Section of Gastroenterology, Division of Digestive Diseases and Nutrition, Department of Internal Medicine, Rush University Medical Center , Chicago, Illinois.
Department of Biochemistry, Rush University , Chicago, Illinois.
Am J Physiol Gastrointest Liver Physiol. 2018 Jan 1;314(1):G131-G141. doi: 10.1152/ajpgi.00103.2017. Epub 2017 Oct 26.
Recent studies suggest that circadian rhythms regulate intestinal barrier integrity, but it is not clear whether there are daily variations in barrier integrity. This study investigated daily variations in intestinal barrier integrity, including whether there are differences in alcohol-induced intestinal barrier dysfunction after an alcohol binge at different times of day and whether this is associated with concurrent liver injury. C57BL6/J male mice were fed a standard chow diet, an alcohol-containing liquid diet, or an alcohol control diet for 4 wk. During week 5 (i.e., on days 43-45), mice received three once-daily gavages of alcohol (6 g/kg) or the control (phosphate-buffered saline) at the same time each day. Immediately after the binge on the second day, intestinal permeability was assessed. Four hours after the third and final binge, mice were euthanized and tissue samples collected. The results demonstrated diet-specific and outcome-specific effects of time, alcohol, and/or time by alcohol interaction. Specifically, the alcohol binge robustly influenced markers of intestinal barrier integrity, and liver markers were robustly influenced by time of day. Only intestinal permeability (i.e., sucralose) demonstrated a significant effect of time and also showed a binge by time interaction, suggesting that the time of the alcohol binge influences colonic permeability. NEW & NOTEWORTHY This study investigated daily variations in intestinal barrier integrity, including whether there are differences in alcohol-induced intestinal barrier dysfunction after an alcohol binge at different times of day and whether this is associated with concurrent liver injury. We conclude that 1) alcohol binge significantly impacted markers of intestinal permeability, 2) time of day significantly affected liver outcomes, and 3) the time of day influenced colonic permeability.
最近的研究表明，昼夜节律调节肠道屏障的完整性，但目前尚不清楚肠道屏障的完整性是否存在每日变化。本研究调查了肠道屏障完整性的日变化，包括在一天中的不同时间点进行酒精 binge 是否会导致酒精引起的肠道屏障功能障碍的差异，以及这种差异是否与同时发生的肝损伤有关。C57BL6/J 雄性小鼠接受标准饲料、含酒精的液体饲料或酒精对照饮食 4 周。在第 5 周（即第 43-45 天），小鼠每天在同一时间接受三次单次灌胃酒精（6 g/kg）或对照（磷酸盐缓冲盐水）。在第二天 binge 后立即评估肠道通透性。第三次也是最后一次 binge 后 4 小时，处死小鼠并收集组织样本。结果表明，时间、酒精以及时间与酒精的相互作用对饮食和结果都有特异性影响。具体来说，酒精 binge 强烈影响肠道屏障完整性的标志物，而时间强烈影响肝脏标志物。只有肠道通透性（即蔗糖）表现出时间的显著影响，并且也表现出 binge 与时间的相互作用，表明酒精 binge 的时间会影响结肠通透性。本研究调查了肠道屏障完整性的日变化，包括在一天中的不同时间点进行酒精 binge 是否会导致酒精引起的肠道屏障功能障碍的差异，以及这种差异是否与同时发生的肝损伤有关。我们得出结论：1）酒精 binge 显著影响肠道通透性标志物，2）时间显著影响肝脏结果，3）时间影响结肠通透性。
