Yamashiro Kazuo, Tanaka Ryota, Urabe Takao, Ueno Yuji, Yamashiro Yuichiro, Nomoto Koji, Takahashi Takuya, Tsuji Hirokazu, Asahara Takashi, Hattori Nobutaka
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
Department of Neurology, Juntendo University Urayasu Hospital, Chiba, Japan.
PLoS One. 2017 Feb 6;12(2):e0171521. doi: 10.1371/journal.pone.0171521. eCollection 2017.
The role of metabolic diseases in ischemic stroke has become a primary concern in both research and clinical practice. Increasing evidence suggests that dysbiosis is associated with metabolic diseases. The aim of this study was to investigate whether the gut microbiota, as well as concentrations of organic acids, the major products of dietary fiber fermentation by the gut microbiota, are altered in patients with ischemic stroke, and to examine the association between these changes and host metabolism and inflammation. We analyzed the composition of the fecal gut microbiota and the concentrations of fecal organic acids in 41 ischemic stroke patients and 40 control subjects via 16S and 23S rRNA-targeted quantitative reverse transcription (qRT)-PCR and high-performance liquid chromatography analyses, respectively. Multivariable linear regression analysis was subsequently performed to evaluate the relationships between ischemic stroke and bacterial counts and organic acid concentrations. Correlations between bioclinical markers and bacterial counts and organic acids concentrations were also evaluated. Although only the bacterial counts of Lactobacillus ruminis were significantly higher in stroke patients compared to controls, multivariable analysis showed that ischemic stroke was independently associated with increased bacterial counts of Atopobium cluster and Lactobacillus ruminis, and decreased numbers of Lactobacillus sakei subgroup, independent of age, hypertension, and type 2 diabetes. Changes in the prevalence of Lactobacillus ruminis were positively correlated with serum interleukin-6 levels. In addition, ischemic stroke was associated with decreased and increased concentrations of acetic acid and valeric acid, respectively. Meanwhile, changes in acetic acid concentrations were negatively correlated with the levels of glycated hemoglobin and low-density lipoprotein cholesterol, whereas changes in valeric acid concentrations were positively correlated with the level of high sensitivity C-reactive protein and with white blood cell counts. Together, our findings suggest that gut dysbiosis in patients with ischemic stroke is associated with host metabolism and inflammation.
代谢性疾病在缺血性卒中中的作用已成为研究和临床实践中的主要关注点。越来越多的证据表明，肠道菌群失调与代谢性疾病有关。本研究的目的是调查缺血性卒中患者的肠道微生物群以及肠道微生物群发酵膳食纤维的主要产物有机酸的浓度是否发生改变，并检查这些变化与宿主代谢和炎症之间的关联。我们分别通过靶向16S和23S rRNA的定量逆转录（qRT）-PCR和高效液相色谱分析，分析了41例缺血性卒中患者和40例对照受试者的粪便肠道微生物群组成和粪便有机酸浓度。随后进行多变量线性回归分析，以评估缺血性卒中和细菌计数以及有机酸浓度之间的关系。还评估了生物临床标志物与细菌计数和有机酸浓度之间的相关性。尽管与对照组相比，卒中患者中仅瘤胃乳杆菌的细菌计数显著更高，但多变量分析表明，缺血性卒中与阿托波菌属簇和瘤胃乳杆菌的细菌计数增加以及清酒乳杆菌亚组数量减少独立相关，与年龄、高血压和2型糖尿病无关。瘤胃乳杆菌患病率的变化与血清白细胞介素-6水平呈正相关。此外，缺血性卒中分别与乙酸浓度降低和戊酸浓度升高有关。同时，乙酸浓度的变化与糖化血红蛋白和低密度脂蛋白胆固醇水平呈负相关，而戊酸浓度的变化与高敏C反应蛋白水平和白细胞计数呈正相关。总之，我们的研究结果表明，缺血性卒中患者的肠道菌群失调与宿主代谢和炎症有关。
