Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
Gut. 2013 Feb;62(2):220-6. doi: 10.1136/gutjnl-2011-300705. Epub 2012 Feb 16.
The gut microbiota is an environmental regulator of fat storage and adiposity. Whether the microbiota represents a realistic therapeutic target for improving metabolic health is unclear. This study explored two antimicrobial strategies for their impact on metabolic abnormalities in murine diet-induced obesity: oral vancomycin and a bacteriocin-producing probiotic (Lactobacillus salivarius UCC118 Bac(+)).
Male (7-week-old) C57BL/J6 mice (9-10/group) were fed a low-fat (lean) or a high-fat diet for 20 weeks with/without vancomycin by gavage at 2 mg/day, or with L. salivarius UCC118Bac(+) or the bacteriocin-negative derivative L. salivarius UCC118Bac(-) (each at a dose of 1×10(9) cfu/day by gavage). Compositional analysis of the microbiota was by 16S rDNA amplicon pyrosequencing.
Analysis of the gut microbiota showed that vancomycin treatment led to significant reductions in the proportions of Firmicutes and Bacteroidetes and a dramatic increase in Proteobacteria, with no change in Actinobacteria. Vancomycin-treated high-fat-fed mice gained less weight over the intervention period despite similar caloric intake, and had lower fasting blood glucose, plasma TNFα and triglyceride levels compared with diet-induced obese controls. The bacteriocin-producing probiotic had no significant impact on the proportions of Firmicutes but resulted in a relative increase in Bacteroidetes and Proteobacteria and a decrease in Actinobacteria compared with the non-bacteriocin-producing control. No improvement in metabolic profiles was observed in probiotic-fed diet-induced obese mice.
Both vancomycin and the bacteriocin-producing probiotic altered the gut microbiota in diet-induced obese mice, but in distinct ways. Only vancomycin treatment resulted in an improvement in the metabolic abnormalities associated with obesity thereby establishing that while the gut microbiota is a realistic therapeutic target, the specificity of the antimicrobial agent employed is critical.
肠道微生物群是脂肪储存和肥胖的环境调节剂。微生物群是否代表改善代谢健康的现实治疗靶点尚不清楚。本研究探索了两种抗菌策略对饮食诱导肥胖的小鼠代谢异常的影响：口服万古霉素和产细菌素的益生菌（唾液乳杆菌 UCC118 Bac(+)）。
雄性（7 周龄）C57BL/J6 小鼠（每组 9-10 只）分别用低脂肪（瘦）或高脂肪饮食喂养 20 周，并通过灌胃给予 2 毫克/天的万古霉素，或给予唾液乳杆菌 UCC118Bac(+)或细菌素阴性衍生物唾液乳杆菌 UCC118Bac(-)（每天通过灌胃给予 1×10(9)cfu）。通过 16S rDNA 扩增子焦磷酸测序分析微生物群的组成。
肠道微生物群分析表明，万古霉素治疗导致厚壁菌门和拟杆菌门的比例显著降低，变形菌门显著增加，而放线菌门没有变化。尽管热量摄入相似，但万古霉素治疗的高脂肪喂养小鼠在干预期间体重增加较少，空腹血糖、血浆 TNFα 和甘油三酯水平低于饮食诱导的肥胖对照组。产细菌素的益生菌对厚壁菌门的比例没有显著影响，但与非产细菌素的对照相比，导致拟杆菌门和变形菌门相对增加，放线菌门减少。在饮食诱导肥胖的小鼠中，益生菌喂养没有改善代谢谱。
万古霉素和产细菌素的益生菌都改变了饮食诱导肥胖的小鼠的肠道微生物群，但方式不同。只有万古霉素治疗导致与肥胖相关的代谢异常得到改善，从而确立了虽然肠道微生物群是一个现实的治疗靶点，但所使用的抗菌剂的特异性是关键的。
