Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 6500017, Japan.
Division of Applied Life Science, Graduate School of Agriculture, Kyoto University, Kyoto, 6068502, Japan.
Sci Rep. 2020 Aug 3;10(1):13009. doi: 10.1038/s41598-020-69983-z.
Faecal lipopolysaccharides (LPS) have attracted attention as potent elements to explain a correlation between the gut microbiota and cardiovascular disease (CVD) progression. However, the underlying mechanism of how specific gut bacteria contribute to faecal LPS levels remains unclear. We retrospectively analysed the data of 92 patients and found that the abundance of the genus Bacteroides was significantly and negatively correlated with faecal LPS levels. The controls showed a higher abundance of Bacteroides than that in the patients with CVD. The endotoxin units of the Bacteroides LPS, as determined by the limulus amoebocyte lysate (LAL) tests, were drastically lower than those of the Escherichia coli LPS; similarly, the Bacteroides LPS induced relatively low levels of pro-inflammatory cytokine production and did not induce sepsis in mice. Fermenting patient faecal samples in a single-batch fermentation system with Bacteroides probiotics led to a significant increase in the Bacteroides abundance, suggesting that the human gut microbiota could be manipulated toward decreasing the faecal LPS levels. In the clinical perspective, Bacteroides decrease faecal LPS levels because of their reduced LAL activity; therefore, increasing Bacteroides abundance might serve as a novel therapeutic approach to prevent CVD via reducing faecal LPS levels and suppressing immune responses.
粪便脂多糖(LPS)作为解释肠道微生物群与心血管疾病(CVD)进展之间相关性的有力因素而受到关注。然而,特定肠道细菌如何有助于粪便 LPS 水平的潜在机制尚不清楚。我们回顾性分析了 92 名患者的数据,发现拟杆菌属的丰度与粪便 LPS 水平呈显著负相关。对照组中拟杆菌属的丰度明显高于 CVD 患者。通过鲎变形细胞溶解物(LAL)试验测定的拟杆菌 LPS 的内毒素单位明显低于大肠杆菌 LPS;同样,拟杆菌 LPS 诱导的促炎细胞因子产生水平相对较低,并且不会在小鼠中引起败血症。在单批发酵系统中用拟杆菌益生菌发酵患者粪便样本会导致拟杆菌属丰度显著增加,这表明可以通过调节肠道微生物群来降低粪便 LPS 水平。从临床角度来看,拟杆菌属由于其 LAL 活性降低而降低粪便 LPS 水平;因此,增加拟杆菌属的丰度可能成为一种通过降低粪便 LPS 水平和抑制免疫反应来预防 CVD 的新的治疗方法。