Antibiotic-induced gut metabolome and microbiome alterations increase the susceptibility to Candida albicans colonization in the gastrointestinal tract
Antibiotic-induced gut metabolome and microbiome alterations increase the susceptibility to Candida albicans colonization in the gastrointestinal tract
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DOI：
10.1093/femsec/fiz187
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发表时间：
2020-01-01
影响因子：
4.2
通讯作者：
Thangamani, Shankar
中科院分区：
文献类型：
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作者：
Gutierrez, Daniel;Weinstock, Anthony;Thangamani, Shankar
抗生素引起的肠道生态系统的改变增加了对白色念珠菌的易感性，但其中涉及的机制仍不清楚。在这里，我们显示了用广谱抗生素头孢哌酮治疗的小鼠促进了白色念珠菌的生长、形态发生和胃肠道(GI)定植。利用代谢组学方法，我们发现头孢哌酮治疗的小鼠盲肠代谢环境显示出明显的肠道代谢产物改变。在易受白色念珠菌感染的抗生素治疗的小鼠中，碳水化合物、糖醇和初级胆汁酸的水平上升，而羧酸和次级胆汁酸的水平下降。此外，通过体外实验，我们证实了碳水化合物、糖醇和初级胆汁酸促进白色念珠菌的生长和形态发生，而羧酸和次级胆汁酸则抑制白色念珠菌的生长和形态发生。此外，在这项研究中，我们报告了与肠道微生物区系变化相关的肠道代谢物水平的变化。综上所述，我们的体内和体外结果表明，头孢哌酮诱导的代谢组和微生物组的改变有利于白色念珠菌的生长和形态发生，并可能在白色念珠菌的胃肠道定植中发挥重要作用。
Antibiotic-induced alterations in the gut ecosystem increases the susceptibility to Candida albicans, yet the mechanisms involved remains poorly understood. Here we show that mice treated with the broad-spectrum antibiotic cefoperazone promoted the growth, morphogenesis and gastrointestinal (GI) colonization of C. albicans. Using metabolomics, we revealed that the cecal metabolic environment of the mice treated with cefoperazone showed a significant alteration in intestinal metabolites. Levels of carbohydrates, sugar alcohols and primary bile acids increased, whereas carboxylic acids and secondary bile acids decreased in antibiotic treated mice susceptible to C. albicans. Furthermore, using in-vitro assays, we confirmed that carbohydrates, sugar alcohols and primary bile acids promote, whereas carboxylic acids and secondary bile acids inhibit the growth and morphogenesis of C. albicans. In addition, in this study we report changes in the levels of gut metabolites correlated with shifts in the gut microbiota. Taken together, our in-vivo and in-vitro results indicate that cefoperazone-induced metabolome and microbiome alterations favor the growth and morphogenesis of C. albicans, and potentially play an important role in the GI colonization of C. albicans.