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

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 decreased C. maltaromaticum, but not F. prausnitzii, compared with placebo in rectal swabs [-0.065 ± 0.511 (-6.54%) compared with 0.133 ± 0.503 (13.30%); adjusted P = 0.04]. The effect did not remain after false discovery rate correction. Mg treatment's effect on C. maltaromaticum in rectal swabs primarily appeared in females, and the treatment-genotype interaction remained significant.

Conclusions: In individuals with adequate TRPM7 function, Mg supplementation increases the abundance of C. maltaromaticum and F. prausnitzii.

Clinical trial registry: This trial was registered at clinicaltrials.gov as NCT04229992 (https://clinicaltrials.gov/study/NCT04229992?term=NCT04229992&rank=1). The parent study is registered as NCT03265483, and another relevant study is registered as NCT01105169.

Keywords: colorectal cancer; magnesium treatment; microbiome; precision medicine; randomized controlled trial.