*Department of Pharmacology, School of Pharmacy, University of Granada, Granada, Spain.
‡CIBER-EHD, Department of Pharmacology, Center for Biomedical Research, University of Granada, Granada, Spain.
Clin Sci (Lond). 2014 Jul;127(1):33-45. doi: 10.1042/CS20130339.
Obesity is associated with intestine dysbiosis and is characterized by a low-grade inflammatory status, which affects vascular function. In the present study, we evaluated the effects of a probiotic with immunomodulatory properties, Lactobacillus coryniformis CECT5711, in obese mice fed on an HFD (high-fat diet). The probiotic treatment was given for 12 weeks, and it did not affect the weight evolution, although it reduced basal glycaemia and insulin resistance. L. coryniformis administration to HFD-induced obese mice induced marked changes in microbiota composition and reduced the metabolic endotoxaemia as it decreased the LPS (lipopolysaccharide) plasma level, which was associated with a significant improvement in gut barrier disruption. Furthermore, it lowered TNFα (tumour necrosis factor α) expression in liver, improving the inflammatory status, and thus the glucose metabolism. Additionally, the probiotic reversed the endothelial dysfunction observed in obese mice when endothelium- and NO (nitric oxide)-dependent vasodilatation induced by acetylcholine in aortic rings was studied. It also restored the increased vessel superoxide levels observed in obese mice, by reducing NADPH oxidase activity and increasing antioxidant enzymes. Moreover, chronic probiotic administration for 2 weeks also improved endothelial dysfunction and vascular oxidative stress induced by in vivo administration of LPS in control mice fed on a standard chow diet. The results of the present study demonstrate an endothelial-protective effect of L. coryniformis CECT5711 in obese mice by increasing NO bioavailability, suggesting the therapeutic potential of this gut microbiota manipulation to prevent vasculopathy in obesity.
肥胖与肠道菌群失调有关,其特征为低度炎症状态,这会影响血管功能。在本研究中,我们评估了具有免疫调节特性的益生菌 Lactobacillus coryniformis CECT5711 对高脂饮食(HFD)喂养肥胖小鼠的影响。益生菌治疗持续了 12 周,它并没有影响体重变化,尽管它降低了基础血糖和胰岛素抵抗。L. coryniformis 对 HFD 诱导的肥胖小鼠的给药导致了微生物群组成的显著变化,并降低了代谢性内毒素血症,因为它降低了 LPS(脂多糖)的血浆水平,这与肠道屏障破坏的显著改善相关。此外,它降低了肝脏中 TNFα(肿瘤坏死因子 α)的表达,改善了炎症状态,从而改善了葡萄糖代谢。此外,当研究在肥胖小鼠中诱导的乙酰胆碱引起的主动脉环内皮和 NO(一氧化氮)依赖性血管舒张时,益生菌逆转了肥胖小鼠中观察到的内皮功能障碍。它还通过降低 NADPH 氧化酶活性和增加抗氧化酶来恢复肥胖小鼠中观察到的增加的血管超氧化物水平。此外,在标准饮食喂养的对照小鼠中,连续给予益生菌 2 周也改善了由体内给予 LPS 诱导的内皮功能障碍和血管氧化应激。本研究的结果表明,L. coryniformis CECT5711 在肥胖小鼠中具有内皮保护作用,通过增加 NO 的生物利用度来实现,这表明这种肠道微生物群操纵在预防肥胖症中的血管病变方面具有治疗潜力。