Oxalobacter formigenes has been investigated for years due to its proposed ability to produce a secretagogue compound that initiates net intestinal oxalate secretion, thereby theoretically reducing circulating oxalate and risk of kidney stone formation. Strains which have been shown to exhibit this function in vivo across native tissue include the human strain, HC1, and the wild rat strain, OxWR. While previous work on these secretagogue-relevant strains has focused on profiling their metabolome and lipidome in vitro, efforts to characterize their influence on host intestinal mucosal biochemistry in vivo are yet to be reported. Much work has been done over the years with O. formigenes in relation to the secretagogue hypothesis, but it has never been clearly demonstrated that this microorganism is capable of inducing metabolic changes in native host tissue, which would be expected with the production of a transport-inducing compound. In this work, we show how the distal colonic mucosal metabolomic profile in a mouse model exhibited significant changes in the levels of a variety of metabolites as a result of oral gavage with O. formigenes HC1. Among these significant metabolites was nicotinic acid, an essential nutrient shown in past work to be produced in the gut by the native microbiome. Our finding that the in vivo biochemical state of the distal colon was altered with O. formigenes lends support to the secretagogue hypothesis and serves as a pioneering step in characterizing the biochemical interplay between O. formigenes and the mammalian host.

中文翻译：

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富氧草酸杆菌经口管饲后小鼠远端结肠黏膜的代谢组学改变

草酸富氧草酸已经被研究了很多年，因为它具有产生分泌促效剂化合物的能力，该化合物可引发肠道内草酸的净分泌，从而从理论上减少了草酸的循环和肾结石形成的风险。已显示在整个天然组织中体内表现出这种功能的菌株包括人类品系HC1和野生大鼠品系OxWR。尽管这些促分泌素相关菌株的先前研究重点是在体外对它们的代谢组和脂质组进行分析，但仍未报告表征其对体内宿主肠道粘膜生化的影响的努力。多年来，O。formigenes已完成许多工作关于促分泌素假说，但是从未清楚地证明这种微生物能够诱导天然宿主组织中的代谢变化，这可能是产生运输诱导化合物所期望的。在这项工作中，我们显示了在小鼠模型中远端结肠粘膜代谢组学谱图如何显示出与O. formigenes HC1一起进行口管灌胃，从而使各种代谢产物的水平发生了显着变化。烟酸是这些重要的代谢产物之一，烟碱酸是过去微生物在肠道中由天然微生物组产生的必需营养素。我们的发现表明，远端结肠的体内生化状态已被O. formigenes改变为促分泌素假说提供了支持，并成为表征产气壶菌和哺乳动物宿主之间生化相互作用的开创性步骤。