Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection.
Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection.
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DOI：
10.1038/ncomms4114
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发表时间：
2014
影响因子：
16.6
通讯作者：
Young VB
中科院分区：
文献类型：
--
作者：
Theriot CM;Koenigsknecht MJ;Carlson PE Jr;Hatton GE;Nelson AM;Li B;Huffnagle GB;Z Li J;Young VB
抗生素可以对胃肠道微生物群具有显著和持久的影响，降低对包括艰难梭菌在内的病原体的定殖抗性。在这里，我们表明抗生素治疗诱导肠道微生物群落和易受C.艰难感染次级胆汁酸、葡萄糖、游离脂肪酸和二肽的水平降低，而初级胆汁酸和糖醇的水平增加，反映了改变的肠道微生物组的代谢活性改变。体外和离体分析表明，C.艰难梭菌可以利用特定的代谢物，这些代谢物在使用抗生素后在小鼠肠道中变得更丰富，包括用于发芽的初级胆汁酸牛磺胆酸盐，以及用于生长的碳源甘露醇、果糖、山梨醇、棉子糖和水苏糖。我们的研究结果表明，益生菌介导的肠道微生物组的改变将全球代谢谱转化为有利于C。难以萌发和生长。
Antibiotics can have significant and long lasting effects on the gastrointestinal tract microbiota, reducing colonization resistance against pathogens including Clostridium difficile. Here we show that antibiotic treatment induces substantial changes in the gut microbial community and in the metabolome of mice susceptible to C. difficile infection. Levels of secondary bile acids, glucose, free fatty acids, and dipeptides decrease, whereas those of primary bile acids and sugar alcohols increase, reflecting the modified metabolic activity of the altered gut microbiome. In vitro and ex vivo analyses demonstrate that C. difficile can exploit specific metabolites that become more abundant in the mouse gut after antibiotics, including primary bile acid taurocholate for germination, and carbon sources mannitol, fructose, sorbitol, raffinose and stachyose for growth. Our results indicate that antibiotic-mediated alteration of the gut microbiome converts the global metabolic profile to one that favors C. difficile germination and growth.