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Magnesium treatment increases gut microbiome synthesizing vitamin D and inhibiting colorectal cancer: results from a double-blind precision-based randomized placebo-controlled trial

Elizabeth Sun, Xiangzhu Zhu, R. M. Ness, Harvey J Murff, Shan Sun, Chang Yu, Lei Fan, M. Azcarate-Peril et al.

American Journal of Clinical Nutrition, 2025

240 participants · 7 citations

Abstract

Background Carnobacterium maltaromaticum and Faecalibacterium prausnitzii induce de novo gut synthesis of vitamin D to inhibit colorectal carcinogenesis in mice. Magnesium (Mg) treatment increases circulating vitamin D, and Mg homeostasis is dependent on TRPM7 genotype. Objectives We hypothesize that Mg treatment increases gut C. maltaromaticum and F. prausnitzii, and the effect differs by TRPM7 polymorphism. Methods The Personalized Prevention of Colorectal Cancer Trial is a double-blind, precision-based randomized controlled trial with 240 participants randomly assigned to both treatment and TRPM7 genotype. Stool, rectal swabs, and rectal mucosa were collected. Results Of 239 participants who completed the trial, 226 with valid microbiome data were analyzed (treatment n = 112, placebo n = 114). The interaction between treatment and TRPM7 genotype was only significant for C. maltaromaticum (P = 0.001) and F. prausnitzii (P = 0.02) in rectal swabs. In a stratified analysis by TRPM7 genotype without the missense variant, Mg treatment compared with placebo significantly increased abundance of C. maltaromaticum (0.217 ± 0.615 (23.01%) compared with –0.065 ± 0.588 (–6.30%); P = 0.006) and F. prausnitzii (0.105 ± 0.817 (2.13%) compared with –0.095 ± 0.856 (–1.92%); P = 0.04) in rectal swabs. The effect on C. maltaromaticum remained after multiple comparisons (Q = 0.05 for C. maltaromaticum across all sample types and genotypes). In those with the TRPM7 missense variant, Mg…

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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 240 participants or records.

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