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.

中文翻译：

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UHPLC-HRMS对富氧草酸杆菌HC1和OxWR的代谢组学和脂质组学表征。

草酸盐病，例如肾结石病和原发性高草酸尿症，影响了美国人口的很大一部分，并且治疗选择有限。草酸富氧草酸是哺乳动物肠道中一种专性的草酸营养细菌，由于它具有降解外源性（饮食）和内源性（代谢）草酸盐的能力，因此作为草酸盐相关疾病的潜在益生菌或治疗剂引起了极大的兴趣，从而降低了患草酸的风险。高草酸尿症/高草酸血症。尽管所有草酸营养物质都降解膳食草酸，但是，草酸变形酶是唯一能够启动肠道草酸分泌以吸收内源性循环草酸以供食用的物种。有证据表明草酸杆菌通过使用一种未知的分泌的生物活性化合物调节肠道上皮中的草酸转运蛋白，但该功能的机制仍然难以捉摸。必须了解草酸杆菌和宿主肠道上皮之间的生化关系，才能使该微生物作为草酸盐疾病的潜在治疗手段而发展。该研究包括草酸杆菌的代谢组和脂质组的首次分析，特别是人类菌株HC1和大鼠菌株OxWR，是迄今显示的仅有的两个菌株，可在整个天然肠上皮细胞中引发草酸小肠的净分泌。这项研究是使用非靶向和靶向代谢组学和脂质组学方法论，利用超高效液相色谱-质谱联用技术进行的。我们报告了我们的发现，尽管这些菌株的代谢谱在很大程度上是保守的，但它们在许多化合物的表达中显示出显着差异。还检测到了几种菌株特有的特征。讨论了整个代谢过程以及个体特征（已识别和未识别）的趋势。