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经口灌胃给予……后小鼠远端结肠黏膜的代谢组学改变

Metabolomic Alteration in the Mouse Distal Colonic Mucosa after Oral Gavage with .

作者信息

Chamberlain Casey A, Hatch Marguerite, Garrett Timothy J

机构信息

Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.

出版信息

Metabolites. 2020 Oct 13;10(10):405. doi: 10.3390/metabo10100405.

Abstract

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 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 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 lends support to the secretagogue hypothesis and serves as a pioneering step in characterizing the biochemical interplay between and the mammalian host.

摘要

由于其具有产生一种促分泌素化合物的能力,该化合物可引发肠道草酸盐净分泌,从而理论上降低循环草酸盐水平和肾结石形成风险,因此多年来一直受到研究。已证明在天然组织中体内表现出这种功能的菌株包括人类菌株HC1和野生大鼠菌株OxWR。虽然之前对这些与促分泌素相关的菌株的研究主要集中在体外分析它们的代谢组和脂质组,但尚未有关于它们对宿主肠道黏膜生物化学体内影响的表征工作的报道。多年来围绕促分泌素假说开展了大量工作,但从未明确证明这种微生物能够在天然宿主组织中诱导代谢变化,而这是产生一种诱导转运化合物时所预期的。在这项工作中,我们展示了在小鼠模型中,经口灌胃HC1后,远端结肠黏膜代谢组学谱如何在多种代谢物水平上表现出显著变化。这些显著的代谢物中包括烟酸,过去的研究表明它是一种由天然微生物群在肠道中产生的必需营养素。我们关于远端结肠体内生化状态因HC1而改变的发现支持了促分泌素假说,并作为表征HC1与哺乳动物宿主之间生化相互作用的开创性一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faed/7650779/eb30caad0c13/metabolites-10-00405-g001.jpg

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