Metabolomic and lipidomic characterization of Oxalobacter formigenes strains HC1 and OxWR by UHPLC-HRMS
Metabolomic and lipidomic characterization of Oxalobacter formigenes strains HC1 and OxWR by UHPLC-HRMS
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DOI：
10.1007/s00216-019-01639-y
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发表时间：
2019-07-01
影响因子：
4.3
通讯作者：
Garrett, Timothy J.
中科院分区：
文献类型：
--
作者：
Chamberlain, Casey A.;Hatch, Marguerite;Garrett, Timothy J.
草酸盐疾病，如肾结石和原发性高尿酸血症，影响了美国人口的很大一部分，治疗选择有限。产草酸杆菌是哺乳动物肠道中的一种专性草酸营养细菌，由于其能够降解外源性（饮食）和内源性（代谢）草酸盐，降低高尿酸/高尿酸血症的风险，因此作为潜在的益生菌或治疗性治疗草酸盐相关疾病引起了极大的兴趣。虽然所有的草酸营养菌降解膳食草酸盐，Oxalactiniformigenes是唯一的物种显示启动肠道草酸盐分泌，利用内源性，循环草酸盐消耗。有证据表明，草酸钙调节草酸转运蛋白在肠上皮细胞使用一个身份不明的分泌的生物活性化合物，但这种功能的机制仍然难以捉摸。了解草酸盐与宿主肠上皮细胞之间的生化关系对于这种微生物作为草酸盐疾病的潜在治疗方法的进展至关重要。这项研究包括草酸盐形成基因的代谢组和脂质组的第一次分析，特别是人类菌株HCl和大鼠菌株OxWR，迄今为止仅有的两种菌株显示启动天然肠道上皮细胞的净肠道草酸盐分泌。本研究采用非靶向和靶向代谢组学和脂质组学方法，利用超高效液相色谱-质谱法进行。我们报告我们的研究结果，这些菌株的代谢谱，虽然在很大程度上保守，显示出显着差异，在他们的许多化合物的表达。还检测到几种菌株特异性特征。讨论的是在整个代谢谱的趋势，以及在个别功能，无论是确定和未确定的。
Diseases of oxalate, such as nephrolithiasis and primary hyperoxaluria, affect a significant portion of the US population and have limited treatment options. Oxalobacter formigenes, an obligate oxalotrophic bacterium in the mammalian intestine, has generated great interest as a potential probiotic or therapeutic treatment for oxalate-related conditions due to its ability to degrade both exogenous (dietary) and endogenous (metabolic) oxalate, lowering the risk of hyperoxaluria/hyperoxalemia. Although all oxalotrophs degrade dietary oxalate, Oxalobacter formigenes is the only species shown to initiate intestinal oxalate secretion to draw upon endogenous, circulating oxalate for consumption. Evidence suggests that Oxalobacter regulates oxalate transport proteins in the intestinal epithelium using an unidentified secreted bioactive compound, but the mechanism of this function remains elusive. It is essential to gain an understanding of the biochemical relationship between Oxalobacter and the host intestinal epithelium for this microbe to progress as a potential remedy for oxalate diseases. This investigation includes the first profiling of the metabolome and lipidome of Oxalobacter formigenes, specifically the human strain HC1 and rat strain OxWR, the only two strains shown thus far to initiate net intestinal oxalate secretion across native gut epithelia. This study was performed using untargeted and targeted metabolomics and lipidomics methodologies utilizing ultra-high-performance liquid chromatography-mass spectrometry. We report our findings that the metabolic profiles of these strains, although largely conserved, show significant differences in their expression of many compounds. Several strain-specific features were also detected. Discussed are trends in the whole metabolic profile as well as in individual features, both identified and unidentified.