-6","article-title":"The journey of gut microbiome\u2014An introduction and its influence on metabolic disorders","volume":"13","author":"Chattopadhyay","year":"2018","journal-title":"Front. Biol."},{"key":"ref_6","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_7","doi-asserted-by":"crossref","unstructured":"Matija\u0161i\u0107, M., Me\u0161trovi\u0107, T., Peri\u0107, M., and Paljetak, H. (2016). \u010cip\u010di\u0107; Panek, M.; Bender, D.V.; Kele\u010di\u0107, D.L.; Krznari\u0107, \u017deljko; Verbanac, D. Modulating Composition and Metabolic Activity of the Gut Microbiota in IBD Patients. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17040578"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1556\/650.2015.30296","article-title":"Physiological patterns of intestinal microbiota. The role of dysbacteriosis in obesity, insulin resistance, diabetes and metabolic syndrome. A belbakteriota elettani Jell es a dysbacteriosis szerepe az elhizasban, inzulinrezisztenciaban, diabetesben es Metab szindromaban","volume":"157","author":"Halmos","year":"2016","journal-title":"Orvosi Hetil."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.1007\/s11605-020-04680-w","article-title":"The Biology of Anastomotic Healing\u2014the Unknown Overwhelms the Known","volume":"24","author":"Lam","year":"2020","journal-title":"J. Gastrointest. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1093\/ibd\/izx033","article-title":"Prebiotic Supplementation Following Ileocecal Resection in a Murine Model is Associated with a Loss of Microbial Diversity and Increased Inflammation","volume":"24","author":"Laffin","year":"2017","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Perry, T., Laffin, M., Fedorak, R.N., Thiesen, A., Dicken, B., and Madsen, K.L. (2017). Ileocolic resection is associated with increased susceptibility to injury in a murine model of colitis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0184660"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e131","DOI":"10.1002\/bjs.10760","article-title":"Gut microbiome influences on anastomotic leak and recurrence rates following colorectal cancer surgery","volume":"105","author":"Gaines","year":"2018","journal-title":"BJS"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5017","DOI":"10.3748\/wjg.v25.i34.5017","article-title":"Reducing anastomotic leak in colorectal surgery: The old dogmas and the new challenges","volume":"25","author":"Meyer","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/nrgastro.2016.139","article-title":"The gut microbiota and gastrointestinal surgery","volume":"14","author":"Guyton","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1177\/0148607112452306","article-title":"A Meta-Analysis of Probiotic and Synbiotic Use in Elective Surgery","volume":"37","author":"Kinross","year":"2012","journal-title":"J. Parenter. Enter. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1038\/s41591-019-0464-9","article-title":"Community ecology as a framework for human microbiome research","volume":"25","author":"Gilbert","year":"2019","journal-title":"Nat. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"100984","DOI":"10.1016\/j.psj.2021.01.007","article-title":"The effects of tributyrin supplementation on weight gain and intestinal gene expression in broiler chickens during Eimeria maxima-induced coccidiosis","volume":"100","author":"Hansen","year":"2021","journal-title":"Poult. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/9671919","article-title":"Tributyrin Supplementation Protects Immune Responses and Vasculature and Reduces Oxidative Stress in the Proximal Colon of Mice Exposed to Chronic-Binge Ethanol Feeding","volume":"2018","author":"Glueck","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.chom.2015.03.005","article-title":"Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function","volume":"17","author":"Kelly","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1097\/01.shk.0000140664.80530.bd","article-title":"Butyrate suppresses hypoxia-inducible factor-1 activity in intestinal epithelial cells under hypoxic conditions","volume":"22","author":"Miki","year":"2004","journal-title":"Shock"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1111\/acer.12428","article-title":"Tributyrin Supplementation Protects Mice from Acute Ethanol-Induced Gut Injury","volume":"38","author":"Cresci","year":"2014","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1053\/j.gastro.2008.03.009","article-title":"Hypoxia-Inducible Factor Augments Experimental Colitis Through an MIF\u2013Dependent Inflammatory Signaling Cascade","volume":"134","author":"Shah","year":"2008","journal-title":"Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sotira, S., Dell\u2019Anno, M., Caprarulo, V., Hejna, M., Pirrone, F., Callegari, M.L., Tucci, T.V., and Rossi, L. (2020). Effects of Tributyrin Supplementation on Growth Performance, Insulin, Blood Metabolites and Gut Microbiota in Weaned Piglets. Animals, 10.","DOI":"10.3390\/ani10040726"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Perry, T., Borowiec, A., Dicken, B., Fedorak, R., and Madsen, K. (2014). Murine Ileocolic Bowel Resection with Primary Anastomosis. J. Vis. Exp., e52106.","DOI":"10.3791\/52106-v"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1053\/gast.2001.27224","article-title":"Probiotic bacteria enhance murine and human intestinal epithelial barrier function","volume":"121","author":"Madsen","year":"2001","journal-title":"Gastroenterology"},{"key":"ref_26","first-page":"E272","article-title":"Tributyrin attenuates obesity-associated inflammation and insulin resistance in high-fat-fed mice","volume":"303","author":"Vinolo","year":"2012","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.chom.2016.03.004","article-title":"Depletion of Butyrate-Producing Clostridia from the Gut Microbiota Drives an Aerobic Luminal Expansion of Salmonella","volume":"19","author":"Zhang","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1001\/archinte.1972.03650040121011","article-title":"Bile Acid Malabsorption Caused by Ileal Resection","volume":"130","author":"Hofmann","year":"1972","journal-title":"Arch. Intern. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1016\/j.cell.2016.05.018","article-title":"The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites","volume":"165","author":"Kaiko","year":"2016","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.micinf.2016.09.004","article-title":"Hypoxia and inflammatory bowel disease","volume":"19","author":"Cummins","year":"2017","journal-title":"Microbes Infect."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/6\/2069\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:17:26Z","timestamp":1760163446000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/6\/2069"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,17]]},"references-count":30,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["nu13062069"],"URL":"https:\/\/doi.org\/10.3390\/nu13062069","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,17]]}}}