Timing of Tributyrin Supplementation Differentially Modulates Gastrointestinal Inflammation and Gut Microbial Recolonization Following Murine Ileocecal Resection

Nutrients

Heekuk Park¹  Aducio Thiesen²  Naomi Hotte³  Daniel Birch⁴  Michael Laffin⁴  Jerry Dang⁴  Valentin Mocanu⁴  Haili Wang⁴  Karen Madsen⁵ 

[1] Columbia University Medical Center, New York, NY 10032, USA;Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2R3, Canada;Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada;Department of Surgery, University of Alberta, Edmonton, AB T6G 2R3, Canada;Division of Gastroenterology, University of Alberta, Edmonton, AB T6G 2R3, Canada;

关键词: tributyrin;    inflammatory bowel disease;    ileocecal resection;    Crohn’s disease;    microbiome;   

DOI  :  10.3390/nu13062069

来源: DOAJ

【 摘 要 】

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 8–15 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-1β (p = 0.09), IL-6 (p = 0.03), and TNF-α (p < 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-α (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.

【 授权许可】

Unknown