Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Veterans Health Administration-Tennessee Valley Healthcare System Geriatric Research Education Clinical Center (GRECC), HSR&D Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Clin Nutr ESPEN. 2021 Feb;41:436-438. doi: 10.1016/j.clnesp.2020.12.011. Epub 2021 Jan 7.
BACKGROUND & AIMS: Circulating levels of imidazole propionate (ImP), a microbial metabolite of histidine, were higher in participants with type 2 diabetes (T2D) compared to those without and also induced insulin resistance. We hypothesize that low intake of magnesium (Mg) and/or low body Mg status in humans may lead to low Mg concentrations in gut microbiota, and, in turn, elevated microbial production of ImP and increased levels of circulating ImP.
We tested this hypothesis in the Personalized Prevention of Colorectal Cancer Trial (PPCCT) (registered at clinicaltrials.gov as NCT01105169), a double-blind 2 × 2 factorial randomized controlled trial enrolling 240 participants at high risk of Mg deficiency. Among 68 participants (34 each in the treatment and placebo arms), we measured plasma metabolites using the untargeted Metabolon's global Precision Metabolomics™ LC-MS platform.
Mg treatment significantly reduced ImP by 39.9% compared to a 6.0% increase in the placebo arm (P = 0.02). We found the correlation coefficients were -0.12 (P = 0.32) and -0.31 (P < 0.01) between the change in ImP and changes in serum Mg and urinary Mg, respectively. In addition, we found Mg treatment increased circulating levels of propionic acid (InP) by 27.5% (P = 0.07) and reduced levels of glutarate by 17.9% (P = 0.04) compared to the placebo arm.
Further studies are needed to replicate these findings and to investigate whether Mg treatment specifically changes the production of ImP by microbiota. Also, future studies are warranted to confirm the effect of Mg treatment on glutarate and InP.
组氨酸的微生物代谢产物咪唑丙酸（ImP）在 2 型糖尿病（T2D）患者中的循环水平高于非糖尿病患者，并且还会诱导胰岛素抵抗。我们假设，人体内镁（Mg）的摄入量低和/或体内 Mg 状态低可能导致肠道微生物群中的 Mg 浓度降低，进而导致微生物产生更多的 ImP，循环 ImP 水平升高。
我们在个性化预防结直肠癌试验（PPCCT）中检验了这一假说（在 clinicaltrials.gov 上注册为 NCT01105169），这是一项双盲 2×2 因子随机对照试验，招募了 240 名有低镁风险的参与者。在 68 名参与者（治疗组和安慰剂组各 34 名）中，我们使用无靶向代谢组学的全球精准代谢组学 LC-MS 平台测量了血浆代谢物。
与安慰剂组的 6.0%增加相比，Mg 治疗组 ImP 显著降低了 39.9%（P=0.02）。我们发现 ImP 的变化与血清 Mg 和尿镁的变化之间的相关系数分别为-0.12（P=0.32）和-0.31（P<0.01）。此外，与安慰剂组相比，Mg 治疗组循环中丙酸（InP）的水平增加了 27.5%（P=0.07），戊二酸的水平降低了 17.9%（P=0.04）。
需要进一步的研究来复制这些发现，并研究 Mg 治疗是否会特异性地改变微生物群产生 ImP 的情况。此外，还需要进一步的研究来证实 Mg 治疗对戊二酸和 InP 的影响。
