Division of Cardiothoracic Surgery, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA.
FASEB J. 2012 Apr;26(4):1727-35. doi: 10.1096/fj.11-197921. Epub 2012 Jan 12.
Signals from the intestinal microbiota are important for normal host physiology; alteration of the microbiota (dysbiosis) is associated with multiple disease states. We determined the effect of antibiotic-induced intestinal dysbiosis on circulating cytokine levels and severity of ischemia/reperfusion injury in the heart. Treatment of Dahl S rats with a minimally absorbed antibiotic vancomycin, in the drinking water, decreased circulating leptin levels by 38%, resulted in smaller myocardial infarcts (27% reduction), and improved recovery of postischemic mechanical function (35%) as compared with untreated controls. Vancomycin altered the abundance of intestinal bacteria and fungi, measured by 16S and 18S ribosomal DNA quantity. Pretreatment with leptin (0.12 μg/kg i.v.) 24 h before ischemia/reperfusion abolished cardioprotection produced by vancomycin treatment. Dahl S rats fed the commercially available probiotic product Goodbelly, which contains the leptin-suppressing bacteria Lactobacillus plantarum 299v, also resulted in decreased circulating leptin levels by 41%, smaller myocardial infarcts (29% reduction), and greater recovery of postischemic mechanical function (23%). Pretreatment with leptin (0.12 μg/kg i.v.) abolished cardioprotection produced by Goodbelly. This proof-of-concept study is the first to identify a mechanistic link between changes in intestinal microbiota and myocardial infarction and demonstrates that a probiotic supplement can reduce myocardial infarct size.
肠道微生物群的信号对于正常的宿主生理功能很重要；微生物群的改变（失调）与多种疾病状态有关。我们确定了抗生素诱导的肠道失调对循环细胞因子水平和心脏缺血/再灌注损伤严重程度的影响。在饮用水中用一种吸收较少的抗生素万古霉素处理 Dahl S 大鼠，使循环瘦素水平降低了 38%，导致心肌梗死面积减小（减少 27%），并改善了缺血后机械功能的恢复（增加 35%），与未治疗的对照组相比。万古霉素改变了肠道细菌和真菌的丰度，通过 16S 和 18S 核糖体 DNA 量来衡量。缺血/再灌注前 24 小时静脉注射瘦素（0.12 μg/kg）预处理消除了万古霉素治疗产生的心脏保护作用。用含有抑制瘦素的细菌植物乳杆菌 299v 的市售益生菌产品 Goodbelly 喂养 Dahl S 大鼠，也使循环瘦素水平降低了 41%，心肌梗死面积减小（减少 29%），缺血后机械功能恢复更好（增加 23%）。静脉注射瘦素（0.12 μg/kg）预处理消除了 Goodbelly 产生的心脏保护作用。这项概念验证研究首次确定了肠道微生物群变化与心肌梗死之间的机制联系，并表明益生菌补充剂可以减少心肌梗死的面积。
