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.
Methods: 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.
Results: 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.
Conclusions: 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.
Keywords: Imidazole propionate; Magnesium; Microbial metabolite; Randomized controlled trial; Type 2 diabetes.
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