An Integrated Metabolomic and Microbiome Analysis Identified Specific Gut Microbiota Associated with Fecal Cholesterol and Coprostanol in Clostridium difficile Infection.
An Integrated Metabolomic and Microbiome Analysis Identified Specific Gut Microbiota Associated with Fecal Cholesterol and Coprostanol in Clostridium difficile Infection.
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DOI：
10.1371/journal.pone.0148824
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Wang GP
中科院分区：
文献类型：
--
作者：
Antharam VC;McEwen DC;Garrett TJ;Dossey AT;Li EC;Kozlov AN;Mesbah Z;Wang GP
艰难梭菌感染（CDI）的特征是肠道微生物群的生态失调和粪便代谢组的严重紊乱。然而，特定肠道微生物对艰难梭菌相关肠道微生物群中粪便代谢物的贡献仍然知之甚少。采用气相色谱-质谱（GC-MS）和16S rRNA深度测序，我们分析了艰难梭菌感染（n = 7）和健康对照（n = 6）纵向获得的粪便样本的代谢组和微生物组。从155种粪便代谢物中，我们鉴定出两种甾醇代谢物与胆固醇和coprostanol的匹配度为b> 95%，可以显著区分与艰难梭菌相关的肠道微生物群和健康微生物群。通过将粪便提取物中胆固醇和粪前列醇的水平与16S rRNA测序确定的2395个细菌操作分类单位（otu）进行关联，我们鉴定出63个与高水平粪前列醇相关的otu和2个与低水平粪前列醇相关的otu。利用指示种分析（ISA）， 63种与coprostanol相关的细菌中有31种与健康相关，2种Veillonella与低coprostanol水平相关，与CDI密切相关。这65个细菌分类群可聚为12个亚群落，每个亚群落包含一个相互共存的生物联合体。我们的研究确定了63种人类肠道微生物与降低胆固醇的活动有关。鉴于肠道细菌在降低和消除胃肠道胆固醇方面的重要性，这些结果支持了最近的发现，即肠道微生物群可能在宿主脂质代谢中发挥重要作用。
Clostridium difficile infection (CDI) is characterized by dysbiosis of the intestinal microbiota and a profound derangement in the fecal metabolome. However, the contribution of specific gut microbes to fecal metabolites in C. difficile-associated gut microbiome remains poorly understood. Using gas-chromatography mass spectrometry (GC-MS) and 16S rRNA deep sequencing, we analyzed the metabolome and microbiome of fecal samples obtained longitudinally from subjects with Clostridium difficile infection (n = 7) and healthy controls (n = 6). From 155 fecal metabolites, we identified two sterol metabolites at >95% match to cholesterol and coprostanol that significantly discriminated C. difficile-associated gut microbiome from healthy microbiota. By correlating the levels of cholesterol and coprostanol in fecal extracts with 2,395 bacterial operational taxonomic units (OTUs) determined by 16S rRNA sequencing, we identified 63 OTUs associated with high levels of coprostanol and 2 OTUs correlated with low coprostanol levels. Using indicator species analysis (ISA), 31 of the 63 coprostanol-associated bacteria correlated with health, and two Veillonella species were associated with low coprostanol levels that correlated strongly with CDI. These 65 bacterial taxa could be clustered into 12 sub-communities, with each community containing a consortium of organisms that co-occurred with one another. Our studies identified 63 human gut microbes associated with cholesterol-reducing activities. Given the importance of gut bacteria in reducing and eliminating cholesterol from the GI tract, these results support the recent finding that gut microbiome may play an important role in host lipid metabolism.